Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.

Background and Objectives: Clinical trials are a critical step in the development of new medicines and medical devices, testing the efficacy and safety of new treatment regimens. However, if the results of clinical trials are not made public, the evidence base on interventions is incomplete and possibly distorted, which lead to suboptimal treatment choices and negatively affect public health. This study analyses and contrasts the laws and regulations governing clinical trial registration and reporting in China and the United States. Methods: We used desk research to compile, assess and compare current laws, regulations, compliance patterns, and enforcement mechanisms and actions in China and the United States (U.S.). Policy documents were downloaded from Chinese and U.S. government websites. A spreadsheet analysis was utilized for direct comparison. Results: Both China and the U.S. have laws and regulations governing clinical trial registration and reporting. Chinese legislation covers a broader range of trials. In the U.S. trial results must be disclosed to both the national regulator and the public, while Chinese law mandates disclosure to the regulator alone. Cross-country comparisons of regulatory compliance by trial sponsors are impossible due to the opacity of the Chinese data platform. Neither country effectively ensures that all clinical trial results are made public as required by the Declaration of Helsinki and recommended by the WHO. Interpretation: While neither country is perfect, both may be able to learn from each other. There is a major gap in the literature regarding the extent of non-publication of clinical trial results by sponsors operating in China.

Hemoglobin is one of the proteins that are more susceptible to S-glutathionylation and the levels of its modified form, glutathionyl hemoglobin, increase in several human pathological conditions. The scope of the present review is to provide knowledge about how hemoglobin is subjected to be S-glutathionylated and how this modification affects its functionality. The different diseases that showed increased levels of glutathionyl hemoglobin and the methods used for its quantification in clinical investigations will be also outlined. Since there is a growing need for precise and reliable methods of markers of oxidative stress in human blood, this review highlights how glutathionyl hemoglobin is more and more emerging as a good indicator of severe oxidative stress but also as a key pathogenic factor in several diseases.

In order to harness the potential of mobile technologies to enhance the quality of clinical research, it is critical to first understand how to engage patients and research sites when planning and conducting mobile clinical trials. The Clinical Trials Transformation Initiative has developed the first comprehensive, evidence-based set of recommendations for incorporating patient and site perspectives in mobile clinical trials, which can aid in engaging stakeholders, addressing site challenges, and maximizing value for participants.

Management of Juvenile idiopathic arthritis (JIA) has improved tremendously in recent years due to the introduction of new drug therapies but remains complex also in terms of non-pharmaceutical issues. In order to determine the direction of scientific progress by characterizing the current spectrum of ongoing clinical research in JIA, we analyzed all ongoing studies in the field of JIA registered in clinicaltrials.gov and clinicaltrialsregister.eu concerning sponsoring, enrollment, duration, localization, and particularly objectives. Close of database was 7 January 2021. After identifying doubled-registered studies, N=72 went into further analysis. Of these, 61.1% were academia-sponsored and 37.5% by pharma industry. The majority of studies was of interventional type (77.8%), while others (22.2%) were observational. Median planned enrollments were 100 participants (interventional studies) and 175 participants (observational studies), respectively. Duration differed remarkably from one month to more than 15 years with a median of 42.5 months. 61.1% of studies were located in a single country, 38.9% were in several. Europe and North America clearly dominated study localizations. Study objectives were DMARDs (56.9%), followed by diagnostics and disease activity measurement (18.1%), and medication other than DMARD (12.5%), besides others. Studies on DMARDs were mainly sponsored by industry, predominantly interventional studies on established and novel biologics, with several on specific issues like systemic JIA and others. The spectrum of registered studies is currently centered on drug therapy and diagnostics, while other issues in JIA play a subordinated role.

All the available botulinum type A neurotoxins for clinical uses are of A1 subtype. We developed a subtype A2 low molecular weight (150kD) neurotoxin (A2NTX), with less spread and faster entry into the motor nerve terminal than A1 in vitro and in vivo. Preliminary clinical studies showed its efficacy superior to A1 toxins. We conducted an open study exploring its safety and tolerability profile in comparison with A1LL (onabotulinumtoxinA) and low molecular weight (150kD) A1 neurotoxin (A1NTX). Those who had been using A1LL (n=90; 50-360 mouse LD50 units) or A1NTX (n=30; 50-580 units) were switched to A2NTX (n=120; 25-600 units) from 2010 till 2018 (number of sessions ~ 27, cumulative doses ~11,640 units per patient). Adverse events for A2NTX included weakness (n=1, ascribed to alcoholic polyneuropathy), dysphagia (1), local weakness (4), spread to other muscles (1), whereas those for A1LL or A1NTX comprised weakness (n=2, A1NTX), dysphagia (8), ptosis (6), local weakness (7) and spread to other muscles (15). After injections, 89 out of 120 patients preferred A2NTX to A1 for the successive sessions. The present study demonstrated that A2NTX had the clinical safety up to the dose of 500 units, and was well tolerated compared to A1 toxins.

The Swiss Personalized Health Network (SPHN) is a Swiss research infrastructure initiative that aims to facilitate the exchange of health-related data in a FAIR manner. The SPHN Dataset and SPHN RDF Schema form an essential part of the SPHN Semantic Interoperability Framework, which currently covers mostly clinical routine data. To facilitate the integration of omics data produced by the SPHN National Data Streams, a genomics extension was developed. This was done in close collaboration with clinicians, researchers, bioinformaticians, and data managers, from Swiss university hospitals, academic research groups and the omics platforms. Here, we present the genomics extension of the SPHN RDF Schema, which can be used to semantically describe genomics experiments and covers both clinical and research domains. The schema centers around the general omics process flow, with concepts that denote the individual steps, such as sample processing, assay, and data processing. Genomics-specific specializations are provided, such as library preparation, sequencing assay, and sequencing analysis. The schema also facilitates in capturing other important omics metadata, such as information about the sequencing instrument, standard operating procedure, and quality control metrics. The extension aligns with existing semantic data models and reuses common biomedical vocabularies, such as EDAM, OBI and FAIR genomes, as value sets, thereby facilitating semantic interoperability. It will be used to FAIRify data that is produced within the Swiss network and to facilitate sharing this data as one knowledge graph for reuse among its participants.

Background: Chronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression. Materials and Methods: The study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2020 and September 2023. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved byscientific and ethical review committees of all participating centers. Sanger sequencing was employed to detect ANKRD36mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36.Results: During our study, 17% of CML patients progressed to advanced phases AP-CML n= 11 (8.9%) and BC-CML n=10(8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c.1183_1184 delGC and c.1187_1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML. Conclusions: The study confirms ANKRD36 as a novelgenomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

Chimeric antigen receptor and T-cell receptor (CAR-T/TCR) cellular immunotherapies have shown remarkable success in the treatment of some refractory B-cell malignancies, with potential to provide durable clinical response for other types of cancer. In this paper, we look at all available FDA CAR-T/TCR clinical trials for the treatment of cancer, and analyze them with respect to different disease tissues, targeted antigens, products, and originator locations. We found that 627 of 1,007 registered are currently active and of those 273 (44%) originated in China and 280 (45%) in the US. Our analysis suggests that the rapid increase in the number of clinical trials is driven by the development of different CAR-T products that use a similar therapeutic approach. We coin the term bioparallels to describe such products. Our results suggest that one feature of the CAR-T/TCR industry may be a robust response to success and failure of competitor products.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798, had shown the highest level of evidence about their association with FPs response. The EMA and FDA-approved drug labels for FPs, recommend genotyping these variants before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still find patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the association with the response to FPs of DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595; as explanatory candidates of the interindividual differences for the FP-related toxicities. We also studied the impact of DPYD*2A, *13, *HapB3, and rs67376798 genotype for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found that FP dose lowering based on DPYD genotype does not affect the treatment efficacy. Also, the DPYD*4 (defined by rs1801158) allele was associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R.= 5.66; 95% C.I.= 1.35 – 23.67; p= 0.014) and multivariate analyses (O.R.= 5.73; 95% C.I.= 1.41 – 28.77; p= 0.019). This makes it a candidate variant for implementation in clinical practice.

Background/Objectives:The first attempts of posterior lumbar interbody fusion can be traced back to the 1940s, where their performance was marked by animosity due to high rates of failure. Nowadays, the use of interbody fusion involves a much more complicated consideration of factors such as global alignment, disc height, fusion rates, and operative risk, all combined at once.Our study aims to examine all these effects using Flarehawk 9 as a means of interbody fusion.Materials and methods: A total of 58 patients underwent open posterior lumbar surgery using Flarehawk 9 between September 2021 and February 2023 with a mean follow up of 1 year.The mean age was 59.8 years old ( range between 33 and 79 years old), 36 of them are males while 22 of them are females. The diagnostic groups included spinal canal stenosis (n=40), failed back surgery syndrome-revision surgery (n=5),spondylolisthesis with slip percentage 25% (n=4),recurrent herniated disc (n=7) and adjacent segment disease (n=2). Results: The majority of patients demonstrated remarkable improvement based on ODI scores.The rate of union varied based on the fused levels and whether the patients had previous surgery or not.The amount of lordosis postoperatively is increased by 2±0.4 degrees.Conclusions: Even though anterior approaches become more and more popular and advanced nowadays, posterior fusion with interbody cage still remains a safe and effective method to treat various spine surgical pathologies with optimal results.

A cross-sectional study was carried out to determine the prevalence of subclinical mastitis (SCM) among medium to large scale household dairy farms in southwestern district, Jhenaidah, Bangladesh during July to December 2019. A total of 78 (n=100) lactating cows from household dairy farms (N=32) having three or more dairy cows were selected randomly as sampled populations. Milk samples were screened for SCM by using Surf Field Mastitis Test (SFMT). The prevalence of SCM varied among farm level [71.9% (95% CI: 53.3-86.3)], individual animal level [67.9% (95% CI: 56.4-86.3)] and quarter level [29.5% (95% CI: 24.5-34.9)]. Descriptive statistics represented the farmers and farm demography, characteristics of the sampled population, and overall management feature. Random Effect Logistic Regression identified, Body Condition Score (BCS) [OR=3.8 and 2.9, at cows level and quarter level respectively (BCS-2 vs. BCS-≥3)], and breed [OR=5.1 and 2.9, at cows level and quarter level respectively (HF× Sahiwal vs. HF × Local)] as potential risk factors. This study shows that SCM is highly prevalent in the study area, which is a major threat to the dairy industry's production performance. Regular screening by SFMT, proper hygiene, improve the management system, and farmer’s awareness is required to control the disease.

Background: In response to inflammation, the absorption of nutritional iron is restricted. Multiple inflammation-related signaling pathways can lead to ferroptosis, an iron-dependent mechanism of programmed cell death. Since the pathophysiological significance of the presence and uptake of iron in chronic inflammation is still unknown, we tested the effect of a low iron diet on the clinical course of arthritis in the mouse model of collagen-induced arthritis (CIA). Methods: Six- to eight-week-old male DBA/1 mice were fed either a normal or a low iron diet starting three weeks before arthritis induction. From day four after the collagen-booster made on day 25, the development of arthritis was regularly monitored until the end of the experiment (day 34), using a standard clinical arthritis score. The complete blood count was determined as well as Fe2+, Fe3+, oxidized and reduced glutathione (GSH and GSSG) and malondialdehyde (MDA) in whole paw tissue by ELISA. Quantitative PCR was performed from whole paw tissue for glutathione peroxidase 4 and other key regulator genes of iron metabolism and ferroptosis. We used nonparametric tests to com-pare markers of iron metabolism and ferroptosis as well as nonlinear regression models for longitu-dinal data for signs of arthritis. Results: Mice fed a low iron diet showed a significantly less severe course of arthritis compared to mice fed a normal iron diet (p

The FDA has concluded that a biosimilar candidate capable of demonstrating pharmacodynamic biomarkers in a healthy subject need not be tested for clinical efficacy in patients, regardless of if the biomarker correlates with clinical response. Since monoclonal antibodies (mAbs) do not trig-ger pharmacodynamic response, they can be substituted with robust functional disqualifying them for this waiver that can be overcome by allowing comparison of functional properties that eventually result in clinical response. This suggestion is based on the FDA's preference for more sensitive testing methods. However, clinical efficacy testing in patients is the least sensitive method, as confirmed by statistical modeling, a fact that regulatory agencies need to admit. In this paper, I present a logical and rational argument to establish the biosimilarity of products that do not have pharmacodynamic biomarkers based on their orthogonally proven functional bio-similarity. This understanding will significantly lower the development cost of biosimilars, a goal that the FDA outlined in all its guidance. Keywords: biosimilarity 1; biosimilars 2; pharmacodynamic biomarkers 3; monoclonal antibodies 4; FDA 5; clinical efficacy testing in healthy subjects 6; clinical efficacy testing in patients 7; functional assays 8; receptor binding 9.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

Clopidogrel is one of the most prescribed antiplatelet drugs for cardiovascular diseases prevention. Clopidogrel is a prodrug metabolised by CYP2C19 in active metabolites with anti-aggregant effect. Pharmacogenetic variants such as CYP2C19*2 variant can alter the anti-aggregant effect of clopidogrel leading to a higher risk of cardiovascular disease relapse. The aim of this study was to evaluate the prescription characteristics of CYP2C19 pharmacogenetics in patients on clopidogrel treatment, based on a specific query in a clinical data warehouse. We evaluated the demographics of patients, prescribers, medical indications, CYP2C19 pharmacogenetic tests and therapeutic changes. Neurologists were the main prescribers of CYP2C19 pharmacogenetic tests associated with clopidogrel treatment in a context of suspicion of stroke relapse. Pharmacogenetic tests were mainly prescribed a posteriori to clopidogrel prescription. Clopidogrel pharmacogenetic resistance was associated with the prescription of lysine acetylsalicylate in substitution of clopidogrel. Clear clinical practice guidelines are needed to position CYP2C19 pharmacogenetic testing for patients on clopidogrel treatment.

Over a year into the COVID-19 pandemic, there is growing evidence that SARS-CoV-2 infections among dogs are more common than previously thought. In this study, the prevalence of SARS-CoV-2 antibodies was investigated in two dog population. The first group was comprised of 1069 dogs admitted to the Veterinary Teaching Hospital for any given reason. The second group included dogs that shared households with confirmed COVID-19 cases in humans. This study group numbered 78 dogs. In COVID-19 infected households, 43.9% tested ELISA positive, and neutralisation antibodies were detected in 25.64% of dogs. Those data are comparable with the secondary attack rate in the human population. With 14.69% of dogs in the general population testing ELISA positive, there was a surge of SARS-CoV-2 infections within the dog population amid the second wave of the pandemic. Noticeably seroprevalence of SARS-CoV-2 in the dog and the human population did not differ at the end of the study period. Male sex, breed and age were identified as significant risk factors. This study gives strong evidence that while acute dog infections are mostly asymptomatic, they can pose a significant risk to dog health. Seropositive dogs had a 1.97 times greater risk for developing central nervous symptoms.

Because the including of human anatomy forms the foundation for clinical medicine, it has contributed a pivotal role in medical education for many centuries. Thus with advancements in the science of modern, current day medicine, its continued place in the medical school curriculum deserves careful attention. In an attempt to provide guidance to decision-makers involved in clinical anatomy curriculum development at the medical school level, the Educational Affairs Committee of the American Association of Clinical Anatomists (AACA) developed this document, which defines the contours of a gross anatomy curriculum leading to the M.D. or D.O. degree. The main body of the document sets forth the anatomical concepts as well as the subject matter a student should master prior to graduation from medical school. Gross anatomy dissection is still a crucial topic in graduate and medical school. The nature and content of gross anatomy, which was historically regarded as a core course in the first year of medical education in MBBS, MD, DO, and some PhD and Graduate curricula as well as in other disciplines of selective graduate education and non-allopathic medical programs, have been significantly impacted by emerging challenges in the pedagogy of delivering medical education in the past ten years. A seemingly ever-increasing emphasis on additional modules in molecular biology, emerging pharmacotherapeutics and pathophysiology content have resulted in a condensation and apparent erosion of previously allotted classroom and laboratory hours in the gross anatomy curriculum. In addition, an imposition of financial constraints and a decreasing availability of sufficient cadaver donations to support gross anatomy dissection labs has also occurred in some locations. An innovative clinically focused cadaveric anatomy program is described which has improved the delivery and content retention of medical and graduate students and has become one of the most sought-after modules in the revised clinically oriented curriculum and has been deemed highly relevant to current medical education and graduate studies.

Dietzia natronolimnaea C79793-74 has emerged as a potential probiotic strain with implications for managing Crohn's disease. This study evaluates the safety profile of D. natronolimnaea C79793-74 as a probiotic sup-plement. Genotypic characterization involved a 16S rRNA gene and genomic sequencing and genome an-notation. The safety assessment included interrogation of the assembled genome for antibiotic resistance genes and virulence factors, utilizing the CARD and VFDB databases. Notably, the analysis revealed an ab-sence of antibiotic resistance or virulence factors in Dietzia natronolimnaea C79793-74. The safety and tol-erability of D. natronolimnaea C79793-74 were further investigated in an 8-week double-blind, place-bo-controlled clinical trial involving healthy adult participants. A daily dose of 5 x 109 CFU of the probiotic strain was administered. This clinical trial represents the first assessment of the safety of D. natronolimnaea C79793-74 in human subjects. Results demonstrated that participants in both the Dietzia and Placebo groups maintained clinical and hematologic markers within the normal range throughout the study. More-over, the probiotic strain was well-tolerated, with nearly all participants experiencing no severe or medium adverse events. Collectively, the comprehensive data obtained in this study support the inference that Dietzia natronolimnaea C79793-74 is safe and well-tolerated as a nutritional supplement for human con-sumption

Implementing the methodology of clinical simulation in the nursing degree course is a necessity in the European framework of higher education to acquire competences. The objectives of this research were to evaluate the strategies and techniques used during the simulations, identify the contents learned, and determine which of them are transferred to the nursing practice. We performed an observational, descriptive, and cross-sectional study from the nursing students’ perspective during the 2020-21-year course. On the one hand, our results show that the DASH scale helped us to obtain an internal validity of the simulations obtaining a mean score of 6.61 out of 7. On the other hand, the Ad Hoc scale, based on the competences were acquired in the simulations were transferred to the care practices. In conclusion, it is possible to improve care practices by integrating knowledge through clinical simulations.

The widely spread CoronaVirus Disease (COVID)- 19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.

Preoperative assessment is crucial in surgical care, traditionally relying on physical examinations and paper-based questionnaires. The emergence of digital tools like Pathpoint® ePOA represents a significant advancement, aiming to enhance the efficiency, accuracy, and standardisation of preoperative evaluations. Pathpoint® ePOA is a cloud-based platform designed to integrate seamlessly with Electronic Health Records (EHRs), providing a comprehensive, data-driven approach to preoperative assessments. It supports improved risk stratification, optimised resource allocation, and enhanced patient engagement through features such as customisable templates and real-time data integration.Current research highlights that digital preoperative tools like ePOA offer notable advantages, including increased clinical capacity, better complexity stratification, and improved patient follow-up. Despite these benefits, gaps remain in comparative studies, detailed clinical outcomes, and patient engagement strategies, indicating areas for further exploration. Pathpoint® ePOA adheres to rigorous safety standards and risk management protocols, ensuring reliability and data security while contributing to improved surgical outcomes. The benefit-risk ratio for ePOA is favourable, underscoring its potential to advance preoperative care by optimising clinical workflows and enhancing patient safety.

Managing blood cholesterol levels is important for the treatment and prevention of diabetes, cardiovascular disease, and obesity. An easy-to-use, portable cholesterol blood test will accelerate more frequent testing by patients and at-risk populations. We aim to evaluate the performance of smartphone-based point-of-care cholesterol blood tests as compared to that of hospital-grade laboratory tests. We used smartphone systems that are already familiar to many people. Because smartphone systems can be carried around everywhere, blood can be measured easily and frequently. We compared the results of cholesterol tests with those of existing clinical diagnostic laboratory methods. We found that smartphone-based point-of-care lipid blood tests are as accurate as hospital-grade laboratory tests (N=116, R>0.97, P<0.001 for all 3 cholesterol blood tests: total cholesterol, high density lipoprotein, and triglyceride). Our system will be useful for those who need to manage blood cholesterol levels to motivate them to track and control their behavior.

Background: Caring for individuals with mental disorders poses significant challenges for caregivers, often leading to compromised quality of life and mental health issues such as stress, anxiety, and depression. This study aims to assess the extent of these challenges among caregivers in Greece, identifying which demographic factors influence their well-being. Method: A total of 157 caregivers were surveyed using the SF-12 Health Survey for quality of life assessment and the DASS-21 questionnaire for evaluating stress, anxiety, and depression symptoms. T-tests, Kruskal-Wallis tests, Pearson correlation coefficients, and regression analyses were applied to understand the associations between demographics, quality of life, and mental health outcomes. Results: The study found that caregivers, especially women and younger individuals, faced high levels of mental health challenges. Marital status, educational level, and employment status also significantly influenced caregivers' well-being. Depression was the most significant factor negatively correlating with the mental component of quality of life. The magnitude of burden experienced by caregivers highlighted the urgency for targeted social and financial support, as well as strategic treatment programs that consider caregiver well-being. Conclusions: Caregivers of individuals with mental disorders endure significant stress, anxiety, and depression, influencing their quality of life. Demographic factors such as age, gender, marital status, education, and employment status have notable impacts. Findings emphasize the need for society-wide recognition of caregivers' roles and the creation of comprehensive support and intervention programs to alleviate their burden, particularly in the context of the COVID-19 pandemic.

Bovine mastitis is the most impacting disease of dairy industry, and it is characterized by a complexity of causal agents, which have revealed a geographical variation among regions and countries. The mastitis-related pathogens have been traditionally classified as contagious or environmental, based on habits of the microorganisms and transmission routes. In addition, the severity of mammary infections has been associated with the virulence of the pathogens, and immune and nutritional status of the hosts. Considering this scenario, we investigated the etiological nature, clinical severity scores, and days in milk (DIM) data in 4,273 clinical cases of bovine mastitis among ten large-dairy farms located in the Southeast region of Brazil. Streptococcus dysgalactiae (283/4,273=6.6%), Escherichia coli (190/4,273=4.4%), Prototheca spp. (112/4,273=2.6%), and Streptococcus uberis (95/4,273=2.2%) were the predominant pathogens isolated, all from the environmental origin. Among 4,273 clinical cases, clinical gravity score was available in 43.8% (1,871/4,273) animals. From these, 69.8% (1,306/1,871), 27.3% (510/1,871) and 2.9% (55/1,871) were scored as mild, moderate, and severe, respectively. Most of isolation of pathogens were observed in the first 100 days in milk, and their clinical severity scored as mild (3,612/4,273=84.5%). Our results contribute to the etiological identification, clinical severity scoring, and milking aspects of bovine clinical mastitis in dairy farms with a history of clinical mammary infections.

About half of the world's population is at risk of dengue infection. Epidemics of dengue fever caused an increased risk of morbidity and mortality in recent years, which led to the exploration of vaccines as a preventive measure. This systematic review and meta-analysis aimed to evaluate the efficacy, immune response, and safety of dengue vaccines in children by analyzing clinical trials. The review followed standard procedures for data extraction using PRISMA guidelines, and searching multiple databases including PubMed, CINAHL, Medline, Health Source, Science Direct, and Academic Search Premiere. Eligible studies involved children (0-17 years). Cochrane Collaboration criteria were used for quality assessment, with thematic data synthesis and meta-analysis. Among 38 selected studies, dengue vaccines showed varying efficacy against all four serotypes. CYD-TDV (Dengvaxia®), and Tekade (TAK-003) vaccines demonstrated strong protection against severe dengue, but their long-term efficacy varied. Vaccines triggered satisfactory immune responses, notably in those previously exposed to dengue. Safety profiles were mostly favorable, noting mild adverse events post-vaccination. Meta-analysis supported vaccine efficacy and immune response, but safety concerns warrant further exploration. In conclusion, dengue vaccines demonstrated promising efficacy and immune response, particularly against severe manifestations.

Background. Until now, cost of allergy treatment in insured public health care system and non-insured self-financing private health care system in Indonesia has not been well documented and published, as well as the cost of allergy treatment with subcutaneous immunotherapy. Objective. To evaluate the clinical and cost benefits of allergic rhinitis treatment in children with subcutaneous immunotherapy in non-insured self-financing private health care system. Methods. A retrospective cohort study conducted from 2015 until 2020, compared clinical improvement and health care costs over 18 months in newly diagnosed AR children who received SCIT versus matched AR control subjects who did not receive SCIT, with each group consisting of 1,098 subjects Results. Decrease of sp-HDM-IgE level (kU/ml) from 20.5 + 8.75 kU/ml to 12.1 + 3.07 kU/ml had been observed in the SCIT group. To reduce the symptom score of allergic rhinitis by 1.0 with SCIT it costs IDR 21,753,062.7 per child, for non SCIT it costs IDR 104,147,878.0 per child. Meanwhile, to reduce the medication score (MS) by 1.0 with SCIT it costs Rp. 17,024,138.8 while with non SCIT it costs Rp. 104,147,878.0. Meanwhile, to lower combination symptoms and medication score (CSMS) by 1.0, with SCIT it costs IDR 9,550,126.6, while with non SCIT it costs IDR 52,073,938.9. Conclusion. In conclusion, this first Indonesia-based study demonstrates substantial health care cost savings associated with SCIT for children with AR in an uninsured private health care system and provides strong evidence for the clinical benefits and cost-savings benefits of AR treatment in children.

Coronavirus Disease 2019 (COVID-19), caused by a novel coronavirus named Severe Acute Respiratory Syndrome - Coronavirus-2 (SARS-CoV-2), emerged in early December 2019 in China and attained a pandemic situation worldwide by its rapid spread to nearly 167 countries with 287.239 confirmed cases and 11.921 human deaths with a case fatality rate (CFR) of around 4 per cent. Bats were considered as the reservoir host, and the search of a probable intermediate host is still going on. Animals have anticipated culprit of SARS-CoV-2 as of now. The disease is mainly manifested by pneumonia and related respiratory signs and symptoms, but the involvement of the gastrointestinal system and nervous system is also suggested. The severe form of the disease associated with death is mainly reported in older and immune-compromised patients with pre-existing disease history. Death in severe cases is attributed to respiratory failure associated with hyperinflammation. Cytokine storm syndrome associated with rampant inflammation in response to SARS-CoV-2 infection is considered as the leading killer of COVID-19 patients. COVID-19 patients were reported with higher levels of many pro-inflammatory cytokines and chemokines like IFN-g, IL-1b, IP-10, and MCP-1. Furthermore, severe cases of COVID-19 revealed higher levels of TNF-α, G-CSF, and MIP-1A. Blood profile of the COVID-19 patients exhibits lymphopenia, leucopenia, thrombocytopenia and RNAaemia along with increased levels of aspartate aminotransferase. SARS-CoV-2 infection in pregnant women does not lead to fetus mortalities unlike other zoonotic coronaviruses like SARS-CoV and MERS-CoV, with no evidence of intrauterine transmission to neonates. Rapid and confirmatory diagnostics have been developed, and high efforts are being made to develop effective vaccines and therapeutics. In the absence of any virus-specific therapeutic, internationally health care authorities are recommending adoption of effective prevention and control measures to counter and contain this pandemic virus. This paper is an overview of this virus and the disease with a particular focus on SARS-COV-2 / COVID-19 clinical pathology, pathogenesis and immunopathology along with a few recent research developments.

Patients with non-union fractures spend extended periods in the hospital following poor healing. Patients have to make several follow-up visits for medical and rehabilitation purposes. However, the clinical pathways and quality of life of these patients are unknown. This prospective study aimed to identify the clinical pathways (CPs) of 22 patients with lower limb non-union fractures whilst determining their quality of life. Data were collected from hospital records on admission through discharge, utilising a CP questionnaire. We used the same questionnaire to track patients' follow-up frequency, involvement in activities of daily living, and outcomes at six months. We used the short form-36 questionnaire to assess patients’ initial quality of life. The Kruskal-Wallis test compared the quality of life domains across different fracture sites. We examined CPs using medians and inter-quantile ranges. During the six-month follow-up period, 12 patients with lower limb non-union fractures were readmitted. All of the patients had impairments, limited activity, and participation restrictions. Lower limb fractures can have a substantial impact on emotional and physical health, and lower limb non-union fractures may have an even greater effect on the emotional and physical health of patients, necessitating a more holistic approach to patient care.

We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP) and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist-hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted to statistical analysis (α=0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD and CAL, which were statistically significant at 90 and 180 days (p&lt;0.0001). Importantly, NSPT significantly reduced the blood level of CRP (p&lt;0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.

Validation and verification are the critical requirements in the knowledge acquisition method for the clinical decision support system (CDSS). After acquiring the medical knowledge from diverse sources, the rigorous validation and formal verification process are required before creating the final knowledge model. Previously, we have proposed a hybrid knowledge acquisition method for acquiring medical knowledge from clinical practice guidelines (CPGs) and patient data in the Smart CDSS for treatment of oral cavity cancer. The final knowledge model was created by combining knowledge models obtained from CPGs and patient data after passing through a rigorous validation process. However, detailed analysis shows that due to lack of formal verification process, it involves various inconsistencies in knowledge relevant to the formalism of knowledge, conformance to CPGs, quality of knowledge, and complexities of knowledge acquisition artifacts. Therefore, it is required to enhance a hybrid knowledge acquisition method that thwarts the inconsistencies using formal verification. This paper presents the verification process using the Z formal method and its outcome as an enhanced acquisition method – known as the refined knowledge acquisition (ReKA) method. The ReKA method adopted verification method and explored the mechanism of theorem proving using the Z notation. It enables to identify inconsistencies in the validation process used for hybrid knowledge acquisition. Additionally, it refines the hybrid knowledge acquisition method by discovering the missing steps in the current validation process at the acquisition stage. Consequently, ReKA adds a set of nine additional criteria to be used to have a final valid refined clinical knowledge model. The criteria ensure the validity of final knowledge model concerning formalism of knowledge, conformance to GPGs, quality of the knowledge, usage of stringent conditions and treatment plans, and inconsistencies possibly resulting from the complexities. Evaluation, using four medical knowledge acquisition scenarios, shows that newly added knowledge in CDSS due to the addition of criteria by ReKA method always produces a valid knowledge model. The final knowledge model was also evaluated with 1229 oral cavity patient cases, which outperformed with an accuracy of 72.57\% compared to a similar approach with an accuracy of 69.7\%. Furthermore, ReKA method identified a set of decision paths (about 47.8%) in the existing approach, which results in a final knowledge model with low quality, non-conformed from standard CPGs. In conclusion, ReKA is formally proved method which always yields valid knowledge model having high quality, supporting local practices, and influenced from standard guidelines.

Computed tomography (CT) is a widely employed imaging modality with diverse clinical applications in pediatric and adult populations, offering numerous advantages. Despite several alternatives to imaging modalities with ionising radiation, CT scans have demonstrated persistent global popularity, contributing to a substantial amount of effective radiation doses for patients. This exposure results in hazards, including stochastic effects that amplify the radiation-induced cancer risk proportionally to the radiation dose received. CT-related radiation comprises a substantial portion of cumulative effective doses within diagnostic radiology, specifically impacting younger patient cohorts undergoing repeated investigations for chronic diseases over time. Scientific literature over recent decades has explored various methods to mitigate radiation doses during medical imaging. One notable strategy involves implementing low-dose and ultralow-dose CT protocols, maintaining diagnostic efficacy in acute and non-acute medical and surgical conditions. Utilising innovative image reconstruction algorithms, such as iterative reconstruction and emerging deep-learning algorithms based on artificial intelligence, plays a pivotal role in achieving an approximately 80% reduction in patient radiation compared to standard doses. This review article discusses the significance of low-dose protocols across a spectrum of acute and chronic medical conditions affecting different body systems.

This study aimed to explore how Indonesian clinical psychologists (CPs) address aspects of spirituality and religion (SR), particularly their attitudes towards and experience of it, on the mental health context. Semi-structured interviews were conducted with 43 CPs in public health centres in Yogyakarta Province, Indonesia. Data were anyalsed using deductive thematic analysis and they generated ten sub-themes which were merged into three central themes. The first theme was experiences related to SR, particularly in Indonesian sociocultural context. The second theme concentrated on participants’ clinical experience related to SR integration into clinical practice. The last theme highlighted the effort made by participants to create holistic mental health services. The originality of this study was represented by the interview quote in the title, “Doing my profession is also part of worship”. It was found that SR is part of culture and belief among Indonesian people, including CPs and mental health treatment clients. In summary, participants genuinely acknowledged that they were not able to completely detach SR from their professional practice. However, participants also pointed out that they were different with spiritual-religious healers (SRHs) and favourably welcomed future collaboration with credible SRHs. This positive attitude embodied a holistic care approach that recognises the diverse biopsycho-social-spiritual needs of clients. Therefore, professional organisations and psychology faculties should establish regulations and education of SR in psychology curricula and conventional psychotherapy to achieve this holistic mental health services in Indonesia.

Since the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting in different studies, we performed this meta-analysis. A systematic search of published articles was performed in PubMed and EMBASE from January-May 5, 2020. Studies that reported the clinical outcomes of patients with COVID-19, stratified by the class of concomitant antihypertensive drug therapy, were included. The Mantel-Haenszel random effects model was used to estimate pooled odds ratio (OR). A total of 6,997 hypertensive patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR=0.84, 95% CI: [0.73, 0.96]; P=0.017) compared with those receiving non-RAAS inhibitor antihypertensives. Patients taking angiotensin-I-converting enzyme inhibitors (ACEIs) were less likely to experience poor clinical outcomes (OR=0.73, 95% CI: [0.58-0.92]; P=0.01) compared with those receiving angiotensin-II receptor blockers (ARBs). Compared to all other antihypertensives, ACEIs decreases the risk poor COVID-19 outcomes (OR=0.77, 95% CI: [0.63-0.93]) while ARBs did not (OR=1.13, 95% CI: [0.95-1.35]). The risk of poor patient outcomes from COVID-19 was lower in patients who received RAAS inhibitors compared with those who took non-RAAS inhibitors. Unlike ARBs, ACEIs might help in decreasing the severity and mortality of COVID-19.

Wearable antennas are increasingly vital in modern healthcare, facilitating continuous monitoring and communication for medical purposes. These antennas are integrated into wearable devices, allowing for the transmission and reception of vital health data, such as heart rate, body temperature, and blood pressure, to medical professionals or monitoring systems in real time. This instantaneous data transmission enables timely interventions, thus improving the quality of healthcare services. This review aims to comprehensively synthesize recent research from reputable databases, focusing on the functionality and effectiveness of wearable antennas in medical applications. The primary objectives of each study were categorized, including antenna design and integration, the performance of medical wearable antenna technology, safety considerations in wearable antenna biomedicine, and the use of antennas in clinical applications and their impact. This synthesis provides valuable insights for researchers and practitioners aiming to develop and deploy wearable antennas in medical settings, ultimately enhancing healthcare delivery and patient outcomes.

Fractional flow reserve (FFR) is regarded as the gold standard for assessing the functional significance of coronary artery lesions, yet it remains underutilized in clinical practice. Our objective was to investigate whether FFR results have the potential to alter treatment decisions for coronary lesions compared to visual assessments of angiographic images made by three operators at a high-volume interventional center. In this retrospective study, we aimed to reassess the angiographic images of 63 patients presenting with chronic coronary syndrome (n=39, 61.9%) and acute coronary syndrome (n=24, 38.1%) who underwent FFR. Three experienced interventional cardiologists (with >300 PCI procedures per year) reevaluated, blinded to FFR results, 105 ambiguous lesions in 63 patients to determine angiographic significance and treatment strategy. The observers reached a concordant agreement (≥2 operators made the same decision) to perform PCI in 60 (57.1%) of the lesions based on angiographic evaluation. Interestingly, 9 (15%) of these lesions were functionally non-significant (FFR &gt;0.80). The observers agreed to defer PCI in 45 (42.9%) of the lesions; however, 4 (8.9%) of these were functionally significant (FFR ≤0.80) and required PCI. Thus, inter-observer concordance in visual-guided therapeutic decision-making is variable and not always confirmed by the functional significance of coronary lesions.

: Background: Parkinson’s disease (PD) is a chronic, progressive illness with a profound impact on health-related quality of life, and it is crucial to know what factors influence quality of life throughout the course of the disease. This study aimed to evaluate PD patients’ motor and non-motor symptoms to compare symptom severity between PD clinical phenotypes and to assess the impact of disease symptoms on quality of life in a cohort of Latvian patients. Methods: We evaluated 43 patients with Parkinson’s disease. Fourteen patients had tremor-dominant (TD) PD, twenty-five patients had postural instability/gait difficulty (PIGD), and four patients had a mixed phenotype. Results: The patients’ mean age was 65.21 years, and the disease’s mean duration was 7 years. The most common non-motor symptoms were fatigue (95.3%), sleep disturbance (83.7%), daytime sleepiness (83.7%), and pain and other sensations (81.4%). PIGD patients had a higher prevalence of depressed mood, daytime sleepiness, constipation, light headedness on standing, cognitive impairment, and severe gastrointestinal and urinary disturbances (as assessed using the SCOPA-AUT domains) compared with TD patients. A high prevalence of fatigue was assessed in both disease subtypes. Health-related quality of life significantly statistically correlated with MDS-UPDRS parts III and IV (r = 0.704), the Hoehn and Yahr scale (r = 0.723), as well as the SCOPA-AUT scale’s gastrointestinal (r = 0.639), cardiovascular (r = 0.586), thermoregulatory (r = 0.566) and pupillomotor domains (r = 0.597). Conclusion: The severity of motor symptoms, as well as non-motor symptoms, such as fatigue, apathy, sleep problems and daytime sleepiness, pain, and disturbances in gastrointestinal and cardiovascular function, negatively affect PD patients’ health-related quality of life. Thermoregulatory and pupillomotor symptoms also significantly affect PD patients’ well-being.

The overall objective of this mixed-method digital-based observational study was to determine the mental health impact among CTU staff working during the COVID-19 pandemic. The Qualtrics Core XM platform was used to deploy the questionnaire where a quantitative analysis was conducted. The qualitative part of the study used the Microsoft Teams digital application to complete the interviews. Various validated mental health assessments were administered: Vancouver Index of Acculturation (VIA), Hospital Anxiety and Depression Scale (HADS), Insomnia Severity Index (ISI), Pandemic Stress Index (PSI), Burnout Assessment Tool-12 (BAT-12), General Self Efficacy Scale (GSE) and The Everyday Discrimination Scale (EDS). A total of 485 participants took part, of which 73.4% were female and 70.1% of the sample were white British. A high prevalence of anxiety, exhaustion and depression were identified across all participants. A significant mental health impact was identified among the CTU workforce where wellbeing was compromised during the course of the COVID-19 pandemic.

Objective: The purpose of this study was to determine if Porphyra tenera extract (PTE) has immune-enhancing effects and is safe in healthy adults. Methods: Subjects (3x10³ ≤ peripheral blood leukocyte levels < 8x10³ cells/μl) who met the inclusion criteria were recruited for this study. Enrolled subjects (n=120) were randomly assigned to either the PTE group (n=60) who were given 2.5 g/day of PTE (as Porphyra tenera extract) in capsule form or the placebo group (n=60) who were given crystal cellulose capsules with the identical appearance, weight, and flavor as the PTE capsules for 8 weeks. Outcomes were assessed by measuring natural killer cell (NK-cell) activity, cytokines, and upper respiratory infection (URI), and safety parameters were assessed at baseline and 8 weeks. Results: Compared to baseline, NK cell activity (%) increased for all effector cell to target cell ratios in the PTE group after 8 weeks, but there were no changes in the placebo group (p<0.1). Subgroup analysis of 101 subjects without an URI revealed that NK-cell activity in the PTE group tended to be increased for all E:T ratios (E:T=12.5:1 p=0.068; E:T=25:1 p=0.036; E:T=50:1 p=0.081) compared to the placebo group. There was a significant difference between these two groups for the E:T=25:1 ratio, which increased from 20.3±12.0% at baseline to 23.2±12.4% after 8 weeks in the PTE group (p=0.036). There was no significant difference in levels of cytokines between these two groups. Conclusions: PTE supplementation appears to enhance immune function by improving NK-cell activity without adverse effects in healthy adults.

Efficient triaging and referral assessment are critical in ensuring prompt medical intervention in the Community Health Care (CHC) system. However, the existing triaging systems in many Community Health Services are an intensive, time-consuming process and often lack accuracy, particularly for various symptoms that might represent heart failure or other health-threatening conditions. There is a noticeable limit of research papers describing AI technologies for triaging patients. This paper proposes a novel quantitative data-driven approach using machine learning (ML) modelling to improve the community clinical triaging process. Furthermore, this study aims to employ the feature selection process and machine learning power to reduce the triaging process’s waiting time and increase accuracy in clinical decision-making. The model was trained on medical records of “Heart Failure” patients’ dataset, which included demographics, past medical history, vital signs, medications, and clinical symptoms. A comparative study was conducted using the list of machine learning algorithms where XGBoost demonstrated the best performance among other ML models. The triage levels of 2,35,982 patients achieved an accuracy of 99.94%, precision of 0.9986, recall of 0.9958, and f1-score of 0.9972 within 0.059 seconds. The proposed diagnostic model can be implemented for the CHC decision system and be developed further for other medical conditions.

Background Frequent presenters (FPs) define a group of individual who visit hospital emergency depart-ment (ED) frequently for urgent care. Many among the group present with main diagnosis of mental health conditions. This group of individual tend to use ED resources disproportionally and significantly affect overall healthcare outcome. No previous reviews have examined the profiles of FPs with mental health conditions. Aims This study aims to identify the key socio-demographic and clinical characteristics of patients who frequently present to ED with mental health primary diagnosis by performing systemic review from existing literature. Method PRISMA guideline was used. PubMed, PsycINFO, Scopus and Web of Science (WOS) were searched in May 2023. A manual search on reference list of included articles were conducted at same time. Covidence was used to perform extraction and screening, completed by two authors independently. Inclusion and exclusion criteria were defined. Results The abstracts of 3341 non-duplicate articles were screened with 40 full texts assessed for eligi-bility. 20 studies were included from 2004-2022 conducted in 6 countries with total patient number of 25688 (52% male, 48% female, mean age 40.7 years old). 27% were unemployed, 20% married, 41% homeless, and 17% had tertiary or above education. 44% had history of substance abuse or alcohol dependence. Top 3 diagnosis are found to be anxiety disorders (44%), depressive disorders (39%) and schizophrenia spectrum and other psychotic disorders (33%). Conclusion On average, FPs are middle aged and equally prevalent in both gender. Current data lacks rep-resentation for gender diverse group. They are significantly associated with high rate of unem-ployment, homelessness, lower than average education level, and being single. Anxiety disor-der, depressive disorder, and schizophrenia spectrum disorders are the most common clinical diagnosis associated with the group.

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We have previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its’ potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicate its’ potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, especially in pediatric malignant gliomas. We also summarize BMP4 delivery strategies, with a focus on biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

Background. It is unclear whether the use of clinical prediction rules is sufficient to rule out infective endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) without an echocardiogram evaluation, either transthoracic (TTE) and/or transesophageal (TEE). Our primary purpose was to test the usefulness of PREDICT, POSITIVE and VIRSTA scores to rule out IE without echocardiography. Our secondary purpose was to evaluate whether not performing an echocardiogram evaluation is associated with higher mortality. Methods. We conducted a unicentric retrospective cohort including all patients with a first SAB episode from January 2015 to December 2020. IE was defined according to modified Duke criteria. We predefined threshold cut-off points to consider that IE was ruled out by means of the mentioned scores. To assess 30-day mortality, we used a multivariable regression model considering performing an echocardiogram as covariate. Results. Out of 404 patients, IE was diagnosed in 50 (12.4%). Prevalence of IE within patients with negative PREDICT, POSITIVE and VIRSTA scores was: 3.6% (95% CI 0.1-6.9%), 4.9% (95% CI 2.2-7.7%), and 2.2% (95% CI 0.2-4.3%), respectively. Patients with negative VIRSTA and negative TTE had an IE prevalence of 0.9% (95% CI 0-2.8%). Performing an echocardiogram was independently associated with lower 30-day mortality (OR 0.24 95%CI 0.10-0.54, p=0.001). Conclusion. PREDICT and POSITIVE scores were not sufficient to rule out IE without TEE. In patients with negative VIRSTA score, it was doubtful if IE could be discarded with a negative TTE. Not performing an echocardiogram was associated with worse outcomes, which might be related to presence of occult IE. Further studies are needed to assess the usefulness of clinical prediction rules in avoiding echocardiographic evaluation in SAB patients.

(1) Background: the NGS based mutational study of hereditary cancer genes is crucial to design tailored prevention strategies in subjects with different hereditary cancer risk. The ease of amplicon-based NGS library construction protocols contrasts with the greater uniformity of enrichment provided by capture-based protocols and so with greater chances for detecting larger genomic rearrangements and copy-number variations. Capture-based protocols, however, are characterized by a higher level of complexity of sample handling, extremely susceptible to human bias. Robotics platforms may definitely help dealing with these limits, reducing hands-on time, limiting random errors and guaranteeing process standardization. (2) Methods: We implemented and validated the complete automation of the SOPHiA GENETICS’ CE-IVD Hereditary Cancer Solution™ (HCS) libraries preparation workflow on the Hamilton’s STARlet platform. (3) Results: We demonstrate that this automated workflow, used for more than 1000 samples achieved the same performances of manual setup in terms of coverages and reads uniformity, with extremely lower variability of reads mapping rate onto the regions of interest. (4) Conclusions: This automated solution offers same reliable and affordable NGS data, but with the essential advantages of a flexible, automated and integrated framework, minimizing possible human errors and depicting a laboratory’s walk-away scenario.

Objectives: The aim of our current study was to analyze whether the use of important measures of methodological quality and reporting of randomized clinical trials published in the field of cardiovascular disease research have changed over time. Further aim was to investigate whether there was an improvement over time in the ability of these trials to provide a good estimate of the true intervention effect. Methods We conducted two searches in the Cochrane Central Register of Controlled Trials (CENTAL) database to identify cardiovascular clinical research trials published in either 2012 or 2017. Randomized clinical trials (RCTs) trials in cardiovascular disease research with adult participants were eligible to be included. We randomly selected 250 RCTs for both publication year 2012 and 2017. Trial characteristics, data on measures of methodological quality and reporting were extracted and risk of bias for each trial was assessed. Results As compared to 2012 in 2017 there were significant improvements in the reporting of the presence of a data monitoring committee (42.0% in 2017 compared to 34.4% in 2012), and a positive tendency of registering cardiovascular disease research RCTs in clinical trial registries (83.6% in 2017 compared to 72.0% in 2012). On the other hand, we also observed that significantly fewer RCTs reported sample size calculation (60.4% in 2017 compared to 98.4% in 2012) in 2017 as compared to 2012. RCTs in 2017 were more likely to have low overall risk of bias ( RoB ) than in 2012 (29.2% in 2017compared to 21.2% in 2012). Conclusion: As compared to 2012 in 2017 there were significant improvement in some, but not all the important measures of methodological quality. Although more trials in the field of cardiovascular disease research had a lower overall RoB in 2017, the improvement over time was not consistently perceived in all RoB domains.

Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms: dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the idea of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the road to the clinic of “one and done” therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

Antiviral therapy such as Oseltamivir has been recommended for hospitalized children with suspected and confirmed influenza for almost 20 years. The therapy is officially authorized for newborns two weeks of age or older, however, questions about its safety and effectiveness still surround it. Our goal was to assess the epidemiological features of two consecutive seasonal in-fluenza cases in children following the COVID-19 pandemic and also to observe the clinical ef-fectiveness and tolerability of oseltamivir in hospitalized children who were not vaccinated against influenza and who had different influenza subtypes, including A (H1N1), A (H3N2), and influenza B, and to identify specific comorbidities associated with influenza in children. We performed an observational study on 1300 children, enrolled between 1st October 2022 and 30th May 2023 and 1st October 2023-4th of May 2024, to the IX Pediatric Infectious Diseases Clinical Section of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș". During the 2022-2023 influenza sea-son, 791 pediatric patients tested positive for influenza and received Oseltamivir. Of these, 89% (704/791) had influenza A, with 86.4% subtypes A(H1N1) and 13.6% of cases had A(H3N2), and influ-enza B 11%(87/791) pediatric patients. Of the total group, 59% were male, and the median age was 2,4 years (1.02-9.28). For the 2023-2024 influenza season, 509 pediatric patients tested positive for influen-za, 56.9% were male gender and were treated with Oseltamivir. 81.6 % had Influenza A, and 18.4% had influenza B. Treatment with neuraminidase inhibitors like Oseltamivir, 2mg/kg/dose twice daily for 5 days, was well tolerated by the children, and we recorded no deaths. The duration of fever hospitaliza-tion after the Oseltamivir administration was significantly longer for patients with A(H1N1) infection than A(H3N2), during both seasons. We identified more complications in the 2022-2023 season and a decreasing number of Influenza B for the 2023-2024 season. Among children with comorbidities, the most common were asthma, gastrointestinal disorders, and metabolic and endocrine diseases. In terms of effectiveness, oseltamivir significantly reduced the intensity of influenza symptoms, thus reducing the number of days of hospitalization (p=0.001) as well as post-infection complications (p=0.005) in both groups. Oseltamivir was less effective in Influenza A (H1N1) than A(H3N2), (p=0.0035). In this study, we evaluated the clinical effectiveness of oseltamivir therapy for all influenza types/subtypes in children, and the length of hospitalization. We identified comorbidities associated with prolonged dura-tion of hospitalisation. Influenza vaccination should be the main tool in the prevention of influenza and its complications in children, especially with comorbidities.

Objective: To examine the burnout syndrome among the healthcare personnel in Puerto Rico during the COVID-19 pandemic. Methods: Descriptive study that pursues to understand burnout syndrome in the clinical personnel in Puerto Rico. The Maslach Burnout Inventory (MBI) was sent via email to healthcare professionals around the island. Furthermore, open questions were asked to the participants. Results: The overall burnout level on the clinical personnel was found to be moderate. Nonetheless, in physicians, 12.1% had severe burnout levels compared to a 13.1% score in nurses. Additionally, 92.4% of physicians and 100% of nurses had moderate to severe burnout. In the three subscales, nurses scored high levels in all of them, and physicians were high in Emotional Exhaustion and moderate level in Depersonalization and Personal Accomplishment at Work. There were high levels of burnout syndrome of the clinical personnel in Puerto Rico. Conclusion: Since the beginning of the COVID-19 pandemic, over 90% of healthcare professionals in Puerto Rico have been working with moderate to severe burnout syndrome, being the nurses the most affected. Key Words: Burnout syndrome, MBI, Clinical personnel, COVID-19, SARS-CoV-2

Objective: The objective of this study is to determine the epidemic dynamics and clinical features of COVID-19 in southern Hainan Island, China, and provide experience for other tropical areas of the world. Methods: This retrospective study included confirmed cases of COVID-19 in southern Hainan. All enrolled patients were treated in Sanya, and data on epidemiological and clinical features of the disease and infection prevention and control measures adopted by the local government during the epidemic were collected. Results: Of the 74 cases, 71 (95.95%) were imported from Wuhan, Hubei Province (47, 63.51%), other cities in Hubei Province (11, 14.86%), or provinces other than Hubei and Hainan (13, 17.57%). Three (4.06%) patients were infected in southern Hainan, including one autochthonous case in Sanya. Fifty-four cases (72.97%) were detected in Sanya, and 27 cases (27.03%) were diagnosed in other cities. The rate of severe or critical cases was 28.38% (21/74), and mortality was 2.7% (2/74). The serum lactate levels and base excess of severe-critical patients were higher than those of patients with mild-moderate disease. Multivariate logistic regression analysis showed that chronic conditions were risk factors for severe and critical COVID-19. Seventy-four patients were diagnosed with COVID-19 over a 22-day period in Sanya, and the epidemic period in the city was 48 days. The outbreak was controlled rapidly because the local government adopted strict infection prevention and control measures. Conclusions: The clinical characteristics of COVID-19 in Hainan Island were similar to those reported in other regions. In Sanya, the rate of severe and very severe cases was higher than in other regions; however, most cases were imported, and there was only one autochthonous case. The rapid control of the outbreak in Sanya may be related to the tropical climate, adoption of strict infection prevention and control measures, daily reporting of new cases, increased public awareness about the epidemic, and other emergency actions implemented by the local government.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis and better prognosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

Background: A growing number of clinical practice guidelines (CPGs) with regards to non-pharmacological interventions for breast cancer survivors are available. However, given the limitations in guideline development methodologies and inconsistency of recommendations, it remains uncertain how best to design and implement such non-pharmacological strategies to tailor interventions for breast cancer survivors with varied health conditions, healthcare needs, and preferences. Aim: To critically appraise and summarise available non-pharmacological interventions for symptom management and health promotion that can be self-managed by breast cancer survivors based on the recommendations of the CPGs. Methods: Clinical practice guidelines which were published between January 2016 and September 2021 and described non-pharmacological interventions for breast cancer survivors were systematically searched in six electronic databases, nine relevant guideline databases, and five cancer care society websites. The quality of the included CPGs was assessed by four evaluators using the Appraisal of Guidelines for REsearch and Evaluation, second edition tool. Content analysis was conducted to synthesise the characteristics of the non-pharmacological interventions that were recommended by the included CPGs, such as the intervention’s form, duration and frequency, level of evidence, grade of recommendation, and source of evidence. Results: Fourteen CPGs were identified and analysed. Of the 14 CPGs appraised, only five were rated as high quality. The domain with the highest standardised percentage was “scope and purpose” (84.61%), while the “applicability” domain had the lowest standardised percentage (51.04%). Five guidelines were assessed as “recommended”, seven were rated as “recommended with modifications”, and the remaining two were considered “not recommended”. Regarding the content analysis, physical activity/exercise, meditation, hypnosis, yoga, music therapy, stress management, relaxation, massage, and acupressure were the common self-managed non-pharmacological interventions recommended by the 14 CPGs. Physical activity/exercise was the only self-managed non-pharmacological intervention that was mostly recommended for psychological and physical symptom management by the included CPGs. However, there were significant disparities in terms of level of evidence and grade of recommendation in the included CPGs. Conclusion: The recommendations for the self-managed non-pharmacological interventions were varied and limited among the 14 CPGs, and some were based on medium- and low-quality evidence. More rigorous methods are required to develop high-quality CPGs in order to guide clinicians in offering high-quality and tailored breast cancer survivorship care.

Older adults with obesity have an increased risk for cognitive decline and subsequent Alzheimer’s disease. Previous research has focused on the impact of individual nutrients and overall dietary patterns to improve cognitive function. The Brain and Body Health (BB-Health) study aims to demonstrate the feasibility of a multicomponent nutritional supplement (MCNS) and weight loss (WL) intervention for individuals with overweight and obesity who are not consuming a healthy diet. BB-Health is a parallel-group randomized placebo-controlled 2x2 factorial pilot trial comparing the MCNS, WL, and MCNS+WL with a Control group. Eligible participants are 55 to 85 years of age with a body mass index 27.0 to 39.9 kg/m2. Major exclusion criteria include type 2 diabetes, moderate or severe cognitive impairment, and self-reported healthy dietary pattern. The BB-Health feasibility trial is registered as NCT05542199 at clinicaltrials.gov. The BB-Health objectives are to report: 1) recruitment and enrollment, including pace and descriptive statistics of the study sample; 2) adherence to the administered interventions; 3) successful data collection and performance of outcome assessments, including evaluation of change in key outcomes over time that are powered for this pilot study; and 4) summary statistics on outcomes for use in planning a subsequent, larger trial. The outcomes of interest are age-sensitive cognitive assessments, cerebral hemodynamics, and related health parameters. All measurements are collected at baseline, 3-, 6-, and 12-month visits. If the BB-Health protocol demonstrates feasibility, the novel MCNS with and without a parallel WL intervention has potential to be administered in a confirmatory randomized trial to evaluate ability to prevent age-related cognitive decline and improve brain health. The BB-Health Feasibility Study could significantly contribute to our understanding of the influence of diet and weight management on cognitive health

Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly in the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.

Biosensors are measurement devices that can sense several biomolecules, and are widely used for the detection of relevant clinical pathogens such as bacteria and viruses, showing outstanding results. Because of the latent existing risk of facing another pandemic like the one we are living due to COVID-19, researchers are constantly looking forward to developing new technologies for diagnosis and treatment of infections caused by different bacteria and viruses. Regarding that, nanotechnology has improved biosensors design and performance through the development of materials and nanoparticles that enhance their affinity, selectivity, and efficacy in detecting these pathogens, such as employing nanoparticles, graphene quantum dots, and electrospun nanofibers. Therefore, this work aims to present a comprehensive review that exposes how biosensors work in terms of bacterial and viral detection, and the nanotechnological features that are contributing to achieving a faster yet still efficient COVID-19 diagnosis at the point-of-care.

Background: Chikungunya virus (CHIKV) diagnosis have become a challenge for primary care physicians in areas where zika virus and/or dengue virus are present. Case definitions for the three arboviral infections are overlapping. Methods: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. Results: 295 patients with confirmed CHIKV infection were included. A screening tool was made using symmetric arthritis (4 points), fatigue (3 points), rash (2 points) and ankle joint pain (1 point). The ROC curve identified a cut-off value and a score ≥ 5.5 was considered positive to identify CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. Conclusion: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.

Background: The different disease forms of cutaneous leishmaniasis (CL) are influenced by parasite and host factors. Malnutrition impairs immunity. It has been found to disrupt immune protection by favoring the production of anti-inflammatory prostaglandins over pro-inflammatory cytokines. In Ethiopia, data on CL patients’ nutritional status remains scarce. This study aims to assess clinical polymorphism and its association with the nutritional status of the patient. Methods: A retrospective study conducted from June to July 2024, and patient’s data was analyzed from those treated for CL. Nutritional status was assessed through MUAC, Z-score, and BMI. Results: A total of 217 CL patient’s statuses were nutritionally defined and 22% of them were found malnourished. Most of the CL problems concentrate on age <18 years and found mainly affected groups than others 23 (27%). Malnutrition explained more in MCL (30%) and Repeat/recurrent patients (38.5%) than in LCL (20%) and new CL cases (21%) respectively. In Early disease onset, the malnutrition level was higher than in later times (29%) versus (17%). Conclusions: The burden of Malnutrition is high in CL patients and might modify the clinical variability like CL forms, treatment response, and polymorphism of the disease.

Pulmonary thromboembolism is a very common cardiovascular disease, with a still high mortality rate. Despite the clear guidelines, this disease still represents a great challenge both in diagnosis and treatment. Heterogeneous clinical picture, often without pathognomonic signs and symptoms, represents a huge differential diagnostic problem even for experienced doctors. The decision on the therapeutic regimen also represents a major dilemma in the group of patients who are hemodynamically stable at initial presentation and have signs of right ventricular (RV) dysfunction proven by echocardiography and positive biomarker values (pulmonary embolism of intermediate-high risk). Studies have shown conflicting results about the benefit of using fibrinolytic therapy in this group of patients until hemodynamic decompensation, due to the risk of major bleeding. The latest recommendations give preference to new oral anticoagulants (NOACs) compared to vitamin K antagonists (VKA), except for certain categories of patients (patients with antiphospholipid syndrome, mechanical valves, pregnancy). When using oral anticoagulant therapy, special attention should be paid to drug-drug interactions, which can lead to many complications, even to the death of the patient. Special population groups such as pregnant women, obese patients, patients with antiphospholipid syndrome and cancer represent a great therapeutic challenge in the application of anticoagulant therapy. In these patients, not only the effectiveness of the drugs must be taken into account, but great attention must be paid to their safety and possible side effects, which is why a multidisciplinary approach is emphasized in order to provide the best therapeutic option.

Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials.gov - NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared intensive behavioral treatment intervention condition (IC) with control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n=88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n=88) received only the brochure. Participants were assessed at baseline and day-22 follow-up. Self-reported chewing status at day-22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. Results: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p=0.0058, which met the Stage 3 criteria for significance and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). Conclusion: Robust self-reported intervention effects at day-22 suggests that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.

There is a growing number of evidence-based indications for pharmacogenetic (PGx) testing. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. In an observational cohort study we included subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. PGx-guided pharmacotherapy management was supported by the PGx expert system SONOGEN XP. The primary study outcome was PGx-based changes and recommendations regarding current and potential future medication. PGx-testing was triggered by specific drug-gene pairs in 102 subjects, and by screening in 33. Based on PharmGKB expert guidelines we identified at least one “actionable” variant in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized expert consultations with interdisciplinary collaborations.

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder, is increasingly diagnosed and significantly affects communication, behavior, and social interaction. The current diagnostic framework, guided by the DSM-5, has limitations that may lead to clinical gaps due to overlapping symptoms of ASD and other disorders. This study proposes a comprehensive approach to enhance ASD diagnosis through clinical stratification based on comorbidities. We applied precision medicine techniques to identify and categorize ASD into ten clinical profiles. Our findings contribute to a more profound understanding of ASD, including its varied clinical manifestations and comorbidities, and facilitate the development of personalized therapeutic strategies.

Orthohantaviruses can cause two types of human infections: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). HFRS is a zoonotic disease transmitted by multiple rodent species. Yunnan Province in southwest China is the natural foci of HFRS, and Dali Prefecture in Yunnan Province has the highest incidence of HFRS; however, the precise status of orthohantavirus infection in Dali Prefecture remains unknown. To this end, we obtained clinical data of HFRS patients from the medical records of the People's Hospital of Xiangyun County in Dali Prefecture from July 2019 to August 2021. We collected epidemiological data of HFRS patients through interviews and investigated host animals using the night clip or night cage method. We systematically performed epidemiological analyses of patients and host animals. The differences in the presence of rodent activity at home (2=8.75, P=0.031&lt;0.05), of rodent-proof equipment in the food (2=9.19, P=0.025&lt;0.05), and of rodents or rodent excrement in the workplace (2=10.35, P=0.014&lt;0.05) were statistically different in the four clinical types, including mild, medium, severe, and critical HFRS-associated diseases. Furthermore, we conducted molecular detection of orthohantavirus in host animals. The total orthohantavirus infection rate of rodents was 2.7% (9/331); the specific infection rate of specific animal species was 6.1% (5/82) for the Apodemus chevrieri, 100% (1/1) for the Rattus nitidus, 3.8% (2/53) for the Rattus norvegicus, and 12.5% (1/8) for the Crocidura dracula. In this study, a total of 21 strains of orthohantavirus were detected in patients and rodents. The 12 orthohantavirus strains from patients showed a closer relationship with Seoul orthohantavirus (SEOOV) L0199, DLR2, and GZRn60 strains; the six orthohantavirus strains from Rattus norvegicus and Apodemus chevrieri were closely related to SEOOV GZRn60 strain; One strains (XYRn163) from Rattus norvegicus and one strain (XYR.nitidus97) from Rattus nitidus were closely related to SEOOV DLR2 strain; the orthohantavirus strain from Crocidura dracula was closely related to the Luxi orthohantavirus (LUXV) LX309 strain. In conclusion, patients with HFRS in Xuangyun County of Dali Prefecture are predominantly affected by SEOOV, with multiple genotypes of orthohantavirus in host animals, and most importantly, these orthohantavirus strains constantly demonstrated zoonotic risk in humans.

Circulating miRNA-451a has recently emerged as an important biomolecule with potential clinical values as a diagnostic marker for several diseases. However, to be used as such, it is critical to accurately assay miRNA-451a in the clinic. Yet, pre-analytical factors that can affect such an error-free clinical assay of miRNA-451a have not been explored. This study aimed at investigating several of these pre-analytical factors that may affect the accurate quantification of miRNA-451a in human blood samples. We initially evaluated miRNA-451a levels in red blood cells (RBCs), white blood cells (WBCs), platelets, and plasma by droplet digital PCR (ddPCR). Next, we quantified miRNA-451a levels in whole blood or plasma stored at different temperatures for different time periods by ddPCR and used hemolyzed plasma samples to study the effects of hemolysis on plasma miRNA-451a concentration. We found that WBCs and platelets contain trace amounts of miRNA-451a and that about 99.9% of miRNA-451a in the blood are localized in RBCs. Hemolyzed plasma showed 58.5-fold increase in miRNA-451 concentration as compared to non-hemolyzed plasma. Importantly, plasma stored at room temperature (RT) or 4ºC showed a steady statistically significant decrease in miRNA-451a levels over a 7-day period whereas plasma samples stored at -20 or -80ºC for up to 7 days showed stable miRNA-451a levels. Together, our data indicate that hemolysis and blood storage at RT or 4ºC may have significant negative effects on the levels of circulating miRNA-451a.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

Aim: The overall aim of the study was to assess the reasons and experiences of participants involved in Antibody Mediated Prevention (AMP) HIV prevention clinical trial at University of North Carolina (UNC) Project, Lilongwe, Malawi. We determined the participants’ reasons for participating in HIV Prevention clinical trials; and the experiences of participants in HIV Prevention clinical trials. Methods: We adopted the qualitative cross-sectional study method. Data were collected using in-depth interviews (IDIs). Purposive sampling was used to select 12 study participants who consented to take part in the study. All participants were the ones taking part in the AMP HIV prevention study at the UNC Project. Data analysis was done concurrently with data collection using content analysis. Results: Individuals were motivated to participate in HIV research due to a range of perceived benefits. These included personal, health, and financial benefits. Participants' research experiences and their continued participation in HIV research were influenced by the research clinic context and the nature of their interactions with research staff. Conclusion: When the clinical trial study participants’ expectations are met through what they experience in the study, the chances of them adhering to the study visits and procedures are high. Even for those who did not have any expectations prior to the study, feeling welcomed and being able to open up to the study staff encouraged their continued participation. In the end, this outweighed the negative comments made by the people in their communities or their friends

Modern medicine adopted four presumptions when it evolved from ancient experienced-based mind-body medicine. To understand its failure in finding cures for chronic diseases, we examined four presumptions, and found that statistical population of health properties does not exist for most research purposes, mathematical models are misused to model intensive properties, synthetic drugs are inherently more dangerous than nature-made medicines under their respective application conditions, and reductionist treatments are inferior and inherently dangerous. We found that clinical trials are valid only for research where treatment effect is much stronger than the total effects of all interfering or co-causal factors or errors introduced by misused mathematical models can be tolerated. In all other situations, clinical trials introduce excessive errors and fail to detect treatment effects, or produce biased, incorrect or wrong results. We further found that chronic diseases are manifestation of small departures in multiple process attributes in distinctive personal biological pathways networks, that modern medicine lacks required accuracy for accurately characterizing chronic diseases, and that reductionist treatments are good at controlling symptoms and safe for short term uses. For all stated reasons, as long as modern medicine continues relying on the flawed presumptions, it can never find predictable cures for chronic diseases. By implication, predictable cures to chronic diseases are adjustments to lifestyle, dietary, emotional, and environmental factors to slowly correct departures in process attributes responsible for chronic diseases.

Rationale: A wide range of bioactive phytoconstituents from edible fungi, especially therapeutic mushrooms, have the potential to improve health, especially in the case of chronic illnesses. Known for its anti-cancer qualities, ganoderma lucidum has been the focus of multiple clinical studies. Existing systematic reviews imply that more clinical research and methodological refinement are necessary to support its usage as a primary cancer treatment.Objective: The objective of this research is to evaluate the anti-cancer potential of the bioactive phytoconstituents found in mushrooms, specifically Ganoderma lucidum, in a thorough manner. The aim is to conduct a critical assessment of the extant literature, pinpoint any deficiencies, and offer valuable perspectives on the methodological excellence and research requirements in this domain.Method(s): A thorough analysis of published clinical trials was carried out, with a focus on studies that examined the effectiveness of Ganoderma lucidum and other products derived from mushrooms in treating cancer. The study's design, stated results, and methodological rigor were all carefully examined to evaluate the validity and reliability of the conclusions.Results: Despite Ganoderma lucidum's potential against cancer, the evaluation finds insufficient data to support its widespread usage as a primary cancer treatment. Products made from mushrooms, which are frequently sold as dietary supplements, have anti-cancer claims. But since pre-approval is not required under US regulatory framework in order to market food supplements, these statements raise questions regarding their scientific validity.Conclusions/Recommendations: The study's result emphasizes the necessity of more methodological advancement in clinical studies examining Ganoderma lucidum's potential as an anti-cancer agent. It also highlights the significance of thorough scientific validation for goods made from mushrooms that make health claims. To establish accurate claims regarding their anti-cancer effects, recommendations include developing technological methods for the purification of bioactive substances and undertaking thorough studies of mushroom products from different geographical regions. The goal of this thorough analysis is to direct future investigations and support the ethical promotion and use of products derived from mushrooms for medical purposes.

The coronavirus disease 2019 (COVID-19) is a novel global pandemic infectious disease with higher potential for outbreaks than the other epidemic disease such as severe acute respiratory syndrome (SARS), influenza A (H1N1), and the Middle East respiratory syndrome (MERS), which identified in China on December 31, 2019. This disease is caused by a new generation of betacoronavirus termed as the 2019 novel coronavirus (2019-nCoV) or SARS-CoV-2. Although, the first report of this disease was in recent months, now, the COVID-19 is known as a global pandemics. Hence, the aim of this article is the quick review of the recent studies on the novel coronavirus disease 2019 including researches on the epidemiological parameters, mechanism of action, diagnosis, and treatment of the novel coronavirus disease, as well as clinical features of patients infected with COVID-19. Moreover, the novel COVID-19 has comprised of SARS, H1N1, and MERS.

Background: One way to demonstrate the existence of nursing is to develop a nursing theory model through nursing research which can ultimately be implemented in nursing practice. RAM is one of the most frequently used models in guiding nursing research. Roy's Adaptation Model (RAM) is one of the most useful conceptual frameworks that guide nursing practice, direct research, and influence education. Theory-guided nursing practice is fundamental in providing the framework for developing superior and quality nursing care.Objectives: This systematic review aims to critically analyze recent studies using RAM as a conceptual framework to identify the effectiveness of this model in guiding nursing research.Methods: A literature search was conducted on five databases, namely SCOPUS, PubMed, ProQuest, ScienceDirect, and SAGEPub. There were no population boundaries and diagnoses involved in the study. The study is a quantitative design focused on publication between 2015-2021. The methodological quality of applying the Cochrane and JBI bias tools. The analysis uses narrative synthesis.Results: 20 studies were found out of 1,315 studies. The research population found is very diverse. The given intervention follows the conceptual framework of RAM. RAM-based interventions effectively overcome the problems experienced by patients and reduce the perceived symptoms and improve the patient's quality of life.Conclusion: The conceptual use of RAM theory in nursing research has been widely reported. RAM-based interventions have a significant impact and have strong evidence-based practice in improving patient health status.

Objectives: Human herpes viruses can cause life-threatening diseases in immunocompromised children, especially leukemic patients. Therefore, the aim of this study is to detect the human herpes viruses (HHV1-7) and to investigate its clinical significance in Middle Eastern Pediatric Leukemia Patients by using 2 Independent PCR assays. Methods: Detection of human herpes virus DNA has been done in blood samples of 200 pediatric leukemia patients in addition to 90 blood donors as a control group using multiplex PCR assays. When a ‘‘positive’’ result was observed, real-time PCR was performed to measure the viral load. Results: The most frequent herpes virus infection in Middle Eastern Pediatric Leukemia cases was CMV, followed by EBV, then HHV6, VZV, HHV7, HSV1, and HSV2, where they were 92/200 (46%), 76/200 (38%), 72/200 (36%), 48/200 (24%), 12/200 (6%), 8/200 (4%), and 2/200 (1%) respectively. Also, there was a statistically significance difference between leukemic patients and their controls regarding CMV, EBV, HHV6, and VZV (P <0.05). Correlation between percentage of co-infection, and clinical parameters for the 7 herpes viruses has been studied, and there is an increase in absolute neutrophilic count (ANC), total leukocyte count (TLC) and duration of fever and neutropenia in age group 6-11 years for HHV6/CMV, then in age group 12-18 years especially for EBV/CMV and CMV/HHV6. Also, our results show that multiplex PCR assay is close to single PCR assay in relation to specificity and sensitivity which in turn prove its validity for early diagnosis of herpes viral infection. Conclusions: Adopting multiplex PCR technique is helpful in screening of virus infections. It will save time, effort, cost effective and will assist in rapid diagnosis. However, the clinical relevance of the virus infection needs to be evaluated by quantitative real-time PCR which in turn will help patient's management by using appropriate antiviral treatment.

Cyclic vomiting syndrome (CVS) is a frequently disabling condition defined by severe, discrete, stereotypical episodes of nausea and vomiting. In our previous report [1], a candidate gene list was evaluated in a group of 80 unrelated participants with CVS with extensive genetic sequencing (whole exome/genome). Twenty-two good candidate genes for CVS association were identified, from which a cellular model of aberrant cation transport and energy metabolism was proposed. Herein, we present additional clinical information on those 80 participants, including eight case reports to highlight general principles and clinical practices. Our participants demonstrate substantial phenotypic and genotypic heterogeneity in CVS, including a propensity for specific co-morbidities in the participants and relatives, evolution towards episodes in which vomiting is less apparent, labeling with “non-organic” diagnoses, multiple genes, polygenic inheritance, and association with variants not designated as Pathogenic. Our case reports illustrate how genetic information can guide clinical management and argue to the high clinical utility of appropriate genetic testing and analysis in CVS. Expression profiling of our 22 candidate genes suggests an anatomical model in a unit defined by vagal afferents and adjacent cells. Our models are consistent with multiple current hypotheses of CVS and the efficacy of commonly-recommended treatments.

CGP do not substantially differ between initial tumor vs tumor recurrence and recurrent thymomas vs non-recurrent thymomas. Cell-cycle control genes alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored.

This study was aimed to examine the recent trends of antibiotic resistance (AR) prevalence in Staphylococcus aureus isolated from milk of animals with clinical mastitis in areas of the Abruzzo and Molise regions in central Italy. Fifty-four S. aureus isolates could be obtained from routine testing for clinical mastitis agents carried out in the author institution in years 2021 and 2022. These were analyzed for phenotypic resistance to eight antibiotics recommended for testing by European norms and belonging to the antibiotic classes used for mastitis treatment in milk producing animals. Moreover, the presence of 14 transferable genetic determinants encoding resistance to the same antibiotics was analyzed by qPCR tests developed in this study. Phenotypic resistance to non-β-lactams was infrequent, with only one 2022 isolate resistant to clindamycin. However, low level resistance to the β-lactam cefoxitin was observed in 59.2% isolates in both years making these isolates classifiable as methicillin resistant. The AR genotypes detected were blaZ gene (50% 2021 isolates and 44.4% 2022 isolates), ermC/T- aphA3-blaZ (one 2021 isolate), ant6-ermC/T-aphA3-blaZ (one 2021 isolate), ermB-blaZ (one 2022 isolate) and mecA-mph (one 2022 isolate). An interview to the veterinarians who conferred the samples, regarding antimicrobials prescribed for mastitis treatment and criteria of usage, indicated a possible causal relation with the AR test results. The low prevalence of AR genotypes, not increasing in time, most probably reflecting the reported management of antibiotic therapies in farms. However, the frequently observed cefoxitin resistance needs to be explained genotypically, further monitored and limited by modifying antibiotic usage practices. The identification of a mecA positive isolate in 2022 suggests to investigate further if this genotype is emerging locally.

Efficient commencement of clinical trials is pivotal for their successful execution. The purpose of this study was to determine and examine the factors that contribute to trial start-up delays. The study assessed 20 clinical trials' start-up stages in order to identify relevant variables. Results showed that trials with an emphasis on devices, trials that did not outsource, trials that utilized less auxiliary services, and trials that employed interventional designs had quicker start-up times than observational studies. Furthermore, approval times were substantially shortened by using a centralized Institutional Review Board (IRB) rather than a local IRB. Furthermore, compared to studies that successfully enrolled subjects, those who failed to do so required more time to complete contracts and budgets and secure IRB clearance. This study underscores the diverse impact of clinical trial features on start-up timelines. Understanding these factors is crucial for optimizing the initiation process of clinical trials.

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcomes measures selected: the myostatin inhibition story thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models has failed to translate into clinical benefit to patients has been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.

Clinical agreement between two quantitative measurements on a group of subjects is generally assessed with the help of the Bland-Altman (B-A) limits. The interpretation regarding agreement is based on whether B-A limits are within the pre-specified clinical tolerance. Thus, clinical tolerance limits are necessary for this method. We argue in this communication that such limits of clinical tolerance can be directly used for assessing agreement and plead that this nonparametric approach is simple and robust to the distribution pattern and outliers. Such direct use of clinical tolerance limits has more flexibility, and it is more effective in assessing the extent of agreement.

The clinical neurophysiological tests allow determine the type, extent, and nature of brachial plexus damage. They are crucial in decision-making regarding surgical procedures or conservative treatment. This report aimed to present an algorithm for rehabilitation procedures in patients with brachial plexus injury of various origins based on the results of neurophysiology findings for the selection of procedures supporting the process of nerve and muscle regeneration. The research group consisted of patients whose medical documentation was analyzed concerning the reason, level, and localization of damage to the brachial plexus structures, surgical and or rehabilitative treatment as well as the MRI results. Among the group of ten patients, the clinical studies showed the greatest incidence of brachial plexus injuries of the mixed (both pre- and postganglionic), all trunks, and cervical root injuries, respectively. Results of the motor evoked potentials (MEP) and electroneurography (ENG) recordings induced at levels of spinal roots and Erb's point showed a decrease of more than 40% in amplitudes on the symptomatic side in comparison to the asymptomatic side. This difference was recorded for the axillary and radial innervation and the C5, C6, and C7 root domains, ranging from 56% to 71%; the lowest decrease was recorded following electrical stimulation at Erb's point for the ulnar nerve (41.5%). The latency prolongation on the symptomatic side in CMAP and MEP tests ranged from 0.2 to 1.9 ms, the most following magnetic stimulation of the C5 cervical root for the axillary innervation. All results indicated the axonotmesis and neuropraxia type of injury in motor fibers (40%) confirmed by EMG results. The sensory conduction studies (SNCS) in distal nerve branches did not confirm the severe advancement of the brachial plexus injury (22%). The proposed algorithm of the physiotherapeutic procedures should be mainly targeted for recovery of motor dysfunction as the consequence of brachial plexus injury. Rehabilitation should incorporate the treatment supporting nerve regeneration, muscle strengthening, and maintaining functional ranges of motion of the injured extremities. The rehabilitation treatment for patients with brachial plexus injuries is an individualized process, and the selection of procedures and the effectiveness of the treatment undertaken should be confronted with results of neurophysiological tests verifying the motor neural transmission from the level of the cervical motor center to the effector, peripheral nerve function, and muscle’s motor unit activity.

Lung cancer, globally recognized as the leading cause of cancer-related mortality, presents a pressing need for innovative treatment strategies. Increasing evidence points towards the potential of monoamine oxidase (MAO) inhibitors in modulating cancer progression, primarily due to their role in regulating cellular metabolism and apoptotic pathways. This extraordinary study delves into the multifaceted therapeutic implications of MAO inhibitors in lung cancer management, elucidating their ability to pave the way for clinical advancement via novel targets and pathways. Capitalizing on recent advances in molecular biology, this research explores the molecular mechanisms underlying the anticancer actions of MAO inhibitors. By examining their impact on cell proliferation, migration, invasion, and apoptosis in lung cancer cell lines, we provide insight into the intricate signaling pathways and biochemical processes modulated by these compounds. The study also investigates the synergistic effects of MAO inhibitors in combination with established chemotherapeutic agents, elucidating their potential to enhance treatment efficacy and reduce cytotoxicity. Furthermore, we delve into the implications of MAO inhibitors on the tumor microenvironment, evaluating their influence on angiogenesis, immune regulation, and the epithelial-mesenchymal transition. This comprehensive analysis enables the identification of novel molecular targets, which hold promise for the development of advanced therapeutics tailored for specific lung cancer subtypes. To substantiate our findings, in this review, we thoroughly analyze the existing literature using state-of-the-art bioinformatics tools." in vivo orthotopic lung cancer models, and clinical patient cohorts. This robust and multidisciplinary approach permits the generation of clinical evidence supporting the integration of MAO inhibitors in lung cancer management. Conclusion: This ground-breaking study establishes the therapeutic potential of monoamine oxidase inhibitors in lung cancer management by unearthing novel pathways and targets for clinical advancement. The outcomes open doors for the development of innovative treatment strategies and inspire continued research efforts to combat the global burden of lung cancer.

Objective: To analyze the clinical and economic impact of community-onset urinary tract infections (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae requiring hospitalization. Methods: A retrospective cohort study included all adults with UTI caused by K. pneumoniae admitted to a tertiary care hospital in Barcelona, Spain, between 2011 and 2015. Demographic, clinical and economic data were analyzed. Results: One hundred and seventy-three episodes of UTI caused by K. pneumoniae were studied; 112 were non-ESBL-producing and 61 ESBL-producing. Multivariate analysis identified ESBL production, acute confusional state associated with UTI, shock, and time to adequate treatment as risk factors for clinical failure during the first 7 days. Economic analysis showed differences between ESBL-producing and non-ESBL-producing K. pneumoniae for the total cost of hospitalization per episode (mean 6,718 € vs 3,688 € respectively). Multivariate analysis of the higher costs of UTI episodes found statistically significant differences for ESBL production and time to adequate treatment. Conclusion: UTI caused by ESBL-producing K. pneumoniae requiring hospitalization, and time to adequate antimicrobial therapy are associated with worse clinical and economic outcomes.

Standardised forms for capturing clinical data promote consistency in data collection and analysis across study sites, enabling faster, higher-quality evidence generation. ISARIC and the World Health Organization have developed case report forms (CRFs) for the clinical characterisation of several infectious disease outbreaks. To improve the design and quality of future forms, we analysed the inclusion and completion rates of the 243 fields on the ISARIC-WHO COVID-19 CRF. Data from 42 diverse collaborations, covering 1,886 hospitals and 950,064 patients were analysed. A mean of 129.6 fields (53%) were included in the adapted CRFs implemented across the sites. Consistent patterns of field inclusion and completion aligned with globally recognised research priorities in outbreaks of novel infectious diseases. Outcome status was the most highly included (95.2%) and completed (89.8%) field, followed by admission demographics (79.1% and 91.6%), comorbidities (77.9% and 79.0%), signs &amp; symptoms (68.9% and 78.4%) and vitals (70.3% and 69.1%). Mean field completion was higher in severe patients (70.2%) than in all patients (61.6%). The results indicate that clinical characterisation CRFs can be streamlined to reduce data collection time, including the modularisation of CRFs to offer a choice of data volume collection and the separation of critical care interventions. This data-driven approach to designing CRFs enhances the efficiency of data collection to inform patient care and public health response.

Parkinson's Disease (PD) is a neurodegenerative disorder that affects the motor system of the human body. Currently, the available treatments are limited and often have undesirable side effects. In this context, the aim of this study was to develop a novel combinational formulation of Apomorphine and Quetiapine and evaluate its efficacy in a rat model of PD. The formulation was prepared using the solvent evaporation technique and characterized for its physicochemical properties. The in-vitro drug release was evaluated using the Franz diffusion cell method, and the pharmacokinetics of the combination was studied in rats. The behavioural and biochemical parameters were evaluated in the rats using the Rotarod, pole test, and biochemical assays. The results showed that the developed formulation had satisfactory physicochemical properties and exhibited sustained drug release. The pharmacokinetic studies showed that the combination exhibited a longer residence time than the individual drugs. The behavioural and biochemical parameters showed that the combination was effective in improving motor function and reducing oxidative stress. In conclusion, the developed Apomorphine and Quetiapine combination formulation showed promising results in improving motor function and reducing oxidative stress in rat model of PD. Further studies are required to evaluate the safety and efficacy of the developed formulation in humans.

Background: Absolute uterine factor infertility (AUFI) is a kind of infertility that is completely attributable to uterine absence (surgical or congenital for women with Mayer-Rokitansky-Küster-Hauser syndrome: MRKH) or anatomic or functional abnormality that prevents embryo implantation or completion of pregnancy to term. Until recently, the only viable option to parenthood for couples with AUFI were adoption or surrogacy. Since a first attempt of uterus transplant (UTx) in 2000, nine babies were born from women with a transplanted uterus from 2014, eight of which in Sweden, and one in the United States. These promising results are raising immense hopes for the women with AUFI and there is optimism about the possibility for UTx to become part of clinical care even though, besides encouraging results, the procedure has also resulted in increased risks and harms for both the donors and recipients and increased risks of premature birth for the fetus. At present UTx is still considered as experimental and requiring more research and safety assessment before becoming a therapeutic option for AUFI. The transition from experimental procedure to therapeutic care would result in less strict ethical scrutiny for UTx and in the possibility for patients to get reimbursement for the procedure by the relevant healthcare insurance or public healthcare providers. In turn, an increase in the number of UTx performed yearly by specialized surgical teams would result in a general improvement of the “field strength”. However, at present it is difficult to establish the amount of evidence that we need in order to consider UTx as no longer experimental but routine clinical practice. The literature on UTx provides recommendations on the different outcomes that should be monitored in this experimental phase but no study is anticipating the number of subjects that should be followed and for how long. Conclusion: As for other transplants that have become routine practice, like renal transplant and heart transplant, it is likely that the decision on “routine practice readiness” will result from available cumulated evidences, from expert capacity to find a consensus on best practices and on political considerations as well, including pressures form patients and patient groups.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

Meta-analysis of plant sterol supplement studies suggests an 8% lowering of LDL cholesterol for 2 to 2.5g/day of plant sterols. Cereal foods have been rarely tested and one study showed a lower LDL lowering of 5.4% with 1.6g of plant sterol in breakfast cereal. We aimed to test a breakfast wheat biscuit with 2g of plant sterols in a single serve of two wholegrain wheat breakfast cereal biscuits. Fifty volunteers with a total cholesterol of >5.5mmol/L were recruited for a randomised crossover study with two 4-week periods with no washout of which 45 successfully completed the study. After exclusion of four outliers the difference in LDL cholesterol between standard wholegrain wheat breakfast cereal biscuit and plant sterol-enriched wholegrain wheat breakfast cereal biscuit was 0.23 mmol/L or 5.6% (P=0.001) with a 95% confidence interval of 2.4-8.9%. Men and daily cereal consumers had greater responses 9.8% vs 3.6% and 7.2% vs 3.8% respectively (P<0.05). The LDL lowering effect of 2g of plant sterol enriched from one serve of wholegrain wheat breakfast cereal biscuit was not significantly different from other food products delivering 2-2.5g of plant sterols daily. Regular cereal consumers have a better response.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

Artificial Intelligence (AI) is revolutionizing decision-making procedures in healthcare information systems (HIS), increasing the efficacy, accuracy, and personalization of healthcare. Notwithstanding remarkable progresses, yet there remain gaps in the holistic comprehension and implication of AI-driven technologies across various HIS scenarios. These gaps, consisting limited integration of AI across a variety of HIS parts and inadequate emphasize on interpretability and privacy, motivate our study to conduct a structured evaluation of recent AI applications in this domain. In this study, we present a novel taxonomy for the AI implication in medical decision-making. We analyzed 30 articles and categorized them into six groups including: Clinical Decision Support Systems (CDSS), Predictive Analytics, Natural Language Processing (NLP), Computer-Aided Diagnostics (CAD), Robotic-Assisted Surgery, and Virtual Health Assistants (VHAs/chatbots). Our study aims to propose a holistic perspective of the fast evolving perspective of AI in HIS. The majority of the investigated studies were published from 2023 and 2022, with Springer as the leading publisher (33%). Python and MATLAB were the most well-known simulation languages, applied in 48% and 20% of the papers, respectively, reflecting the technical trends in the area. By emphasizing on pivotal criteria like interpretability, accuracy, and privacy, this research aims to elucidate the crucial issues and development driving AI-driven decision-making in HIS.

Thromboprophylaxis of hospitalized patients at risk of venous thromboembolism (VTE) presents challenges owing to patient heterogeneity and lack of adoption of evidence-based methods. Intuitive practices for thromboprophylaxis have resulted in many patients being inappropriately prophylaxed. Multiple interventions for thromboprophylaxis have been tested, including use of multifaceted approaches such as national VTE prevention programs with audits, use of passive alerts (either human or electronic), and more recently use of active clinical decision support (CDS) tools incorporated into electronic health records (EHRs). Multifaceted health-system interventions have shown mixed results in their ability to increase appropriate thromboprophylaxis and reduce VTE, unless mandated through a national VTE prevention program, though the latter approach is potentially costly, effort- and time-dependent. Studies utilizing passive human or electronic alerts have also shown mixed results in increasing appropriate thromboprophylaxis and reducing VTE. The use of active CDS tools holds the greatest promise, especially with further refinement and widespread implementation within various EHRs and clinical workflows. Recent-ly a universal cloud-based and EHR-agnostic CDS VTE tool revealed high adoption and effectiveness in increasing appropriate thromboprophylaxis and reducing major thromboembolism. This narrative review summarizes the literature on system-wide thromboprophylaxis interventions in hospitalized patients, with a focus on CDS tools.

In hepatocellular carcinoma (HCC), recurrence usually occurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce recurrence rates. In this report, the in vivo mouse effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance was evaluated. A phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in HCC recurrence in patients who have undergone curative surgery for HBV-related HCC. In animal modeling, HBV suppression was significantly greater with rmIFN-α and anti-PD1 sequential combination treatment than with their treatment alone. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks at the dose of 450 µg for six doses, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease or clearance of HBV surface antigen was observed in two patients. Dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was determined. Currently no HCC recurrence has been observed. The treatment modality was well tolerated. The data support further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

Background: Best Possible Medication History (BPMH) collected by clinical pharmacists is crucial for effective medication review but, in Italy, it is often left to the nursing staff. This study aims to compare the quality and accuracy of a clinical pharmacist-documented BPMH with the current standard practice of ward staff-collected BPMH at an Italian perioperative surgical setting. Methods: A 20-week prospective observational non-profit study was conducted in a major University hospital. The study comprised a feasibility, an observational, and an interventional phase. During the feasibility phase, 10 items for obtaining a correct BPMH were identified. The control group consisted of retrospectively analyzed BPMHs collected by the ward staff during the observational phase, while interventions included BPMHs collected by the clinical pharmacist during the third phase. Omissions between the two groups were compared. Results: 14 (2%) omissions were found in the intervention group, compared with 400 (57.4%) found in the controls (p<0.05); data collection was more complete when collected by pharmacists compared to the current modalities (98.0% versus 42.6%; p<0.05). Conclusions: The involvement of a pharmacist significantly reduced the number of omissions in perioperative surgical-collected BPMHs. This intervention holds the potential to decrease the risk of medication errors associated with inaccurate or incomplete BPMHs prior to surgical hospitalization.

AK is a common precancerous skin condition that requires effective detection and treatment monitoring. To improve the monitoring of AK burden in clinical settings with enhanced automation and precision, the present study evaluates the application of semantic segmentation based on the U-Net architecture (AKU-Net). AKU-Net employs transfer learning to compensate for the relatively small dataset of annotated images and integrates a recurrent process based on convLSTM to exploit contextual information and address the challenges related to low contrast and ambiguous boundaries of AK-affected skin regions. We used an annotated dataset of 569 clinical photographs from 115 patients with actinic keratosis to train and evaluate the model. From each photograph, patches of 512x512 pixels were extracted using translation lesion boxes that encompass lesions in different positions and capture different contexts of perilesional skin. In total, 16488 translation augmented crops were used for training the model, and 403 lesion center crops were used for testing. To demonstrate the improvements in AK detection, AKU-net was compared with plain U-Net and U-Net++ architectures. The experimental results highlighted the effectiveness of AKU-Net, improving both automation and precision over existing approaches, paving the way for more effective and reliable evaluation of actinic keratosis in clinical settings.

The importance of frailty in older people is getting constant recognition as an important aspect both in terms of public health, as well in personal level for the appropriate management of an older person health condition. This is reflected by the continuously increasing number of research studies carried out in several settings across different countries. Sometimes this is very solid, but in other cases there is a considerable gap in terms of accurate and well grounded documentation of frailty status. This is the case in Greece, where we are missing clinically validated tools to approach frailty. We are missing frailty screening tools, such as for instance PRISMA 7, the gold standard tool of Fried criteria is somehow problematic since the question referring to physical activity originates from a questionnaire that has not been translated and validated, while Clinical Frailty Scale has been validated for the translation but not for the capacity to detect frailty. Aim of this study is to validate these tools for their accuracy to detect frailty by using a measurable index of frailty, previously proposed for use in clinical studies: the Short Physical Performance Battery (SPPB). 74 male and female participants have been evaluated for their frailty status using different tools. We observed that PRISMA 7 translation detects frailty only when one question is removed at a cut-off of ≥ 2 and indicated a sensitivity of 88.1%, and specificity of 99.9% with a good correlation with SPPB measurements (r = 0.858; p &lt; 0.001). When CFS was validated using SPPB it demonstrated a very good correlation (r = -0.838; p &lt; 0.001 respectively) as it was the case for the modified Fried Criteria (r = -0.725; p &lt; 0.001). All items demonstrated a good correlation between them. We can here propose that we can accurately assess frailty status in the community setting by using a modified version of Fried criteria, Clinical Frailty Scale translation in Greek and we can screen for frailty by using the Greek translation of PRISMA 7 only after removing the item 6 of the questionnaire.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

This retrospective study aimed to assess coronary artery calcium (CAC) progression in serial computed tomography measurements according to risk factor changes. In 448 asymptomatic adults who underwent CAC measurements with more than one-year intervals, CAC progression was assessed according to age, sex, variable traditional risk factors (diabetes mellitus, hypertension, hyperlipidemia, and smoking), and initial CAC score (0, 0.1–100, and &gt;100). Univariate and multivariate logistic regression analyses were assessed for independent predictors of rapid CAC progression (△CAC/year&gt;20). During the 3.5-year follow-up, coronary artery calcifications occurred in 43 (12.8%) of 336 individuals with an initial CAC score of zero. Of 112 individuals with initial CAC presence, 60 (53.6%) had △CAC/year&gt;20. Age, male sex, body mass index, and all risk factors were significantly associated with △CAC/year&gt;20, but recently diagnosed hypertension (odds ratio [OR], 11.3) and initial CAC score (OR, 1.05) were significant independent predictors in multivariate regression analyses. CAC progression was affected by demographic and traditional risk factors, but adjusting for these factors, recently diagnosed hypertension and initial CAC score were the most influential factors for rapid CAC progression. These findings suggest that patients with higher initial CAC scores may benefit from more frequent follow-up scans and checks regarding risk factor changes.

We performed electronic research for articles published in PubMed, MEDLINE, and ScienceDirect databases from January 2004 to January 2023. The systematic review of twenty (20) peer-reviewed articles about dosimetric parameters and eight (8) articles about clinical outcomes confirmed the dosimetric advantages of ART through better target coverage and Organs at Risk (OARs) sparing, with subsequent benefits on decreased toxicity and improved clinical outcome, specifically local control of the disease. ART replanning is a sustainable strategy for minimizing toxicity by improving normal tissue sparing. Furthermore, it enhances target volume coverage by correctly determining the specific amount of dose to be delivered to the tumor. In conclusion, this review confirms that ART benefits dosimetric, clinical/therapeutic, and toxicity outcomes.

Abstract Aim: Micro-invasive therapeutic approaches in endodontics differentiate between different modified types of access cavities: occlusal via a smaller occlusal opening (15 ° access angle), medial (via the caries defect) for premolars and molars (30 ° access angle) and cervical with wedge-shaped defects or root caries on anterior teeth and single-rooted premolars (45 ° access angle). Therefore, the aim of this work was (i) to create an in-vitro model for the clinical simulation of these three different modified access types, (ii) to assess the biomechanics of the instrumentation and (iii) to measure the volumetric substance loss of four different preparation systems. Material and Method: Simulated S-shaped root canals with a high degree of obliteration (ISO 10) in acrylic polymer bodies with canal entrance angles of 15 °, 30 ° and 45 ° were shaped with NaOCl (3%) irrigation under clinical simulation at body temperature (37 ° C) in randomized blinded sequences (n = 7) according to manufacturer's instructions: 1. Conventional geometry, not heat treated, up to 35 / .04 (F360, Komet) 2. Conventional geometry, heat-treated, spark-eroded up to 40 / .04 (Hyflex EDM, Coltene Hyflex) 3. Spiral geometry, heat treated, up to 36 / .03 (TruNatomy, DentsplySirona) 4. Distinctive spiral geometry, heat-treated (XP-Endo Shaper, FKG) The vectorization (AutoCAD) of the root canals was performed before and after preparation in the apical, middle and coronal third of the root canal. The volumetric loss of substance in cubic millimeters was recorded and statistically evaluated using an independent two-sided t-test. Clinical demonstrations include three cases of micro-invasive access cavities as final proof of principle of fast and safe root canal treatment. Results The total loss of volume at 15 ° entry angles is significantly lowest with TruNatomy and XP Endo. With an access angle of 30 °, the total loss remains low and increases with F360 and Hyflex .. At a 45 ° access angle, the group differences remain: TruNatomy (6.5 mm3) and XP Endo (6.4 mm3) versus F360 (8.3 mm3) and Hyflex (8.4 mm3). This difference in loss of simulated root dentin is highly significant. Conclusions Conventional instruments achieve optimal shape of apical third of root canals at all entrance angles only with higher substance loss in coronal and middle thirds . In contrast, the spiral instrument geometry contributes to dentin protection and supports the concept of minimally invasive endodontics for lifelong tooth preservation as shown in four clinical cases.

Financial capacity instruments are psychometric tools designed to evaluate individual decisional capacity based on financial decisions. As tests are complex and need special conditions for administration and evaluation, it is difficult to use them in daily geriatric clinics. Our scoping review objective was to evaluate existing financial capacity instruments from the perspective of simplicity and portability. We evaluated one English speaking knowledge database (Medline) using a dedicated MeSH terminology. The review yielded one independent instrument, The Semi-Structured Clinical Interview for Financial Capacity, that can be easy adapted for every-day clinical use. It is simple to understand and perform and do not need trained personnel for administration. It can be finalized in 15 minutes. Initially validated on 261 subjects (with different forms of cognitive impairment), it showed good accuracy and precision mainly in subjects with cognitive impairment. The test is less apt to detect early or fluctuating cognitive impairment. Simplicity, the main advantage of the test, allows gamification fact that increases portability. Familiar images (coins, money) that are used for performing simple tasks does not need complex translation and adaptation. In form of a game, the test is suitable for serial administration, increasing the chance for early capacity reduction detection. Results reflect a physician judgement related to the subjects’ capacity to understand and execute simple financial instructions and not financial proficiency scores. The main limitation of our review is that we investigated only one, English speaking, knowledge database. The scoping strategy generated a financial capacity instrument that can be used in geriatric clinics for early diagnostic of decisional capacity reduction. Further studies are needed to evaluate the reliability and validity of the test in conditions of serial administration and in populations having various financial experience.

We conducted a retrospective evaluation of the clinical outcomes and prognostic factors in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) treated with first-line androgen receptor signaling inhibitors (ARSI) in real-world clinical practice in Japan. Between 2012 and 2023, a total of 127 consecutive patients with nmCRPC received ARSI treatment. Overall survival (OS), metastatic-free survival (MFS), and prostate-specific antigen progression–free survival (PSA-PFS) from ARSI initiation were assessed using Kaplan–Meier methodology. Clinical factors associated with OS in nmCRPC were analyzed using the Cox proportional hazards model. Among the patients, 72, 26, 12, and 17 received enzalutamide (ENZ), abiraterone (ABI), apalutamide (APA), and darolutamide (DARO) as first-line therapy. The median OS and MFS for all patients were 79.0 and 42.0 months, respectively. Median PSA-PFS was 27.0, 20.0, 10.0, and 14.0 months for patients treated with ENZ, ABI, APA, and DARO, respectively (p = 0.33). Multivariate analysis revealed that a baseline PSA level ≥3.67 ng/ml at ARSI initiation was significantly associated with poorer OS (p = 0.002). ARSI demonstrated favorable efficacy in nmCRPC patients. There were no significant differences in clinical outcomes among different types of ARSI therapy for nmCRP. Elevated baseline PSA at ARSI initiation was significantly associated with poorer OS.