Introduction: Dengue is a mosquito transmitted arboviral infection. In dengue fever spontaneous bleeding in different parts of body occurs; but spontaneous bleeding into rectus muscle leading to haematoma formation is rare. Case Presentation: A 72-year-old hypertensive female presented with high grade intermittent fever with chills and rigors for last four days. She was diagnosed to have dengue fever (NS1Ag -Reactive) on the day before admission. At admission, on examination she was found to be have dehydration. Immediately she was put on IV fluids, antiemetics and other supportive therapy. At admission she had low platelets, low haemoglobin, total leucocyte counts, with raised liver enzymes. On day 3 of illness, she had significant drop of haematocrit with low blood pressure and subsequently she managed with packed red blood cell (PRBC) transfusion. But on 9th day of illness, she has severe right iliac fossa pain mimicking acute appendicitis. CECT of abdomen showed soft tissue lesion in right lower abdomen (Inflammatory/ hematoma along rectus sheath) which was managed conservatively as per surgical opinion. 10 days past discharge she had no pain in right iliac fossa and size of hematoma was significantly reduced. Discussion: In dengue fever, hematoma can be formed any vulnerable part in the but there are only a few cases reported to be having rectus sheath hematoma. Rectus sheath hematoma (RSH) has been mistaken for many acute abdominal diseases like- acute appendicitis. Our case mimicked acute appendicitis and managed conservatively with IV fluids, analgesics, Blood transfusion as it fits into RSH type II. Conclusion: It is important to be vigilant in the patients who presents with abdominal pain in severe dengue cases. Prompt imaging in relevant areas could make the diagnosis and father treatment possible.

Background: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and the quality of life. Methods: Our study included 59 patients with AMI and preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 hours of chest pain onset from aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACE) were evaluated at six months follow-up. Results: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p=0.038; OR 3.438; 95%CI: 1.275-9.265; p=0.015). ROC analysis identifies the Gal-3 plasma concentration from aortic root as a better predictor of MACE or death (cut-off >10.86 ng/ml; AUC 0.858; 95%CI: 0.744-0.973; p<0.001) than Gal-3 plasma concentration from femoral/radial artery (cut-off >10.18 ng/ml; AUC 0.742; 95%CI: 0.596-0.888; p=0.006). Conclusion: The Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 hours after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

We validated a new noninvasive tool (B4C) to assess intracranial pressure waveform (ICPW) morphology in a set of neurocritical patients, correlating the data with ICPW obtained from invasive catheter monitoring. Materials and Methods: Patients undergoing invasive intracranial pressure (ICP) monitoring were consecutively evaluated using the B4C sensor. Ultrasound-guided manual internal jugular vein (IJV) compression was performed to elevate ICP from the baseline. ICP values, amplitudes, and time intervals (P2/P1 ratio and time-to-peak [TTP]) between the ICP and B4C waveform peaks were analyzed. Results: Among 41 patients, the main causes for ICP monitoring included traumatic brain injury, subarachnoid hemorrhage, and stroke. Bland-Altman’s plot indicated agreement between the ICPW parameters obtained using both techniques. The strongest Pearson’s correlation for P2/P1 and TTP was observed among patients with no cranial damage (r = 0.72 and 0.85, respectively) in detriment of those who have undergone craniotomies or craniectomies. P2/P1 values of 1 were equivalent between the two techniques (area under the receiver operator curve [AUROC], 0.9) whereas B4C cut-off 1.2 was predictive of intracranial hypertension (AUROC 0.9, p < 000.1 for ICP > 20 mmHg). Conclusion: B4C provided biometric amplitude ratios correlated with ICPW variation morphology and is useful for noninvasive critical care monitoring.

We aimed to reveal the disease burden of aphasia after acute ischemic stroke (AIS) at the national level and investigate the impact of aphasia on tertiary care resources and patient outcomes. The local database from the Cluj-Napoca Emergency County Hospital (CNECH), the second largest stroke center in Romania was used to export demographics, baseline clinical and laboratory data, inpatient length of stay (LOS), NIH Stroke Scale (NIHSS), and discharge modified Rankin Scale (mRS) score data for all AIS patients admitted during March 2019. Of 92 patients included in the study, 30 (32.6 %) had aphasia on admission. In a marginally significant unadjusted hierarchical multiple regression model, individuals with aphasia had a LOS of 1.86 days longer than stroke survivors without aphasia. In an adjusted version of the model, the NIHSS score at baseline was a significant predictor for LOS. In addition, the presence of aphasia was associated with a 1.49 increase in the mean mRS score. Aphasia was a marginally significant predictor for increased LOS. Presence of aphasia was more likely to produce a poor functional outcome. Considering an estimated impact of approximately EUR 3 million on direct medical expenditure annually, future policymaking efforts should improve prevention of stroke and improved access to post-stroke aphasia care in Romania.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To contain the virus, numerous preventive measures have been taken including isolation of patients, careful infection control, social distancing, and taking vaccine. So far, new confirmed and death cases are still increasing. SARS-CoV-2 invades cells by using the angiotensin converting enzyme 2 (ACE2). ACE2 is an essential enzyme of the renin-angiotensin system (RAS) which converts angiotensin II (Ang II) to angiotensin (1-7). ACE2 is expressed in different organs, including lung, heart, and kidney. A high number of COVID-19 patients developed kidney injury has been reported. Renal impairment and acute injury are associated with mortality of COVID-19, which is 14-16 times higher than other general patients. Acute Kidney Injury has been occured in 2.9 up to 43% of intensive care unit patients. The increasing evidence show that the components of RAS can activate the complement cascade, and cytokines production. Kidney injury caused by SARS-CoV-2 is related mainly to systemic and local inflammation. Moreover, the uncontrolled immune responses mediated by SARS-CoV-2 including hypercytokinaemia, secondary hemophagocytic lymphohistiocytosis, antibody dependent enhancement, complement system, and phagocytic cells activation can contribute in the virus pathogenesis leading to associated renal dysfunction. However, the role and crosstalk between of RAS components and immune response in mediating kidney injury remain undefined. In this review, we focus on the recent studies to provide the pathogenesis of SARS-CoV-2 interacting with RAS and immune responses to mediate kidney injury.

Background: Morphological alterations in intracranial pressure pulse waveform (ICPPW) secondary to intracranial hypertension (ICP >20 mmHg) and reduction in intracranial compliance (ICC) are well known indicators of neurological severity. To date, no studies have documented the ICPPW modifications after intracranial hypertension resolution with decompressive craniectomy (DC). The present study aimed to assess the morphological alterations in ICPPW among neurocritical care patients with and without DC, by comparing the variations of ICPPW features according to elevations in mean ICP values. Methods: Patients requiring ICP monitoring because of severe traumatic or spontaneous conditions were included. Mean ICP values were compared with ICPPW features (P2/P1 ratio, TTP and pulse amplitude). Elevation in ICP was produced by means of ultrasound-guided manual internal jugular veins compression. Results were distributed for three groups: intact skull (exclusive burr hole for ICP monitoring), craniotomy/large fractures (group 2) or DC (group 3). Results: 57 patients were analyzed. 21 (36%) presented no skull defects, whereas 15 (26%) had DC. ICP was not significantly different between groups: ±13.59 for intact and ±17.66 mmHg for DC, with ICP induced elevation also similar between groups (p= 0.56). Significant elevation was observed for P2/P1 ratio for groups 1 and 2, whereas reduction was observed in group 3 (elevation of ±0.09 for groups 1 and 2, whereas reduction of 0.03 for group 3, p=0.01). Conclusion: In the present study, intracranial pressure pulse waveform analysis indicated that intracranial compliance was significantly more impaired among decompressive craniectomy patients, although ICPPW indicated DC to be protective for further influences of ICP elevations over the brain. Analysis of ICPPW seems to be an alternative to real time ICC assessment.

Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA. Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF). The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients - obs-AMI and MINOCA - NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI, a larger LVEDV and a lower LVEF compared to normoglycemic ones. Conversely, MINOCA patients showed similar myocardial damage, irrespective of glycemia. Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

Aim: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in hepatopancreaticobiliary (HPB) surgeries. Material and Methods: All the HPB surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and fisher t test wherever approptiate and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant. Results: We performed 195 HPB surgeries between April 2018 to March 2020, Which included 114 biliary surgeries, 57 liver surgeries and 23 pancreas surgeries. 10 patients developed Acute Kidney Injuries. (AKI) On Univariate analysis AKI was associated with open surgeries, intra operative hypotension and liver surgeries, higher ASA grade, increase operative time, more blood products used, higher CDC grade of surgery and more hospital stay before diagnosis of AKI. However on multivariate analysis only higher ASA score independently predicted Acute Kidney Injury. (p=0.003, odds ratio 15.659, 95% confidence interval 2.54-93.36). AKI was also significantly associated with mortality. (p <0.0001). Conclusion: Pre operative higher ASA grade independently predicted post operative acute kidney injury. Post operative AKI is significantly associated with mortality.

Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.

The anti-inflammatory effect of ginsenoside Rh2 (GRh2) is one of the most important ginsenosides. The purpose of this study is to identify the anti-inflammatory and antioxidant effects of GRh2 after LPS challenge lung injury animal model. GRh2 reduced LPS-induced NO, TNF-α, IL-1, IL-4, IL-6 and IL-10 productions in lung tissues. GRh2 treatment decreased the histological alterations in the lung tissues and BALF protein content and total cells number also diminished in LPS-induced lung injury mice. Moreover, GRh2 blocked iNOS, COX-2, the phosphorylation of IκB-α, ERK, JNK, p38, Raf-1 and MEK protein expression which is corresponded to the growth of HO-1, Nrf-2, catalase, SOD and GPx expressions in LPS-induce lung injury. An experimental study has suggested that GRh2 has provided with anti-inflammatory effects in vivo, and its potential therapeutic efficacy in major anterior segment lung diseases.

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

Background A decline in cardiovascular hospitalizations was observed during the initial phases of the COVID-19 pandemic. We examine the continued effect of the pandemic on cardiovascular hospitalizations and the associated mortality rates during the first year of the pandemic in Israel. Methods We conduct a retrospective cohort study using the data of Clalit Health Services, the largest healthcare organization in Israel. We divide the Corona year into six periods (three lockdowns and three post-lockdowns) and compare the incidence rates of cardiovascular hospitalizations and their 30-day mortality during each period to the previous three years. Results The number of non-STEMI hospitalizations during the first year of the pandemic was 13.7% lower than the average of the previous three years (95% CI 11%-17%); STEMI hospitalizations were 15.7% lower (95% CI 13%-19%); and CHF hospitalizations were 23.9% lower (95%, CI 21%-27%). No significant differences in 30-day mortality rates were observed for AMI patients during most of the periods, whereas the annual 30-day all-cause mortality rate of CHF was 23% higher. Conclusions Hospitalizations for AMI and CHF were significantly lower during the first year of the pandemic relative to 2017–9. Mortality rates were higher in the case of CHF patients but not in the case of AMI patients, possibly due a change in the clinical acuity of patients arriving at the hospitals. We conclude that targeted public health messaging should be implemented, together with proactive monitoring in order to identify residual disability in patients that may have received non-optimal treatment during the pandemic.

Abstract The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA), which is a molecular target for all-transretinoic acid (ATRA) and arsenic trioxide (ATO). Therapies with ATRA plus ATO have excellent outcomes in terms of complete remission rate, overall survival, and achievement of a deep and durable molecular response with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of unique toxicities, such as hepatic toxicity, QTc (QT interval corrected) prolongation, neurotoxicity, and differentiation syndrome. Hematologists treating patients with acute promyelocytic leukemia should be aware of possible early-complications of the ATRA plus ATO regimen and aim to balance treatment-related adverse events and efficacy. Careful follow-up of the patient’s clinical course is essential to identify and treat each complication. This study focused on treatment-related complications during induction and consolidations in patients with APL who received ATRA plus ATO. We retrospectively analyzed 26 adult patients diagnosed with APL between 2019 and 2022 at our center to identify the incidence rate, severity and time of onset of short-term non-hematologic adverse events relative to the initiation of the ATRA and ATO regimen. Additionally, we review the existing literature regarding the toxic side effects of ATO in APL and discuss how its most frequent toxicities should be managed. The median follow-up of our patients was 21.5 months (range, 1-48 months) and the most common adverse events were hepatic toxicity (69.2%), infections (46.1%), differentiation syndrome(23%) and QT prolongation (11.5%). All patients experienced at least one adverse event and grade 3 and 4 toxicities occurred in 57.6 % patients; these generally consisted of liver enzyme elevations, QTc prolongation, but also some rare manifestations such as musculoskeletal pain syndrome (1 patient) and ATO-related pancreatitis (1 patient). Most patients developed side-effects during induction. This is the first study about Romanian patients diagnosed with APL. Our results suggest that all treatment-related adverse events, except for differentiation syndrome are manageable, self-limiting and reversible. All patients, except for two (one died during induction and one died during consolidation), were able to complete the treatment consolidation with ATO and ATRA.

AML is a highly aggressive and heterogeneous form of hematological cancer. Proteomics-based stratification of patients into more refined subgroups may contribute to a more precise characterization of the patient-derived AML cells. Here, we reanalyzed liquid chromatography-tandem mass spectrometry (LC-MS/MS) generated proteomic and phosphoproteomic data from 26 chemoresistant/relapse (RELAPSE) and 15 relapse-free (REL_FREE) AML patients. We considered not only the RELAPSE and REL_FREE characteristics but also integrated the French-American-British (FAB) classification, along with considering the presence of nucleophosmin 1 (NPM1) mutation and cytogenetically normal AML. We found a significant number of differentially enriched proteins (911) and phosphoproteins (257) between the various FAB subtypes in RELAPSE patients. Patients with the myeloblastic M1/M2 subtype showed higher levels of RNA processing-related routes and lower levels of signaling related to terms like translation and degranulation, when compared to the M4/M5 subtype. Moreover, we found that high abundance of proteins associated to mitochondrial translation and oxidative phosphorylation, particularly observed in the RELAPSE M4/M5 NPM1 mutated subgroup, distinguishes relapsing from non-relapsing AML patient cells with the FAB subtype M4/M5. Thus, the discovery of subtype-specific biomarkers through proteomic profiling may complement the existing classification system for AML and potentially aid in selecting personalized treatment strategies for individual patients.

Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

Urinary tract infections (UTIs) are very frequent in women and can be caused by a range of pathogens. High recurrence rates and increasing antibiotic resistance of uropathogens make UTIs a severe public health problem. d-mannose is a monosaccharide that can inhibit bacterial adhesion to the urothelium after oral intake. Several clinical studies have shown the efficacy of d-mannose in the prevention of recurrent UTI; these also provided limited evidence for the efficacy of d-mannose in acute therapy. A recent prospective, non-interventional study in female patients with acute cystitis reported good success rates for treatment with d-mannose. Here we present data from a post-hoc analysis of this study to compare the cure rate of d-mannose monotherapy with that of antibiotics. The results show that d-mannose is a promising alternative to antibiotics in the treatment of acute uncomplicated UTIs in women.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

Coronavirus infection disease -2019 (COVID-19) was a global pandemic with high mortality and morbidity, that lead to an increased health burned all over the world. Although the virus affects mostly pulmonary tract, cardiovascular implications were often among COVID-19 positive patients, and are predictive for poor outcomes. Increased values of myocardial biomarkers such as Troponin I or NT-proBNP were proven to be risk factors for respiratory failure (26). Although the risk of acute coronary syndromes (ACS) was greater in acute-phase of COVID-19, there were lower rates of hospitalization for ACS, due to patient’s hesitation for presenting at the hospital (22). Hospitalized ACS patients with COVID-19 infection, had a prolonged symptom-to-first medical contact time, and longer door-to-balloon time. The mechanisms of myocardial injurie in COVID -19 patients are not still not clear, most often is incriminated: the down-regulation of ACE2 inhibitors, endothelial disfunction, pro-coagulant status, increased levels of pro-inflammatory cytokines. The aim of this paper is to evaluate the long-term outcomes of COVID-19 survivors that presented an acute myocardial infarction by reviewing existing data.

Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor, is the cornerstone of post-percutaneous coronary intervention treatment to prevent stent thrombosis and reduce the risk of adverse cardiovascular events. The selection of an optimal DAPT regimen, considering the interplay of various antiplatelet agents, patient profiles, and procedural characteristics, remains an evolving challenge. Traditionally, a standard duration of 12 months has been recommended for DAPT in most patients. While contemporary guidelines provide general frameworks, DAPT modulation with longer or shorter treatment courses followed by aspirin or P2Y12 inhibitor monotherapy are evolving towards an individualized strategy to optimize the balance between efficacy and safety. This review comprehensively examines the current landscape of DAPT strategies after coronary stenting, with a focus on emerging evidence for treatment individualization.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic method. The multitude of different etiological factors, the diversity of the clinical picture and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated diseases that in their natural course can lead to myocardial involvement, but also the iatrogenic cause of myocarditis due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, changes in ECG and echocardiography has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive diagnostic gold standard for diagnosis and clinical follow-up of thses patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening patients with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high.

Over the last 20 years, there has been a significant increase in the number of unexplained physiological events (UPEs) reported by pilots of fighter jets across different fleets. The UPEs have resulted in grounding some types of aircraft, loss of airplanes, and even loss of life. Despite considerable research, no single agreed-upon root cause has been found that explains UPEs, and therefore no reliable corrective actions exist. The purpose of this review was to analyze the literature related to other industries in which artificial hyperoxic gas mixes are employed and similar adverse reports have been reported. Based on analysis of the literature, it is hypothesized that UPEs are caused by unlimited delivery of high-dose oxygen in excess of officially approved oxygen schedules in the presence of inadequate airflow rates, at a time when the positive pressure breathing feature of their oxygen regulator system is not used. During flight maneuvers such as climbs, turns, and descents, pulmonary vital capacity is impaired by G-maneuvers and oxygen- and G-induced atelectasis. At the same time, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation. These factors combine to produce hypercarbia, respiratory acidosis, acute respiratory distress syndrome, CO₂ narcosis, and coma. In fact, reports from field data related to incidents in F-18S/H, showing that emergency oxygen did not correct the hypoxia-like symptoms including long-lasting periods of incapacitation and prolonged headaches, lend support to this hypothesis.

Introduction: Post-COVID-19 syndrome (PCS) is a multisystemic disorder marked by impaired physical performance as one lead symptom. Since it has been suggested that endurance training as part of medical rehabilitation may be effective to improve physical performance capacity in PCS, this study aimed to compare different modes of aerobic endurance training. Methods: Hundred-ten PCS patients (49.3±11.8 years, 38% women, time after infection=260.2±127.5 days) underwent detailed clinical screening including symptom-limited cardiopulmonary exercise testing at admission and after 4-6 weeks of inpatient medical rehabilitation. Questionnaires were used to assess disease perception. Patients performed controlled isocaloric cycle ergometer training (3-5 sessions/week, 18 min) as either continuous training (CT) at 50% of maximal workload or as interval training (IT, load=60%, relief=30%). Outcomes of PCS patients were compared to coronary artery disease patients (CAD, n=96) to evaluate overall training effectiveness. Results: Training participation was comparable between both groups with no indication of training-specific exercise-induced fatigue. Overall, PCS patients improved significantly by a mean of 6.8±12.1% for W at VT1, 3.1±10.0% for VO2 at VT1, 5.5±14.7% for O2-pulse at VT1, 7.5±15.0% for W at VO2peak, 2.7±11.0% for VO2peak and 4.6±12.4% for O2-pulse at VO2peak (all p<0.05) with no significant differences between groups (p>0.05). Both groups showed reduced levels of fatigue, anxiety and depression as well as improved quality of life and wellbeing (all p<0.05). Compared to guideline-based cardiac rehabilitation, PCS patients showed a similar improvement in workload and oxygen uptake compared to CAD patients. Conclusion: PCS patients benefit from aerobic endurance training, performed as moderate continuous or interval training as part of a medical rehabilitation program in terms of improved physical exercise capacity and disease perception. Results for PCS patients are comparable to guideline-based rehabilitation of CAD patients. Clinical Trial: NCT06016192

Objective: To explore the application effect of Atropine injection combined with nursing intervention on the interventional treatment of PATENTS with ST-segment elevation myocardial infarction. Methods: A total of 60 patients with ST-segment elevation myocardial infarction treated in our hospital from January 2022 to January 2023 were selected as the research objects. According to different nursing methods, they were divided into conventional group (n = 30) and systematic group (n = 30), both groups were treated with percutaneous coronary intervention (PCI). The conventional group received routine nursing before and after operation. On the basis of routine nursing, systematic nursing cooperation was given in the system group. The time of opening infarct vessels, the incidence of total adverse reactions during interventional treatment, mortality, success rate of treatment, improvement of cardiac function and length of hospital stay were compared between the two groups. Results: The time of opening infarct vessel in system group was significantly better than that in routine group (P < 0.05). The total adverse reaction rate in system group was significantly lower than that in routine group (P < 0.05); The mortality of routine group was significantly higher than that of system group (P < 0.05). The success rate of system group was significantly higher than that of routine group (P < 0.05); The number of patients with improved cardiac function and length of hospital stay in system group were significantly better than those in routine group (P < 0.05). Conclusion: Good intraoperative cooperation and nursing is an important guarantee for patients with ST-segment elevation myocardial infarction, which can effectively reduce the occurrence of adverse reactions during interventional treatment, improve the success rate of treatment, and reduce the death of patients during interventional treatment.

United Nations Scientific Committee on the Effects of 2006 report was the first document released by an abandoned the classical paradigm that ionizing suppressive, considering the idea that at low doses enhances the appearance of antiinflammatory biomarkers [UNSCEAR 2006]. It considers energetic an immune modulation agent due to the multitude the innate immune system, depending on various age, health status, co-morbidities, genetic background, co-stressors [Lumniczky et al.]. Natural background radiation is the most hazardous public health, followed by medical imaging as a close Naturally occurring radionuclides attach to particulate ionizing radiation after inhalation and deposition in the in this article that exposure to particle radioactivity of inflammation. With that purpose, we have done an on common anti-inflammatory biomarkers between cases on COVID-19 elderly patients, and those found low-intensity natural ionizing radiation in locations with hypothesize that radioactivity increases biomarkers of strategy involved the use of databases from PubMed, (e.g., dose response, hormesis, J-shaped, NLRP3 LNT model, etc.). Extrapolating these effects to artificial ionizing radiation drawn conclusions on the over use of X-ray computed images in elderly ICU admitted patients with pulmonary oxygen species (ROS) generation by this action seems inflammation of leucine-rich protein 3 (NLRP3) inflammasome, waking up an over cytokine production.

Background and Objectives: Acute compartment syndrome (ACS) is an emergency condition of the lower limb in which prophylactic fasciotomy is required to prevent complications. A negative pressure wound therapy (NPWT) used to the treatment of fasciotomy wounds provide beneficial clinical results. This study aimed to exchange the authors’ experience of using the NPWT installation system on the lower limb wounds after fasciotomy in ACS. Materials and Methods: This is a retrospective study enrolled consecutive patients with ACS, who underwent fasciotomy and was treated with the NPWT installation system at Department of Vascular Surgery, Provincial Hospital in Kielce from April 2016 to July 2017. Results: The study enrolled 15 patients with a diagnosis of ACS (87% men, mean age 65 years old). An open four-compartment fasciotomy (87%) or two-compartment fasciotomy (13%) was performed. The NPWT was applied on the first day after fasciotomy in 87% of patients. Therapy was initiated by the negative pressure of 125 mm Hg, which maintained at this level until the therapy was finalized. In 80% of patients, the vacuum-assisted wound closure (VAC) dressing changes were performed every 3 days. The first approximation of fasciotomy wounds margins occurred on the 4th day after surgery among 67% of individuals. The average time of using VAC on fasciotomy wounds was 9 days. The average time to definitive closure edges of fasciotomy wounds was 12 days. The average time of hospital stay was 17 days. Conclusions: Our experience indicates the legitimacy of using NPWT in wound treatment after fasciotomy in ACS. The NPWT enables faster primary closure of wounds, reduces edema, as well as decreases hospitalization time.

Background: Citicoline, a medical food, lacks proven efficacy for ischemic stroke and has uncertainties around its harms. The continued prescription should be reevaluated given the more robust, high-quality Evidence against that medical food. This essay is based on a recent Cochrane review and uses only one all-cause mortality as the primary outcome. Therefore, the essay should be considered as something other than an updated Cochrane review but like a reflection based on Evidence-based Medicine and Philosophy of Science analysis. Question Research: Why citicoline (a medical food) should not be prescribed to treat people with acute ischemic stroke: The certainty of the Evidence.? Objective: Demonstrate from evidence-based medicine and philosophy of science perspective that citicoline should not be prescribed for acute ischemic stroke due to lack of efficacy and harm uncertainties. Search publications: We searched in PubMed and Cochrane Library from 2020 until 30 October 2023. We, furthermore, used engineering machines Bing and Google Scholar to detect additional papers. Additionally, we also reviewed reference lists of the retrieved publications and review articles and searched the websites of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). Selection criteria: We included systematic reviews, meta-analyses, randomized clinical trials, clinical guidelines focused on acute ischemic stroke and comparing citicoline versus placebo or no intervention. We excluded narrative reviews, observational studies and ongoing trials. Data collection and analysis: We identified only new randomized clinical trials and assessed the risk of bias in seven domains. The other eight trials were already included in the mentioned Cochrane review. The systematic reviews with or without meta-analyses were assessed using McMaster University guidelines. We estimated risk ratios (RRs) for that outcome. We measured statistical heterogeneity using the I² statistic. We conducted our analyses using the fixed effect model. We did not use the GRADE approach due to what is shown in a Cochrane review published in 2020 by Martí-Carvajal et al. We used the RevMan 5.4 software from Cochrane Collaboration to conduct the forest plot. We used a Trial Sequential Analysis with Copenhagen Trial Unit Software. We estimated a Bayes factor from the relative risk and 95% confidence interval. Results: We identified only one new RCT (N = 99) reported mortality data and three clinical guidelines. We conducted a new meta-analysis with nine trials (N = 4461) having a high risk of bias and showing little to no difference in mortality between citicoline and placebo (17.1% vs 18.4%; RR 0.94, 95% CI 0.82 to 1.06; I2 = 0%). The Bayes factor was 0.7, indicating weak Evidence for the null over the alternative hypothesis. Trial sequential analysis suggested sufficiency of Evidence for mortality. No guidelines recommend citicoline. Conclusions: This essay reassessed citicoline for acute ischemic stroke after the 2020 Cochrane review. Adding a new RCT further supported the lack of mortality benefit with citicoline. The overall evidence quality could be better. Analyses using evidence-based medicine and philosophy of science approaches do not support prescribing citicoline due to a lack of efficacy substantiation and potential harms.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents AKI can be prevented effectively through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans) longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, in particular arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Methotrexate is an antimetabolic agent with proliferative and immunosuppressive activity. It has been demonstrated to be an effective treatment for acute lymphoblastic leukemia (ALL) in children. However, there is evidence of an association between methotrexate and toxicity risks, which influences the personalization of treatment, particularly in the case of childhood ALL. This article presents the development and implementation of an algorithm based on artificial neural networks to detect methotrexate toxicity in pediatric patients with acute lymphoblastic leukemia. The algorithm utilizes historical clinical and laboratory data, with an effectiveness of 99% in the tests performed with the patients dataset. The use of neural networks in medicine is often linked to disease diagnosis systems. However, neural networks are not only capable of recognizing examples, but also hold very important information. For this reason, one of the main areas of application of neural networks is the interpretation of medical data. In this article we diagnose with the application of neural networks in medicine with a concrete example: Detecting Methotrexate in Pediatric Patient in its early stages.

The Kounis syndrome (KS) is an acute coronary syndrome triggered by allergic or hypersensitiv-ity reactions. Incidence rates vary, with studies reporting 19.4 per 100.000 among all admissions and 3.4% among allergy patients. This review explores the expanding understanding of KS, en-compassing various manifestations, and focusing on both clinical data and forensic findings useful in performing the diagnosis. The pathophysiology of this syndrome involves a complex in-terplay between allergic reactions and the cardiovascular system. Mast cell activation, histamine release, leukotrienes, cytokines, and platelet activation can contribute to the coronary events. A classification system with three types (Allergic Angina, Allergic Myocardial Infarction, Allergic Stent Thrombosis) aids in categorizing presentations. The diagnosis of KS relies on clinical presentation, laboratory findings and imaging. Post mortem assessment of KS is based on the in-tegration of circumstantial data, autopsy and histological findings. Biochemical and immuno-histochemical analyses also contribute to post-mortem diagnosis. In conclusion, a combined, multidisciplinary approach, should be gained to ease diagnostic pro-cess which is crucial for forensic practitioners in confirming KS occurrence.

The ubiquitous peptide endothelin is currently under investigation as a modulatory factor of autonomic responses to acute emotional stress. Baseline plasma levels of endothelin alter blood pressor responses, but it remains unclear whether autonomic activity and arrhythmogenesis are affected. We recorded sympathetic and vagal indices (derived from heart rate variability analysis), rhythm disturbances, voluntary motion, and blood pressure after acute emotional stress in conscious rats with implanted telemetry devices. Two strains were compared, namely wild-type and ETB-deficient rats, the latter displaying elevated plasma endothelin. No differences in heart rate or blood pressure were evident, but sympathetic responses were blunted in ETB-deficient rats, contrasting prompt activation in wild-type rats. Vagal withdrawal was observed in both strains at the onset of stress, but vagal activity was subsequently restored in ETB-deficient rats, accompanied by low voluntary motion during recovery. Reflecting such distinct autonomic patterns, frequent premature ventricular contractions were recorded in wild-type rats, as opposed to sinus pauses in ETB-deficient rats. Thus, chronically elevated plasma endothelin levels blunt autonomic responses to acute emotional stress, resulting in vagal dominance and bradyarrhythmias. Our findings provide further insights into the pathophysiology of stress-induced tachyarrhythmias and syncope.

The thyroid-heart relationship has a long and articulated history of its own, a history that en-compasses physiological and pathophysiological knowledge, the latter particularly in the context of cardiac diseases such as heart failure, arrhythmias and ischaemic heart disease. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, being an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addi-tion, in the last few years, several studies have been carried out on the prognostic impact of al-terations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and therefore with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart-thyroid relation-ship.

It has been previously shown that aldehyde dehydrogenase (ALDH) family member ALDH1A1 has a significant association with acute myeloid leukemia (AML) patient risk group classification, and that AML cells lacking ALDH1A1 expression can be readily killed by chemotherapy. In the past, however, a redundancy between the activities of subgroup members of the ALDH family has hampered conclusive evidence for addressing the role of specific ALDH genes. We here describe the bioinformatics evaluation of all nineteen member genes of the ALDH family as prospective actionable targets for the development of methods aimed to improve AML treatment. We implicate ALDH1A1 in the development of recurrent AML, and we show that from the nineteen members of the ALDH family, ALDH1A1 and ALDH2 have the strongest association with AML patient risk group classification. Furthermore, we discover that the sum of the expression values for RNA from the genes ALDH1A1 and ALDH2 has a stronger association with AML patient risk group classification and survival than either one gene alone. In conclusion, we identify ALDH1A1 and ALDH2 as prospective actionable targets for the treatment of AML in high risk patients. Substances that inhibit both enzymatic activities can constitute potentially effective pharmaceutics.

Measuring the non-pathogenic Torque Teno Virus (TTV) load allows assessing the net immunosuppressive state after kidney transplantation (KTx). Currently, it is not known how exposure to maintenance immunosuppression affects TTV load. We hypothesized that TTV load is associated with the exposure to mycophenolic acid (MPA) and tacrolimus. We performed a prospective study including 54 consecutive KTx. Blood TTV load was measured by an in-house PCR at months 1 and 3. Together with doses and trough blood levels of tacrolimus and MPA, we calculate the coefficient of variability (CV), time in therapeutic range (TTR) and concentration/dose ratio (C/D) of tacrolimus, and the MPA-area under the curve (AUC-MPA) at the third month. TTV load at the first and third month discriminated those patients at risk of developing opportunistic infections between months 1 and 3 (AUC-ROC 0.723, 95%CI 0.559-0.905, p = 0.023) and between months 3 to 6 (AUC-ROC 0.778, 95%CI 0.599-0.957, p = 0.028), respectively, but not those at risk of acute rejection. TTV load did not relate to mean tacrolimus blood level, CV, TTR, C/D and AUC-MPA. To conclude, although TTV is a useful marker of net immunosuppressive status after KTx, it is not related to exposure to maintenance immunosuppression.

Porphyrias are human metabolic diseases characterized by different modes of inheritance and clinical manifestations and caused by deficiency of enzymes of the heme biosynthetic pathway. The forms of porphyria are characterized by elevated levels of δ-aminolevulinic acid and porphobilinogen. Acute hepatic porphyrias are a subgroup of porphyrias characterized by the appearance of neurovisceral attacks with or without cutaneous signs. Acute hepatic porphyrias include four diseases: acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and hereditary δ-aminolevulinic acid dehydratase deficiency. These enzymatic deficiencies cause a harmful accumulation of porphyrins in the liver and bone marrow that trigger a wide range of signs and symptoms. Patients suffering from different forms of acute hepatic porphyria present a high risk of liver cancer, precisely hepatocellular carcinoma and cholangiocarcinoma, determined by the activity of the disease even though an exact mechanism of carcinogenesis has not been recognized yet. Here, we present the clinical case of a 72 year old woman who, approximately 29 years after the diagnosis of acute intermittent porphyria, presented with intrahepatic cholangiocarcinoma with histological diagnosis of adenocarcinoma starting from the biliary-pancreatic ducts, which was diagnosed during the clinical and anatomopathological evaluation of a pathological fracture of the femur.

Infectious disease is the leading cause of mortality in children under five. This study has investigated environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM study in Matiari, Pakistan. Publicly available map data was used to compile coordinates of healthcare facilities. A Pearson correlation coefficient (r) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found participants living closer to secondary hospitals had lower prevalence of ARI (r=0.154, p&lt;0.010) and diarrhea (r=0.228, p&lt;0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI (r=0.185, p&lt;0.002) and diarrhea (r=0.223, p&lt;0.001) compared to those living near primary facilities. Our random forest model showed distance to have high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.

NPM interaction with tumor suppressor p53 is a part of a complex interaction network and considerably affects cellular stress response. An impact of characteristic AML-associated NPM mutations on interaction with p53 has not been investigated yet, although consequences of NPMmut-induced p53 export to the cytoplasm are important for understanding of leukemogenic potential of these mutations. We investigated p53-NPM interaction in live HEK-293T cells by FLIM-FRET and in cell lysates by immunoprecipitation. Results were confirmed in leukemia cell lines. eGFP lifetime-photoconversion was used to follow redistribution dynamics of NPMmut and p53 in Selinexor-treated cells. We confirmed the p53-NPMwt interaction in intact cells and newly documented that this interaction is not compromised by the NPM mutation causing displacement of p53 to the cytoplasm. Importantly, the interaction was not abolished for non-oligomerizing NPM variants with truncated oligomerization domain, suggesting that oligomerization is not essential for interaction of NPM forms with p53. Inhibition of the nuclear exporter XPO1 by Selinexor caused expected nuclear relocalization of both NPMmut and p53. However, significantly different return rates of these proteins indicate nontrivial mechanism of p53 and NPMmut cellular trafficking. We suggest that the altered p53 regulation in cells expressing NPMmut offers a new target for AML therapy.

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo Rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the Rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with Rapamycin (10 ng/ml) for 1 hour before LPS. In contrast, Rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo Rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of Rapamycin treated DCs to WT recipients 24 hrs before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/ml) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

The association between the choice of general anesthetic agents and the risk of acute kidney injury (AKI) and long-term renal function after nephrectomy has not yet been evaluated. We reviewed 1087 cases of partial or radical nephrectomy. The incidence of postoperative AKI, new-onset chronic kidney disease (CKD) stage 3a and CKD upstaging were compared between different general anesthetic agent groups: propofol, sevoflurane, and desflurane. Four different propensity score analyses were performed to minimize confounding for each pair of comparison (propofol vs sevoflurane; propofol vs desflurane; sevoflurane vs desflurane; propofol vs volatile agents). Study outcomes were compared before and after matching. Kaplan-Meier survival curve analysis was performed to compare renal survival determined by the development of CKD stage 3a between groups up to 36 months after nephrectomy before and after matching. Propofol was associated with a lower incidence of AKI, CKD upstaging and a higher three-year renal survival after nephrectomy compared to sevoflurane or desflurane group after matching (AKI: propofol 23.2% vs. sevoflurane 39.5%, P=0.004, vs. desflurane 34.3%, P=0.031; CKD upstaging: propofol 27.2% vs. sevoflurane 58.4%, P<0.001, vs. desflurane 48.6%, P=0.017; Log-rank test propofol vs. sevoflurane P<0.001, vs. desflurane P=0.015). Propofol was also associated with a lower incidence of new-onset CKD after nephrectomy compared to sevoflurane after matching (P<0.001). However, there were no significant differences between sevoflurane and desflurane. In conclusion, propofol, compared to volatile agents, may be the reasonable choice of general anesthetic agent for nephrectomy to attenuate postoperative renal dysfunction. Randomized prospective trials are warranted to test this hypothesis.

Comprehensive geriatric assessment, defined as an interdisciplinary assessment and development of an overall plan of treatment and follow-up, has become a fundamental part of clinical geriatric care. Since the 1970s, the Veterans Administration has encouraged the development of geriatric evaluation and management programs. Evolution of geriatric evaluation and management has occurred over time and many VA medical centers have transferred inpatient geriatric evaluation programs to long-term care Community Living Centers (CLC) and outpatient settings. Availability of resources and trained personnel across the continuum of care as well as administrative facilitation of collaboration between care components are critical to the efficient utilization of geriatric services. Facilities may need to prioritize their resources and utilize the most effective and relevant elements of geriatric evaluation and management according to patient population needs, available space, resources, and institutional priorities.

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial if the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: 410 Patients were divided into two groups concerning the DHCA time less than 60 minutes and equal or longer than 60 minutes. (3) Results: Patients with longer DHCA time were significantly younger (p=0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA time (p&lt;0.001). Accordingly, cardiopulmonary bypass (p&lt;0.001), cross-clamping (p&lt;0.001) and DHCA times (p&lt;0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p&lt;0.001) and the rate of tracheotomy were significantly higher in these patients. 30-day mortality was satisfactory for both groups (p=0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow a successful performance of surgical treatment of AAAD under DHCA with duration of even longer than 60 minutes.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. AML with mutated Nucleophosmin1 (NPM1-mut) is the largest of the genetically defined groups, involving about 30% of adult AMLs and is currently recognized as a distinct entity in the actual AML classifications. NPM1-mut AML usually occurs in de novo AML and is associated predominantly with a normal karyotype and relatively favorable prognosis. However, NPM1-mut AMLs are genetically, transcriptionally, and phenotypically heterogeneous. Furthermore, NPM1-mut is a clinically heterogenous group. Recent studies have in part clarified the consistent heterogeneities of these AMLs and have strongly supported the need for an additional stratification aiming to improve the therapeutic response of the different subgroups of NPM1-mut AML patients.

The cork oak (Quercus suber L.), endemic essence of the Mediterranean Basin, is commonly used in traditional pharmacopoeia. The main objective of this work is to enhance the valorization of this plant species through the study of the anticandidosic activity of cork oak bark methalonic extracts in order to develop an efficient natural formulation for Candidiasis treatment.The anticandidosic activity of methanolic extracts of Q. suber bark stemming from decoction, maceration and Soxhlet methods of extraction in was tested on five different Candida albicans strains. Our results showed that all the tested extracts displayed an inhibitive activity, which varies according to the obtained extract and the tested strain. The best anticandidosic potential was observed with extracts obtained with Soxhlet method. The study of the acute toxicity showed that the lethal dose is 1150 mg/kg in mice, which remained moderately toxic according to Hodge and Sterner classification scale. Thus, this extract can be used in phytotherapy without danger in doses that are below 300 mg/kg of corporal weight. Based on these results, we can conclude that Cork oak bark extracts can be used to treat Candida albicans infections.

The COVID-19 pandemic has revealed many knowledge gaps with implications toward the speed and nature of our response to contain, assess and mitigate risk. The routine discharge of treated and untreated wastewater into rivers and coastal waters has placed SARS-CoV-2 viability in wastewater at the centre of an emerging hazard and potential risk to water industry workers and the public who come into contact with sewage-impacted water. Here we provide a review of the Severe Acute Respiratory Syndrome coronavirus primary literature that presents the evidence base pertaining to the key questions of whether the SARS-CoV-1 and SARS-CoV-2 is shed in stool and urine, is recoverable, and infectious in wastewater. We discuss the challenges posed by the current literature base and the extent to which the current evidence is fit for the purpose of informing robust human and environmental risk assessments.

The term “medical error” is quite often used to refer to any mistake committed in the provision of healthcare services which has caused harm to a patient. Objective: To analyze civil lawsuits involving medical errors in pediatrics by evaluating: 1) causal link; 2) type of medical error; 3) conviction of the court and its legal basis; 4) correlation between medical expert understanding and legal understanding. Materials and Method: Retrospective analysis of 60 pediatric forensic medical examinations carried out by a pediatric expert between April 2009 and February 2014 at the Institute of Medicine and Criminology of the State of São Paulo (IMESC). The expert’s reports were analyzed according to age, gender, type of forensic medical report (direct or indirect), conclusion of the expert’s report (causal link between the medical conduct and complaint or not), type of medical error (negligence, recklessness, malpractice), judgment in the first instance (if in accordance with the expert’s report or not), and basis of judgment as objective or subjective (type of law). Results: Most expert’s examinations (65%) were indirect (death). In 27 reports (45%), the expert’s conclusion determined that there was a causal link between medical care and the damage inflicted to a patient. Of the 27 reports with causal link, the judge was not in accordance with the expert’s report in one case, thus not considering medical error. The vast majority of sentences (55) were in accordance with the expert’s conclusion (91.6%). Subjective law was mostly used to support the judge’s ruling (61.70%), followed by objective law (23.30%). All lawsuits claimed moral damages (100%). In the statistical analysis of distribution of nominal variables (frequency), an excellent agreement (kappa= 0.86), with statistical significance, was verified between the expert’s report and the court ruling. Conclusion: Expert evidence supported 91.6% of the sentences and was considered to be highly valuable evidence. Expert evidence had a major impact on the legal proceedings and has proven statistically significant (p<0.005). Subjective law was used to assess medical error in all cases in which healthcare professionals were involved. Claims for moral damages was requested in all lawsuits, and was fully or partially granted in 100% of the cases.

Introduction: Otitis media with effusion (OME) is common in pediatric primary care consultations. Its etiology is multifactorial, although it has been proven that inflammation factors mediate and that immunity is in a phase of relative immaturity. The objective of this study was to assess the effects of the Traditional Mediterranean Diet (TMD) modulating inflammation and immunity in patients diagnosed with OME.

Background: Myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, is a rare disease entity characterized by the emergence of an extramedullary tumour which may be antecedent, coexisting or manifest secondarily to an ongoing malignancy of lymphoid origin. Owing to its low prevalence, scientific reports addressing this matter comprise mainly retrospective studies with a limited number of participants, rather low-quality research and only few case reports. Despite MS’s rarity, the need for enhancing diagnostic tools and refinement of therapeutic regimens is broadly recognised among physicians. Case summary: In this case series, we present the clinical histories of two patients diagnosed with MS. The former (Case 1) exhibited MS of the sternum alongside chronic myeloid leukemia (CML), while in case of the latter (Case 2) MS was the initial manifestation of a current acute myeloid leukemia (AML). Regardless of treatment institution comprising chemotherapy (CHTH) and radiotherapy (RT), the patient afflicted by CML did eventually pass due to cardiorespiratory insufficiency secondary to an infection, whereas the second one is in clinical remission up to this date, that is 16 months since MS had been diagnosed. Furthermore, a comprehensive analysis of previously reported cases was conducted which involves MS in patients with AML and CML. Conclusion: The objective of this report is to emphasize the heterogeneity among the clinical manifestations of MS, to underline the relevance of histopathological and molecular diagnostic tools in opting for the appropriate therapy and that, in spite of it occurring rather uncommonly, physicians should think of MS in presence of pathological masses in patients under risk of hematological malignancies.

Acute Oak Decline (AOD) is complex syndrome affecting Britain’s keystone native oak species, (Quercus robur L. and Q. petraea L. (Matt.) Liebl.), in some cases causing mortality within five years of symptom development. The most distinguishable symptom is weeping stem lesions, from which four species of bacteria have been isolated: Brenneria goodwinii, Gibbsiella quercinecans, Lonsdalea britannica and Rahnella victoriana. We do not yet know where else these bacteria exist, and little is known about the relationship of the wider oak leaf microbiome (phyllosphere) to acute oak decline. Here we investigate whether incidental evidence from a large oak genome re-sequencing dataset could be used to detect these bacteria in oak foliage, and whether bacterial incidence co-varied with AOD status or location. Oak leaves and buds were sampled from 421 trees at five sites in England. Whole genomic DNA from these samples was shot-gun sequenced with short reads. Non-oak reads were extracted from these data and queried to microbial databases. Reads uniquely matching AOD-associated bacterial genomes were found to be present on trees from all five sites and included trees with active lesions, trees with historic lesions and trees without AOD symptoms. The abundance of the AOD-associated bacteria did not differ between tree health categories but did differ among sites. We conclude that the AOD-associated bacteria may be members of the normal oak microbiome, whose presence on a tree is not sufficient to cause AOD symptoms.

Coronavirus disease 2019 (COVID-19) caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached a global epidemic across the world after first reported in Wuhan, China’s Hubei province in December 2019. The pandemic is also associated with acute respiratory distress syndrome (ARDS) characterized by excess inflammation, progressive arterial hypoxemia and dyspnea. Mesenchymal stem/ stromal cells (MSCs) have been investigated as treatment for ARDS due to immunomodulatory property. Exosomes derived from MSCs play an important role in paracrine signaling of MSCs, thereby contributed to immunomodulation of the immune microenvironment. Exosomes are emerged as potential alternative to MSC cell therapy with superiority of safety. In this review, we will introduce MSC-derived exosomes and briefly discuss current progress on MSCs and exosomes in ARDS, which may have clinical implications in pathogenesis and treatment of COVID-19.

Intrauterine growth restriction (IUGR) and being born small for gestational age (SGA) are two distinct conditions with different implications for child development. IUGR is associated with greater perinatal morbidity and mortality and can be identified by additional abnormalities (pathological Doppler sonography, oligohydramnios, lack of growth in the interval, estimated weight <3rd percentile). IUGR may also be present in neonates with birth weights above the 10th percentile. Recognizing fetuses being “at risk” of a higher perinatal mortality and morbidity rate in order to monitor them accordingly and deliver them in good time is still challenging. This review article summarizes approaches to increase the diagnostic accuracy of IUGR and presents current concepts of pathophysiology with a focus on oxidative stress and consecutive inflammatory and metabolic changes. Since prenatal influences affect the risk of later diseases, we also discuss the need for interdisciplinary follow-up strategies during childhood and look at future scientific challenges. It should be emphasized that prenatal and postnatal care of IUGR neonates should be regarded as a continuum.

Background: The incidence of traumatic acute subdural hematomas (ASDH) in elderly is increasing. Despite surgical evacuation, these patients have poor survival and low rate of functional outcome, and surgical timing plays a no clear role as predictor. We investigated if the timing of surgery has a major role in influencing outcome in these patients.Methods: We retrospectively retrieved clinical and radiological data of all patients ≥70 years operated on for post-traumatic ASDH in a 3 years period in 5 Italian Hospitals. Patients were divided in 3 surgical timing groups from hospital arrival: ultra-early (within 6h); early (6-24h); delayed (after 24h). Outcome was measured at discharge using two endpoints: survival (alive/dead) and functional outcome at Glasgow Outcome Scale (GOS). Univariate and multivariate predictor models were constructed.Results: We included 136 patients. About 33% died for consequences of ASDH and among the survivors only 24% were in good functional outcome at discharge. Surgical timing groups appeared different according to presenting GCS, which was on average lower in ultra-early surgery group, and radiological findings, which appeared worse in the same group. Delayed surgery was more frequent in patients with subacute clinical deterioration. Surgical timing appeared associated neither with survival nor with functional outcome also after stratification for preoperative GCS. Preoperative midline shift was the strongest outcome predictor. Conclusions: An earlier surgery was offered to patients with worse clinical-radiological findings. Also after stratification for GCS it was not associated with better outcome. Among the radiological markers, preoperative midline shift was the strongest outcome predictor.

The relationship between arterial stiffness and oxygen uptake (VO2) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to investigate this relationship and factors contributing to VO2 in patients with AMI. The role of arterial stiffness in cardiac-skeletal muscle coupling during exercise was then elucidated. The exercise capacity via cardiopulmonary exercise testing (CPX), cardio-ankle vascular index (CAVI), and body composition of 101 patients with AMI were measured at discharge. Patients were categorized based on their CAVI into three groups: (i) normal (CAVI: ≤7.9), (ii) borderline (CAVI: 8.0–8.9), and (iii) abnormal (CAVI: ≥9.0). Subsequently, VO2 was compared among these groups. The relationship between the CAVI and peak VO2 (VO2 Peak) during CPX and factors contributing to VO2 Peak were investigated. The abnormal CAVI group had a significantly lower VO2 Peak than the normal and borderline groups. The CAVI was associated with VO2 Peak in patients with AMI. Furthermore, the CAVI was found to be a factor contributing to VO2 Peak. These findings suggest that arterial stiffness in tissue blood distribution and blood supply defines systemic exercise limits in patients with AMI. This suggested that arterial stiffness plays a significant role in cardio-vascular-skeletal muscle coupling.

Introduction: The 2019 novel coronavirus (COVID-19) is very contagious, and can be transmitted to other people by droplet, aerosol, sneezing, infected surface, and cough. There is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. Method: We searched all relevant literature published up to February 28, 2020, from Embase, Scopus, PubMed, Web of Science, and the Cochrane library to collect the studies that reported clinical and laboratory characteristics of COVID-19 infected patients. The study quality was assessed with the Critical Appraisal Checklist. Depending on the heterogeneity test, we used either random or fixed-effect models to analyze the appropriateness of the pooled results. Result: Twenty studies were included in the meta-analysis, including a total of 52,251 patients with confirmed COVID-19 infection. 69.5% (95% CI 54.5-81, p < 0.001) of patients had a history of recent travel to Wuhan, contact with people from Wuhan, or lived in Wuhan. The most common symptoms among COVID-19 infected patients were fever 85.6 % (95% CI 73 -93, p < 0.001), and cough 63 % (95% CI 55.5-70, p < 0.001), respectively. The laboratory analysis showed that thrombocytosis was present in 91% (95% CI 81-98, p < 0.001) CRP was elevated in 81% (95% CI 65-91, p < 0.001), and lymphopenia in 62.5% of cases (95% CI 42-79, p < 0.001). The most common radiographic signs were bilateral involvement in 76.8% (95% CI 62.5-87, p < 0.001) and consolidation in 75.5% (95% CI 50.5-91, p < 0.001) of patients. Most patients (85.4%) were hospitalized, 20.6% of patients were admitted to the ICU in critical condition, and the mortality rate was 5.6%. Conclusions: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. The most common radiographic sign was bilateral involvement in and consolidation. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.

Introduction: Despite more than one year passed since the first cases of SARS-CoV-2 were reported, there is still no consensus on the definition and clinical management of post-acute-COVID-19. The condition has heterogeneously been named as Chronic COVID syndrome, Post COVID-19 Syndrome, post-acute sequela of SARS-CoV-2 (PASC), and the more familiar long COVID. Method: In order to capture all relevant published studies, we undertook a multi-step search with no language restriction. The following four-step search strategy was utilized: First, a preliminary (limited) search was conducted on January 20, 2021, in Google Scholar and PubMed to identify the appropriate keywords. Then, on January 30, 2021, we adopted a search strategy of electronic databases from Cochrane Library, PsycINFO, PubMed, Embase, Scopus, and Web of sciences, using those keywords. Then, after duplicate removal, we screened all titles, abstracts, and full texts. This resulted in 66 eligible studies. Subsequently, after a forward and backward search of their references and citations an additional 54 publications were found, resulting in a total of 120 publications that formed the basis of the present analysis. The titles, abstracts, and full-texts of non-English articles were translated using Google Translate for further evaluation. We conducted our scoping review based on the PRISMA-ScR Checklist.Results: We found only one randomized clinical trial in our search. Of the 67 original studies, 22 were cohort and 28 were cross-sectional studies totaling 74.6% of the original studies. Of the total of 120 publications, 59 (49.1%) focused on signs and symptoms, 28 (23.3%) were focused on management, and 13 (10.8%) focused on pathophysiology. Ten (9%) publications focused on imaging studies. Ninety-one percent of the original investigations came from high and upper-middle-income countries, highlighting the scarcity of reports originating from low-income and lower-middle-income countries.Conclusion: The predominant symptoms among those with the so-called “Long COVID” were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. The ambiguity and controversies in its definition have impaired proper recognition and management of those requiring additional support following the resolution of the acute phase of this infection. This has resulted in long-standing distress for the patients and their families. Our findings highlight the need for a multidisciplinary approach, support, and rehabilitation for these patients in terms of long-term mental and physical health.

Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following FDA guidance. At Day 1 (diagnosis) the mean(SD) sum score of the six ACSS typical symptoms reached 10.60(2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favoured ACSS criteria (sum score of typical symptoms 0.98(1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. Conclusion The American-English ACSS showed high predictive ability and responsiveness, and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice or for self-diagnosis of women with symptoms of UC.

Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. This study aimed to test the efficacy of a newly-developed symptom self-management program on health outcomes among inpatients post-AMI. A pilot randomised, controlled trial was utilised. A convenience sample of 90 was recruited from a tertiary hospital in Singapore. Adult inpatients with post-AMI were randomly assigned to the three groups: IManage-HSet, IManage-FF or control group. Sample size was computed using power analysis. Data were collected through self-reported questionnaires and physiological instruments. Data analyses included univariate statistics, analysis of variance and repeated measure analysis of variance. Ninety participants were recruited with 30 in each group. Participants in the IManage-HSet and IManage-FF group had significantly greater relaxation (ηp2 = 0.11), lower objective stress (ηp2 =0.14), and greater knowledge (ηp2 = 0.62) than those of the control group. The two intervention groups had lower subjective stress (ηp2 = 0.04), depression (ηp2 = 0.01), and anxiety (ηp2 = 0.03) than the control but such differences did not achieve statistical significance. Furthermore, most participants reported that they were satisfied with the programs and they provided positive comments on the contents, educational materials and relaxation practice. This pilot study supports the potential benefits and feasibility of the IManage-VR and IManage-FF interventions on stress, perceived relaxation, knowledge and patient satisfaction. Contents of the symptom management interventions could be added into current cardiac rehabilitation programs. Future RCTs with multi-centered sites and larger sample size are required to further test the intervention. This study was prospectively registered with the International Standard Randomised Controlled Trial on the 5th August 2014 with registration number ISRCTN61027816.

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcifica-tion, inflammation, and plaque vulnerability. They also participate in the vascular re-sponse during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evalua-tion of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant atten-tion. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognos-tic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an in-flammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunc-tion, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quan-titative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovas-cular events (MACE) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying cor-onary inflammation and subsequent high-risk plaque. These findings have been sup-ported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door to a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary pre-vention and intensive secondary prevention in patients at higher risk of cardiac events.

Leukemia is a cancer of the bone marrow, a spongy tissue that secretes into the bones and serves as the site for the production of blood cells. One of the most prevalent kinds of leukemia in adults is acute myeloid leukemia (AML). Leukemia has non-specific signs and symptoms that are also similar to those of other interpersonal illnesses. The only way to accurately diagnose leukemia is by manually examining a stained blood smear or bone marrow aspirate under the microscope. However, this approach takes more time and is less precise. This paper describes a method for the automatic recognition and classification of AML in blood smears. Classification techniques include decision trees, logistic regression, support vector machines, and naive bayes.

Prolonged exercise induces acute renal injury; however, the precise mechanism remains unclear. We investigated the effects of neutrophil depletion in male C57BL/6J mice. Male C57BL/6J mice were divided into four groups: sedentary with control antibody, sedentary with antineutrophil antibody, exhaustive exercise with control antibody, and exhaustive exercise with antineutrophil antibody. Antineutrophil (1A8) or control antibody was administered intraperitoneally to the mice prior to their running on a treadmill. Renal histology was assessed 24 h after exhaustive exercise, and the concentration of kidney injury molecule (KIM)-1 was measured using enzyme-linked immunosorbent assay. The expression levels of inflammatory cytokines were measured using quantitative reverse transcriptase-polymerase chain reaction. Furthermore, nicotinamide adenine dinucleotide phosphate oxidase activity and hydrogen peroxide concentration in the kidneys were measured. The pathologic changes were manifested as congested and swollen glomeruli, tubular dilatation, and nuclear infiltration after exhaustive exercise. These changes were suppressed by the administration of the 1A8 antibodies. KIM-1 concentration increased after exhaustive exercise but were reduced by the 1A8 antibodies. Treatment with the 1A8 antibody also decreased exhaustive exercise-induced inflammation and reactive oxygen species levels in the kidney. These results suggest that neutrophils contribute to exercise-induced acute renal injury by regulating inflammation and reactive oxygen species levels.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.

Acute myeloid leukemia (AML) is a hematological malignancy that predominantly affects the elderly. Prognosis declines with age. For those who cannot tolerate intensive chemotherapy, historically established treatment options have been hypomethylating agents (HMAs), low dose cytarabine (LDAC), and best supportive care (BSC). As the standard of care evolves for those unfit for intensive chemotherapy, there is a need to understand established treatment pathways, clinical outcomes and healthcare resource utilization in Canada. The CURRENT study was a retrospective chart review of AML patients not eligible for intensive chemotherapy who initiated first-line treatment between 1 January 2015 and 31 December 2018. Data were collected from 170 Canadian patients treated at six hematology centers, of whom 118 received systemic therapy and 52 received BSC as first-line treatment. Median overall survival was 8.58 months and varied from 2.96 months for BSC to 13.31 months for HMAs. Over 80% of patients had at least one outpatient visit, and 67% of patients receiving systemic therapy and 71% of those receiving BSC had at least one admission to hospital, during their first line of therapy. A total of 96 (81.4%) patients receiving first line systemic therapy and 39 (75.0%) of those receiving first line BSC had at least one red blood cell or platelet transfusion. These findings highlight the unmet need for novel therapies for patients ineligible for intensive chemotherapy.

Background: Disentangling adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates. Vancomycin and amikacin are perceived as nephrotoxic and often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as sensitive tool to detect a renal impairment signal. Methods: A recently developed dynamical model that characterized serum creatinine concentrations of 217 ELBW neonates (4036 serum creatinine observations) was enhanced with data on individual administration of vancomycin and/or amikacin to identify a potential effect of antibiotic exposure by nonlinear mixed-effects modelling analysis. Results: Of our ELBW patients, 77% were exposed to either vancomycin or amikacin. Antibiotic exposure resulted in transient lower overall creatinine clearance and a modest increase in serum creatinine. Dependency on gestational age was observed in the difference in serum creatinine when exposed to antibiotics during the third week after birth (difference in creatinine for a neonate at 24 weeks gestation decreased with 56% for a 32-week-old neonate). Conclusions: A previously described model on creatinine dynamics was used to explore and quantify the impact amikacin or vancomycin exposure on creatinine dynamics. Such tools can be used to explore minor changes, or compare minor differences between treatment modalities.

AIM: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in gastrointestinal and hepatobiliary surgeries. Material and methods: All the gastrointestinal surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant Results: We performed 331 gastrointestinal and hepatobiliary surgery from April 2018 to March 2020. After exclusion 317 patients were included in study population.14 patients (4.4%) were defined as having acute kidney injury according to acute kidney injury network classifications. On univariate analysis acute kidney injury was associated with open surgery (p= 0.002, Intra operative hypotension (p=0.006), CDC grade of surgery (p<0.001), increased used to blood products (p=0.004), higher ASA grade (p<0.0001), increased operative time(p<0.0001). On multivariate logistic regression analysis higher ASA grade (p=0.001) and increased operative time (0.015) independently predicted acute kidney injury. Acute kidney injury was also significantly associated with 90 days mortality. ( p= <0.0001) Conclusion:Post-operative acute kidney injury was associated with significant mortality in gastrointestinal and hepatobiliary surgery. Open surgery, higher CDC grade surgery, more blood products, higher ASA grades, increase operative time predicted acute kidney injury in post operative periods. Higher ASA grades and increased operative time predicted acute kidney injury.

Background: After allogeneic hematopoietic stem cell transplantation (allo-HSCT), acute leukemia relapse is common, and asymmetric bone marrow recurrence hasn’t been reported. Because the anatomical distribution of acute leukemia clones in the bone marrow after allo-HSCT is presumed to be diffuse, bone marrow aspirations are performed in single site. Case presentation: We identified two acute leukemia patients, whose leukemic burden in bilateral bone marrow specimens differed significantly. The first case was a 20-year-old man who was diagnosed with acute myelomonocytic leukemia and received haploidentical allo-HSCT. He had been in complete remission for two years and off immunosuppressive medications for a year, with normal peripheral blood count. Routine bone marrow biopsy of his left posterior iliac bone marrow showed 52% leukemia blasts, while the right side had 0% blasts ten days later. Due to the discordant results, the patient refused further intervention and died of high leukocyte syndrome four months later. The second case was a 23-year-old woman who was diagnosed with acute B lymphoblastic leukemia and received HLA-identical sibling allo-HSCT. Although 62% of blasts were found in her left iliac marrow on day +122, 0 % of blasts were found on a sample obtained from the right iliac crest on day +128. Whole-body 18F-FDG PET/CT scans confirmed that the leukemic infiltration in her bone marrow was asymmetric. Considering the higher leukemic burden on the left, we chose the left posterior iliac crest aspiration for further response evaluation. After chemotherapy combined with donor lymphocyte infusion, she achieved transient hematologic complete remission. She died of septic shock with heart failure at +258 days after allo-HSCT before infusion of anti-CD19 donor chimeric antigen receptor T cells. Conclusions: To our knowledge, these are the first case reports of asymmetric bone marrow infiltration of blasts in acute leukemia patients after allo-HSCT. Bilateral posterior iliac crest aspirations or 18F-FDG-PET/CT scans may help distinguish such distribution. If discordant bone marrow specimens are observed, physicians should restrict future bone marrow studies to the more involved side.

Long non-coding RNA (lncRNA) aberrant expression have been found in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped in transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated in pediatric ALL and uc.112 expression was higher in T-ALL compared to patients with B-ALL and in patients with hyperdiploid karyotype. These findings suggest a potential role of this uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

Multiple lines of evidence indicate that CD8$^+$ T cells are important in the control of HIV-1 (HIV) replication. However, CD8$^+$ T cells induced by natural infection cannot eliminate the virus or reduce viral loads to acceptably low levels in most infected individuals. Understanding the basic quantitative features of CD8$^+$ T-cell responses induced during the course of HIV infection may therefore inform us about the limits that HIV vaccines, which aim to induce protective CD8$^+$ T-cell responses, must exceed. Using previously published experimental data from a cohort of HIV-infected individuals with sampling times from acute to chronic infection we defined the quantitative properties of CD8$^+$ T-cell responses to the whole HIV proteome. In contrast with a commonly held view, we found that the relative number of HIV-specific CD8$^+$ T-cell responses (response breadth) changed little over the course of infection (first 400 days post-infection), with moderate but statistically significant changes occurring only during the first 35 symptomatic days. This challenges the idea that a change in the T-cell response breadth over time is responsible for the slow speed of viral escape from CD8$^+$ T cells in the chronic infection. The breadth of HIV-specific CD8$^+$ T-cell responses was not correlated with the average viral load for our small cohort of patients. Metrics of relative immunodominance of HIV-specific CD8$^+$ T-cell responses such as Shannon entropy or the Evenness index were also not significantly correlated with the average viral load. Our mathematical-model-driven analysis suggested extremely slow expansion kinetics for the majority of HIV-specific CD8$^+$ T-cell responses and the presence of intra- and interclonal competition between multiple CD8$^+$ T-cell responses; such competition may limit the magnitude of CD8$^+$ T-cell responses, specific to different epitopes, and the overall number of T-cell responses induced by vaccination. Further understanding of mechanisms underlying interactions between the virus and virus-specific CD8$^+$ T-cell response will be instrumental in determining which T-cell-based vaccines will induce T-cell responses providing durable protection against HIV infection.

Active vitamin D derivatives (VDDs) – 1α,25-dihydroxyvitamin D3/D2 and their synthetic analogs – are well-known inducers of cell maturation with the potential for differentiation therapy of acute myeloid leukemia (AML). However, their dose-limiting calcemic activity is a significant obstacle to using VDDs as an anticancer treatment. We have shown that different activators of the NF-E2-related factor-2/Antioxidant Response Element (Nrf2/ARE) signaling pathway, such as the phenolic antioxidant carnosic acid (CA) or the multiple sclerosis drug monomethyl fumarate (MMF), synergistically enhance the antileukemic effects of various VDDs applied at low concentrations in vitro and in vivo. This study aimed to investigate whether glutathione, the major cellular antioxidant and the product of the Nrf2/ARE pathway, can mediate the Nrf2-dependent differentiation-enhancing activity of CA and MMF in HL60 human AML cells. We report that glutathione depletion using L-buthionine sulfoximine attenuated the enhancing effects of both Nrf2 activators concomitant with downregulating vitamin D receptor (VDR) target genes and the activator protein-1 (AP-1) family protein c-Jun levels and phosphorylation. On the other hand, adding reduced glutathione ethyl ester to dominant negative Nrf2-expressing cells re-stored both the suppressed differentiation responses and the downregulated expression of VDR protein, VDR target genes, as well as c-Jun and P-c-Jun levels. Finally, using the transcription factor decoy strategy, we demonstrated that AP-1 is necessary for the enhancement by CA and MMF of 1α,25-dihydroxyvitamin D3-induced VDR and RXRα protein expression, transactivation of the vitamin D response element, and cell differentiation. Collectively, our findings suggest that glutathione mediates, at least in part, the potentiating effect of Nrf2 activators on VDDs-induced differentiation of AML cells, likely through the positive regulation of AP-1.

RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.

Although automated Acute Lymphoblastic Leukemia (ALL) detection is essential, it is challenging due to the morphological correlation between malignant and normal cells. The traditional ALL classification strategy is arduous, time-consuming, often suffers inter-observer variations, and necessitates experienced pathologists. This article has automated the ALL detection task, employing deep Convolutional Neural Networks (CNNs). We explore the weighted ensemble of deep CNNs to recommend a better ALL cell classifier. The weights are estimated from ensemble candidates' corresponding metrics, such as accuracy, F1-score, AUC, and kappa values. Various data augmentations and pre-processing are incorporated for achieving a better generalization of the network. We train and evaluate the proposed model utilizing the publicly available C-NMC-2019 ALL dataset. Our proposed weighted ensemble model has outputted a weighted F1-score of 88.6%, a balanced accuracy of 86.2%, and an AUC of 0.941 in the preliminary test set. The qualitative results displaying the gradient class activation maps confirm that the introduced model has a concentrated learned region. In contrast, the ensemble candidate models, such as Xception, VGG-16, DenseNet-121, MobileNet, and InceptionResNet-V2, separately produce coarse and scatter learned areas for most example cases. Since the proposed ensemble yields a better result for the aimed task, it can experiment in other domains of medical diagnostic applications.

Acute kidney injury (AKI) is a complication that can occur after cardiac surgery and requires ongoing research in light of the exponential expansion of technological advancements and knowledge in medicine. In this study, we aim to evaluate the outcomes of treated electives of emergency aortic disease with high serum creatinine levels (SCr). Methods: The cohort includes 183 patients, all of whom have an aortic disease and whose SCr levels were checked upon admission on the first day in the intensive care unit (ICU) and upon discharge from the hospital. We examined the correlation of SCr levels with in-hospital mortality and immediate mortality at least six months after discharge as well as with cross-clamp time and bypass time.Results: A high SCr level upon admission is a significant predictive factor of n-hospital mortality (p = 0.001) but not immediate mortality (p = 0.409). A statistically significant correlation was also observed between elevated SCr level on the first day of ICU and aortic disease (p = 0.041) but not immediate mortality (p = 0.119). We observed a significant correlation between aortic disease and in-hospital mortality (p < 0.001), but no correlation was found between high SCr level on the first day of ICU and immediate mortality (p = 0.119). The cross-clamp time is statistically significant correlated with elevated SCr level (p = 0.013) and in-hospital mortality (p = 0.001) but not immediate mortality (p = 0.847). Furthermore, the bypass time is negatively correlated with a high SCr level on the first day of ICU (p = 0.090), in-hospital mortality (p = 0.410), and immediate mortality (p = 0.625). We also found that aortic disease is not correlated with elevated creatinine levels at ICU discharge (p = 0.152) or long-term mortality (p = 0.106). Conclusions: Although this study only included a small portion of the elaborate aspects of surgical and medical management developed around cardiac patients who received invasive treatment, the conclusions reached are nevertheless clearly relevant, as evidenced by the significantly correlations uncovered. In order to manage AKI after AAS and improve the outcome, the SCr level could be used as a marker for renoprotective strategy. Moving forward, these results serve as a first step in motivating us to expand the range of our research, collect newly relevant data, and use it to benefit patients.

The short-term intake (ESTI) of Hungarian consumers to pesticide residues was assessed based on 2331 test results obtained during 2017-2021 monitoring program in the frequently analyzed apples, sour cherries, table grapes, peaches, nectarines, peppers and strawberries (23.5% of all samples taken from 119 crops). The age-specific consumption data were obtained from two representative national food consumption surveys (2009 and 2018-2020). The exposure was characterized with Hazard Quotient and Hazard Index considering the acute reference doses of pesticide residues detected in the samples. When ESTI was calculated with all detected “single“ residues and variability factor of 3.6, recommended for evaluation of monitoring results, the HI only exceeded 1 for children &lt;3 years old eating grape (1.50-1.81). HI was &lt;1 when any of the 6 foods were eaten together within one day. Between forty and fifty percent of samples contained 2-23 residues. Though, the individual residue concentrations were below the corresponding MRLs, multiple residues being present in one sample resulted in maximum HI values in apples (1.14); grapes (6.57); peaches and nectarines (2.57); strawberries (2.74); peppers (10.44). Residues with low ARfD values contributed most. Applying HI is simple, but provides only point estimates; therefore, it should only be used in first-tier risk assessment.

Background Acute kidney injury (AKI) is a common comorbidity in the intensive care unit (ICU), with higher mortality rate among those who receive continuous renal replacement therapy (CRRT). This study aimed to investigate the association of white blood cell (WBC) levels with all-cause mortality in AKI patients undergoing CRRT. Method We conducted a post hoc analysis of ICU patient data from multiple centers in Korea. First, the levels of WBCs were classified into four groups based on quartiles. Second, the relationship between different WBC levels and mortality was investigated with the Kaplan-Meier (K-M) survival curves, Cox proportional hazards model, and generalized additivity model (GAM). Finally, we used multiple imputation to avoid bias caused by non-randomized missing data. The endpoints were short-term (28 days) and long-term (90 days) mortality. Result In our analysis, a total of 1,100 ICU patients were included. Among them, 670 (60.90%) and 781 (71.00%) died within 28 and 90 days, respectively. K-M survival curves showed that patients with the lowest WBC levels had the highest risk of mortality for both outcomes. Adjusted multivariate Cox regression analysis confirmed that compared with the reference level (quartile 2), low WBC levels increased the risk of both 28-day mortality (quartile 1, HR = 1.43, 95% CI: 1.13–1.83, P = 0.004) and 90-day mortality (quartile 1: HR = 1.32; 95% CI: 1.05-1.66, P = 0.016). GAM analysis showed a non-linear, U-shaped relationship between pre-CRRT WBC levels and all-cause mortality (non-linear P < 0.05). Conclusion The baseline WBC level is an independent predictor of prognosis for ICU patients receiving CRRT. Patients in the lowest WBC quartile had the highest risk of all-cause mortality. These results provide further evidence that early observation and intervention may have a prognostic value for these high-risk patients.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

Kidney diseases are a global health problem, and their frequency is continuously increasing. Available treatments provide limited kidney protection. The protective effect of the green tea polyphenol epigallocatechin-3-gallate (EGCG) in several diseases have been extensively investigated. Experimental and clinical studies have shown that the antioxidant, anti-inflammatory, and anti-apoptotic properties of EGCG are promising for the treatment and/or prevention of kidney diseases. This review analyzes the available evidence on the effects, and the likely protective mechanisms of action, of EGCG in a broad spectrum of kidney diseases, including acute kidney injury, drug-induced nephrotoxicity, kidney stone disease, diabetic nephropathy, chronic kidney disease, and kidney fibrosis.

This study aimed to investigate the potential correlations and differences between patients with Acute Coronary Syndrome (ACS) and controls. Emphasis was placed on examining the relationship between arterial blood gas PH value and arterial blood gas lactate value as well as assessing the utility of the Peripheral Perfusion Index (PI) in ACS management. Materials and Methods: A prospective observational study was conducted between January 1, 2023, and July 1, 2023, involving 60 ACS patients and 30 control subjects in an emergency department. The diagnosis of ACS was confirmed by experienced emergency physicians, and various parameters, such as peripheral perfusion index, blood gas values, and cardiac biomarker values, were collected. The statistical analyses included Pearson’s chi-square test, Mann-Whitney U test, Student’s t-test, and others, using SPSS version 18.0. There were significant differences in the mean age, perfusion index, and lactate levels between the patient and control groups. A robust negative correlation was found between age and PI, and a moderate negative correlation was observed between pH and lactate levels (r = -0.301, p=0.004). The perfusion index in the patient group was significantly lower, indicating its potential diagnostic utility. The findings demonstrate the importance of arterial blood gas pH and lactate values in understanding ACS patient profiles, emphasizing the potential of PI as a noninvasive diagnostic method. The negative correlation between pH and lactate levels may offer valuable insights into risk stratification and treatment strategies for patients with ACS.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study we investigate the clinical use in these directions of a “damage” type biomarker - Neutrophil Gelatinase-Associated Lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasmsa NGAL was determined at baseline, at 4 and 24 hours after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (132.33±72.83 ng/ml versus 111.48±65.06 ng/ml, p=0.006) and at the 24th hour (212 .93±276.61 ng/ml, p=0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (128.18±99 ng/ml, p=0.002) and reached levels close to those in patients with CI-AKI. Unlike new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good - AUC 0.847 (95% CI: 0.677-1.000; p=0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539 – 0.924; p=0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

Background/Objectives: Bacterial infections (BI) are a major cause of mortality in patients with alcohol-associated hepatitis (AH); however, only a few studies have investigated BI in AH in the last decade. Therefore, we aimed to assess the features and outcomes of BI in patients with AH. Methods: This observational descriptive study included patients with AH admitted to a tertiary academic hospital between 2016–2021. Clinical and complete microbiological data were recorded and complications, including acute-on-chronic liver failure (ACLF), and mortality over 90-days were compared between infected and non-infected patients. Results: Overall, 115 patients with AH were recruited and 75 had severe AH; among them, 66 started corticosteroid treatment. We identified 69 cases of BI in 44 patients; the incidence of BI at hospital discharge was 32.2%, which reached 38.2% at 90 days. The predominant infection site was the chest (35%). Among the identified bacteria (52.1%), half were gram-positive and half gram-negative. A low rate of multidrug-resistant bacteria (14%) was also noted. Infected patients during hospitalization (n=37) exhibited higher rates of hepatic decompensation and ACLF p=0.001) and lower survival (81.8% vs. 95.8%, p=0.015) than did non-infected patients (n=78). In-hospital infected patients (n=22) exhibited worse survival (72.7%) than did those infected upon admission (93.3%) or non-infected patients (94.9%) (p=0.009). Corticosteroid-treated patients displayed a nonsignificant increase in the total number of BI; however, without greater mortality. Conclusions: BI were common in our cohort of patients with AH. Patients with in-hospital infections commonly experienced serious complications, including high ACLF and death rates. Infections diagnosed upon admission were treated without affecting survival.

Transplant of human cancer cells into zebrafish larvae has emerged as a useful methodology in cancer research. Zebrafish have very low husbandry costs, are amenable to large-scale drug screening, and are unmatched for optical clarity in live animal imaging. However, there is currently no consensus on the ideal methods for xenograft of human cancer cells into zebrafish. Here, we have examined the effects of transplant site and housing temperature on both zebrafish larvae and human cancer cells using survival analyses, metabolomic approaches, and in vivo imaging. Our data show that while zebrafish larvae can adapt to the ideal conditions for mammalian cells, human cancer cells are highly sensitive to both temperature change and transplant site. Human cells housed in slightly cooler than physiologic temperatures had a significantly altered metabolism that resulted in changes in growth, survival, and response to chemotherapy. Cancer cells xenografted into the yolk of the larvae also had reduced proliferation and drug response compared to those xenografted into the soma, in part due to the differences in metabolites available at these sites. In total, temperature and transplant site can have profound effects on xenografted cells. Standardization of zebrafish xenograft methods will enhance data reproducibility between individual laboratories.

Background and Objectives: Acute Heart Failure (AHF) is a common disease and a cause of high morbidity and mortality, constituting a major health problem. The main purpose of this study was to determine the impact of multiorgan ultrasound in identifying the pulmonary hypertension (PH) in patients admitted due to AHF, predict the evolution of the disease during hospitalization and identify areas of improvement in the care of patients with AHF. Materials and Methods: Patients were evaluated with a standard exam of lung ultrasound, echocardiography, inferior vena cava (IVC) and femoral, renal, hepatic, portal venous Doppler flow patterns at admission and on the day of discharge. Results: Thirty patients were enrolled during November 2021. The mean age was seventy-nine years (Standard Deviation – SD 13,4). Seven patients (23.3%) had a renal function worsening. Regarding ultrasound findings, venous excess ultrasonography score (VExUS) score was calculated at admission and at discharge, surprisingly remaining unchanged or even worsened in most of them (21 patients, 70.0%). The area under the curve for the Lung Score was 83.9% (p = 0.008), obtaining a cutoff value of 10 that showed a sensitivity of 82.6% and a specificity of 71.4% in the identification of intermediate and high PH. It was possible to monitor significant changes between both exams on the lung score (p &lt;0.001), hepatic vein Doppler (p &lt;0.001), portal vein Doppler (p = 0.030), intra-renal vein Doppler (p = 0.025) and VExUS score (p = 0.023), remaining similar the femoral vein Doppler (p = 0.177) and IVC (p = 0.132). Conclusions: Our study results suggest that performing serial multiorgan Point-of-Care ultrasound can help us to better identify high and intermediate probability of PH patients with AHF. Currently proposed multi-organ, venous Doppler scanning protocols, such as the VExUS score, should be further studied in different populations before expanding its use in AHF patients.

There is remarkable morphologic and genetic heterogeneity in acute myeloid leukemia (AML). In a small percentage of cases of AML, increased eosinophils and/or basophils are present in the bone marrow and sometimes in the peripheral blood. This is often a puzzling diagnostic situation but also an important finding that requires special investigation. Unique chromosomal rearrangements have been correlated with an increased number of eosinophils and basophils in AML. Identification of the underlying genetic lesion that promotes eosinophilia and basophilia can dramatically change both the prognosis and the treatment of the patient. Thus clinicians must be vigilant in searching for the cause of eosinophilia and/or basophilia in patients with AML, since the different causes may lead to different treatments and survival outcomes. In this article we examine the significance of increased eosinophils and/or basophils in the context of AML, provide guidance that simplifies the differential diagnosis, and prognostic and therapeutic information about specific subtypes of AML associated with eosinophilia and/or basophilia. Evidence supporting personalized (molecularly targeted) therapy for these patients is also presented.

A considerable number of infective endocarditis (IE) patients require cardiac surgery with an increased risk for postoperative sepsis. Intraoperative hemoadsorption may diminish the risk of postoperative hyperinflammation with potential economic implications for intensive care unit (ICU) occupation. The present study aimed to theoretically investigate the budget impact of a reduced length of ICU stay in IE patients treated with intraoperative hemoadsorption in the German healthcare system. Data on ICU occupation were extrapolated from a retrospective study on IE patients treated with hemoadsorption. An Excel-based budget impact model was developed to simulate the patient course over the ICU-stay. A base-case scenario without therapy reimbursement and a scenario with full therapy reimbursement were explored. The annual eligible German IE patient population was derived from official German Diagnostic Related Group (DRG) volume data. One-way deterministic sensitivity analysis and bootstrap analysis were performed to evaluate the uncertainty over the model results. Use of intraoperative hemoadsorption resulted in 2,298€ saved per patient in the base-case scenario without therapy reimbursement. Savings increased to 3,804€ per patient in case of full device-specific reimbursement. Deterministic and probabilistic sensitivity analyses confirmed the robustness of savings, with a probability of savings of 99% and 100% in the base-case and full reimbursement scenario, respectively. Intraoperative hemoadsorption in IE patients might have relevant economic benefits related to reduced ICU stay, resulting in improved resource use. Further evaluations in larger prospective cohorts are warranted.

Initially, renal resistive index (RRI) was investigated to improve diagnosis in kidney diseases, but failed to meet this goal. Recently many papers highlighted the prognostic significance of RRI in chronic kidney disease, in the estimation of revascularization success of renal artery stenoses or the evolution of the graft and recipients in renal transplantation. Moreover, RRI gained importance in prediction of acute kidney injury in critically ill patients. Along with RRI study in renal pathology have been revealed correlations of this index with parameters of systemic circulation. The theoretical and experimental premises of this connection were reconsidered, and studies for analyzing the link between RRI and arterial stiffness, central and peripheral pressure or left ventricular flow were conducted with this purpose. A high amount of data is currently indicating that RRI is influenced more by pulse pressure and vascular compliance than by renal vascular resistance – assuming that RRI reflects the complex interplay between systemic circulation and renal microcirculation and should be considered as a marker of systemic cardiovascular risk beyond its prognostic relevance for kidney disease. In this review we will go through clinical research that revealed the implications of RRI in renal and cardiovascular disease.

Mild traumatic brain injury (mTBI) or concussion accounts for the bulk of all head injuries and represents a major health concern. Although an mTBI event may not manifest in neurobehavioral impairment, repeated injuries, known as repeated mTBI (rmTBI), can result in a cumulative effect that may progress to long-term cognitive and functional deficits. To date, there is no FDA-approved drug for TBI in general and rmTBI in particular. In previous studies, we have demonstrated the neuroprotective role of mitoquinone (MitoQ), a mitochondrial antioxidant, in an open head injury model and a model of repeated mild TBI (rmTBI) at a chronic time point (30 days). In this work, we set out to assess the neuroprotective potential of MitoQ at acute (3 days) and subacute time points (7 days) post-injury in a controlled cortical impact model of rmTBI. C57BL/6 male mice were injected intraperitoneally with MitoQ (5 mg/kg) one hour after the first mTBI, and three days after the first injury in both the 3-day and 7-day MitoQ + rmTBI subgroups, with an additional injection four days after the second injection in the 7-day group. Cognitive function was evaluated using the Morris water maze (MWM) while gross and fine motor functions were evaluated by the pole climbing, grip strength, and ladder rung tests. Dihydroethidium (DHE) staining was performed to evaluate oxidative stress while qRT-PCR was used to measure the gene expression of different antioxidant enzymes. Also, immunofluorescence staining was performed on brain tissue to assess the degree of microgliosis and astrocytosis. Our results showed that MitoQ conferred significant protection on days 3 and 7 post-injury against fine motor function impairment induced by rmTBI. Moreover, MitoQ enhanced cognitive function and reduced astrogliosis, microgliosis, and levels of oxidative stress on day 7 post-injury. However, antioxidant gene expression generally remained unaffected. In light of our results, MitoQ administration may be considered a preventive approach that helps to alleviate the neurological manifestations associated with rmTBI early before symptoms progress to long-term deficits.

Celecoxib as adjuvant therapy has been shown in a small randomized trial for Covid-19 to prevent clinical deterioration and rapidly improve thoracic computerized axial tomography (CT-chest)¹. Multiple descriptive trials of high dose famotidine (both inpatient and outpatient) have demonstrated clinical response^2,3,4. We describe the rapid clinical responses after increasing the celecoxib dosage to 400mg bid with high dose famotidine 80mg qid in both a critical inpatient who on baseline required 40 liters per minute high flow nasal insufflation and an outpatient who declined admission but had critical Covid-19 biomarkers.

Artificial intelligence methods may help in unveliling information hidden in high-dimensional oncological data. Flow cytometry studies of haematological malignancies provide quantitative data with the potential to be used for the construction of response biomarkers. Many computational methods from the bioinformatics toolbox can be applied to these data but have not been exploited in their full potential in leukaemias, specifically for the case of childhood B-cell acute lymphoblastic leukemia. In this paper we analysed flow cytometry data obtained on diagnosis from 54 paediatric B-cell acute lymphoblastic leukemia patients from two local institutions. We constructed classifiers based on the Fisher’s Ratio to quantify differences in expression levels of immunophenotypical markers between patients with relapsing and non-relapsing disease. The distribution of the marker CD38 was found and validated to have a strong discriminating power between both patient cohorts, thus providing a classifier.

Cardiopulmonary complications remain the major cause of mortality despite newer therapies and improvements in lifespan of patients with sickle cell disease (SCD). Inflammation has been identified as a major risk modifier in the pathogenesis of SCD associated cardiopulmonary complications in recent mechanistic and observational studies. In this review, we discuss recent cellular and molecular mechanisms of cardiopulmonary complications in SCD and summarize the most recent evidence from clinical and laboratory studies. We emphasize the role of inflammation in the onset and progression of these complications to better understand the underlying pathobiological processes. We also discuss future basic and translational research in addressing questions about the complex role of inflammation in the development of SCD cardiopulmonary complications, which may lead to promising therapies and reduce morbidity and mortality in this vulnerable population.

The coronavirus disease 2019 (COVID-19) has spread over the world for more than one year. COVID-19 often develops life-threatening hypoxemia. Endothelial injury caused by the viral infection leads to intravascular coagulation and ventilation-perfusion mismatch. However, besides above pathogenic mechanisms, the role of alveolar edema in the disease progression has not been discussed comprehensively. Since the exudation of pulmonary edema fluid was extremely serious in COVID-19 patients, we bring out a hypothesis that severity of alveolar edema may determine the size of poorly-ventilated area and the blood oxygen content. Treatments to pulmonary edema (alcohol-oxygen vapor therapy and fluid management) may be great helpful for reducing occurrence of severe cases. Given that late mechanical ventilation may cause mucus (edema fluid) to be blown to the deep of the small airways, oxygen therapy should be given at the early stages. The optimal time and SpO₂ threshold for oxygen therapy are also discussed.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

COVID-19 is a highly infectious respiratory illness caused by SARS-CoV-2, and acute lung injury (ALI) is the major cause of COVID-19. The challenge in studying SARS-CoV-2 pathogenicity is the limited availability of animal models. Therefore, it is necessary to establish animal models that can reproduce multiple characteristics of ALI to study therapeutic applications. The present study established a mouse model that has features of ALI that are similar to COVID-19 syndrome to investigate the role of ACE2 and the administration of the Chinese herbal prescription NRICM101 in ALI. Mice with genetic modifications, including overexpression of human ACE2 (K18-hACE2 TG) and absence of ACE2 (mACE2 KO), were intratracheally instillated with hydrochloric acid. The acid intratracheal instillation induced severe immune cell infiltration, cytokine storms, and pulmonary disease in mice. Compared with K18-hACE2 TG mice, mACE2 KO mice exhibited dramatically increased levels of multiple inflammatory cytokines (IL-6, TNF-α, and TGF-β1) in bronchoalveolar lavage fluid, histological evidence of lung injury, and dysregulation of MAPK and MMP activation. In mACE2 KO mice, NRICM101 could ameliorate the disease progression of acid-induced ALI. In conclusion, the established mouse model provided an effective platform for researchers to investigate pathological mechanisms and develop therapeutic strategies for ALI, including COVID-19-related ALI.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

Acute low back pain (LBP) stands as a leading cause of activity limitation and work absenteeism, and its associated healthcare expenditures are expected to become substantial when acute LBP develops into a chronic and even refractory condition. Therefore, early intervention is crucial to prevent progression to chronic pain whose management is particularly challenging and for which the most effective pharmacological therapy is still controversial. Current guideline treatment recommendations vary and are mostly driven by expertise with opinion differing across different interventions. Thus, it is difficult to formulate evidence-based guidance when relatively few randomized clinical trials did explore the diagnosis and management of LBP while employing different selection criteria, statistical analyses, and outcome measurements. This narrative review aims to provide a critical appraisal of current acute LBP management by discussing the unmet needs and areas of improvement from bench-to-bedside and proposes multimodal analgesia as the way forward to attain an effective and prolonged pain relief and functional recovery in patients with acute LBP.

Introduction: Wound healing is a multifaceted biological process, and diabetic wounds add more complexity to it. In diabetic wounds, the combination of chloroform fractions of Achyranthes aspera L. (A.aspera) leaves with β-Glucans has not been investigated. The additive effect of these two (A.aspera + β-Glucans) would benefit the inflammatory phase of diabetic wounds, as improper treatment will lead to chronic injuries. Therefore, the goal of this research work was to assess the in-vivo wound healing and anti-inflammatory effects of a combination of chloroform fractions of A.aspera leaves and β-Glucans in a variety of wound models in STZ-induced diabetic rats. Methods: Preliminary phytochemical analyses of A.aspera were conducted to identify various phytoconstituents in the test extract. Acute and sub-acute dermal toxicity tests of A.aspera were carried out on mice and rats, respectively, to see whether there were any abnormalities. Excision and incision wound models, cotton pellet-induced granuloma models, rat paw edema and burn wounds were used to test wound healing and anti-inflammatory actions. To induce diabetes, streptozotocin (STZ) was administered intraperitoneally at a dosage of 65 mg/kg (i.p.). A.aspera (10% w/w) and β-Glucans (2% w/w) ointments were tested separately and in combination for wound healing activities. Silver sulfadiazine (1 % w/w) ointment was used to treat the positive control groups. Excision wound model rats that had been treated with basic ointment were used as negative controls, as were incision wound model rats that had not been treated. A.aspera (400 mg/kg, po) and β-Glucans (30 mg/kg, po) were tested separately and in combination for anti-inflammatory efficacy. Positive control groups were given indomethacin (10 mg/kg, po) for cotton pellet-induced granuloma and rat paw oedema models. Negative controls for both anti-inflammatory activity models were provided 2% Tween 80. The groups were made up of six rats, and the treatments were given topically and orally to assess wound healing and anti-inflammatory effects. The levels of hydroxyproline and hexosamine and the antioxidant enzymes (SOD and CAT) in the granulation tissue were measured in excision wound model. Healed excision wound skin was examined histopathologically. Results: The A.aspera and β-Glucans combination resulted in a significant percentage of wound contraction and a shorter epithelialization time (P<0.01). The combination was found to be the most effective, with the highest percentage of edema reduction (55 %; p<0.01). The combination also exhibited favourable hydroxylamine, hexosamine and anti-oxidant profiles supported by histopathology data. Conclusion: This research showed that the immunomodulatory effect of β-Glucans had significantly enhanced the wound healing, anti-inflammatory, and anti-oxidant potential of A.aspera in diabetic wounds.

Despite the efforts to deliver the best evidence-based care, in-hospital death is an inevitable event among some patients hospitalized in cardiology departments. We retrospectively evaluated mortality events from inpatient admissions to Cardiology Department between 2010-2019. Data were collected from morbidity &amp; mortality meeting presentations which evaluated comorbidities, medical history, treatments, and causes of death for the overall cohort and according to age group and sex. There were 1,182 registered deaths. The most common causes of death among patients were acute myocardial infarction (AMI) (53.0%), heart failure (HF, 11.7%), cardiac arrest (CA, 6.6%), HF with complication/defined cardiomyopathy (6.3%) and sepsis (4.4%). We observed a decline in deaths from AMI from 61.9% in 2010 to 46.7% in 2019 while there was an apparent increase in deaths from HF (11.1% in 2010 to 25.9% in 2019). Compared to patients ≥65 years, younger patients were more likely to have died from CA (15.7% vs. 4.3%, p&lt;0.001) and other cardiac reasons (3.0% vs. 0.4%, p&lt;0.001). The majority of deaths were due to AMI, HF, and CA. We observed a significant decline in the proportion of deaths due to AMI in recent years with an increase in deaths due to HF.

Abstract: Our goal is to create point-of-care (POC) strategies that accelerate decision making, increase efficiency, improve outcomes, and enhance standards of care in island communities faced with global warming, rising oceans, population migration, and intensifying weather disasters. We assessed needs in the Bantayan Archipelago and mainland Cebu Province, Visayas Islands, Philippines, to map POC diagnostics, rescue times, and spatial care paths. Significant deficiencies were lack of cardiac troponin testing for rapid diagnosis of acute myocardial infarction, absence of blood gas and pH testing for support of critically ill patients, and geographic gaps prolonging patient transfers and delaying treatment. Strengths comprised primary care that can be facilitated by POC testing, logical inter-island transfers for which decision making and triage could be accelerated with onboard diagnostic testing, and healthcare small-world networks amenable to POC advances, such as pre-hospital testing, that avoid overloading emergency rooms. Healthcare resources must be distributed to archipelago islands, not concentrated in large metropolitan areas inaccessible for emergency interventions. We conclude that a point-of-need focus will help improve public health, decrease disparities in mortality among rural islanders versus urban dwellers, and pave the way for heightened resilience in anticipation of the adverse impact of global warming on vulnerable coastal areas.

Estrogens play a protective role during early life stages. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression in low-grade inflammatory conditions like established atherosclerosis. Our single-center cohort study assessed sex-specific associations of gonadal hormones with oxidative stress, inflammation, and myocardial injury markers in 111 patients (37% women) diagnosed with acute myocardial infarction (MI) between July 2011 and December 2013. Blood samples were collected within 48 hours of symptom onset, and we measured sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitive C-reactive protein (CRP), white blood cell counts (WBC), and cardiac enzymes (creatine kinase [CK], the CK Muscle-Brain fraction [CK-MB], and high-sensitive troponin T [hsTnT]). The SYNTAX score gauged coronary disease severity from coronary angiography results. In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels (OR 1.011, p=0.047 - CK; OR 1.018, p=0.013 - CK- MB; OR 1.019, p=0.005 - TnT), peak WBC count (OR 1.487, p=0.015 - CK ; OR 1,709, p=0,005 - CK- MB; OR 1.391, p=0.012 - TnT), and peak CRP plasma levels (OR 1.040, p=0.033 - CK; OR 1.024, p=0.029 - CK-MB; OR 1.063, p=0.006 - TnT). T levels and E2/T ratio were associated with post-PCI CRP in these men (OR 0.980, p = 0.024 - T, OR 1.010, p = 0.076 - CRP). For women, peak WBC was a marker of highest testosterone (OR 1.348, p = 0.062), and only WBC was a significant indicator of myocardial injury extent (OR 1.426, p=0.039 - CK; OR 1.384, p=0.036 - CK-MB; OR 1.299, p=0.048 - TnT). During acute MI, elevated endogenous estradiol levels correlate with myocardial necrosis severity in men, while in women, increased leukocyte levels indicate acute myocardial damage. Elevated plasma T is associated with increased WBC in women. In men, post-PCI plasma CRP specifically indicates endogenous T levels and E2/T ratio during the acute phase.

This comprehensive analysis aims to offer valuable insights into the safety profiles of these glucocorticoids, facilitating the identification of compounds with potentially reduced adverse effects. This study investigates the toxicity profiles of various glucocorticoids, utilizing predictions from the pKCSM Server. Among the glucocorticoids examined, Dexamethasone, Triamcinolone, Hydrocortisone hemisuccinate, Paramethasone, Fluprednisolone, and Flumethasone emerge as potentially less toxic, displaying favorable scores across diverse parameters such as Max. Tolerated Dose (human, MRT), Oral Rat Acute Toxicity (LD50), and Oral Rat Chronic Toxicity (LOAEL). Notably, Hydrocortisone hemisuccinate and Triamcinolone stand out for their high tolerability capacity based on the Max. Tolerated Dose (human, MRT), suggesting enhanced safety profiles. These findings contribute insights into selecting glucocorticoids with optimal safety and tolerability for potential therapeutic applications.Further research and clinical investigations are warranted to validate and refine these findings, ensuring the responsible and effective use of glucocorticoids in medical practice.

Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption; disruptions in this complex can affect bone metabolism. Methods: This study analyzed the changes in RANKL, OPG and 25(OH)D levels, the RANKL/OPG ratio, and other bone turnover markers (BTM) from diagnosis to complete remission in children with acute lym-phoblastic leukemia (ALL). This is a prospective observational cohort study. This study was carried out in the Instituto Mexicano del Seguro Social in Mexico City. Thirty-three patients (4-17 years) with newly diagnosed B-cell ALL were included. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A pe-ripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p=0.001) and osteocalcin (p

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

Atherosclerosis is associated with vascular diseases, diabetes, and cancers. The Jumonji C-domain-containing 6 (JMJD6) gene plays an important role in diverse biological processes. In addition, autoantibodies are reportedly useful in the early diagnosis and treatment of many diseases. Here, JMJD6 was identified by serological identification of antigens by recombinant cDNA expression cloning as an antigen recognized by serum IgG from patients with unstable angina pectoris. Then, we performed amplified luminescent proximity homogeneous assay-linked immunosorbent assay using purified recombinant antigens and found elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with atherosclerosis-related diseases including ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers including esophageal cancer (EC), gastric cancer, lung cancer, and mammary cancer, compared with those in healthy donors. The s-JMJD6-Ab levels were closely associated with hypertension, habitual smoking, and the intima-media thickness, an atherosclerosis index. The better postoperative survival status was shown in patients with EC from the JMJD6-Ab-positive group than the negative group, especially from JMJD6-Ab-positive/PD-L1-negative group and JMJD6-Ab-positive/p53-Ab-negative group than JMJD6-Ab-negative/PD-L1-positive group and JMJD6-Ab-negative/p53-Ab-positive group, respectively. Hence, JMJD6 autoantibodies may reflect atherosclerosis severity, thereby a potential biomarker for atherosclerosis-related diseases including ischemic stroke, AMI, DM, and cancers and for predicting EC prognosis.