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.

In the last years, molecularly targeted agents and immune based treatments (ITs) have deeply changed the landscape of anti-cancer therapy. Indeed, ITs proved to be very effective in metastatic solid tumors, where outcomes were extremely poor with standard approaches. Such a scenario has been only partially reproduced in hematologic malignancies. In acute myeloid leukemia (AML), as innovative drugs are eagerly awaited in relapsed/refractory setting, different ITs have been explored, but the results are still unsatisfactory. In this work, we will discuss the most important clinical studies to date adopting ITs in AML, providing the bases to understand how this approach, although still in its infancy, may represent a promising therapeutic tool for the next future treatment of AML patients.

Fluorescent semiconductor nanocrystals called quantum dots (QDs) have gained attention in biomedical applications, including imaging, molecular tracking, and drug delivery, due to their unique optical properties. However, their use is limited because of safety issues. This study was aimed at assessment the acute toxicity of QDs with different core chemical compositions and surface charges in mice. In addition, the immunotoxicity of CdSe/ZnS QDs was estimated. CdSe/ZnS, PbS/CdS/ZnS, and CuInS2/ZnS QDs were synthesized and modified with PEG derivatives. The hydrodynamic diameters and surface charges of solubilized QDs were characterized. The QD acute toxicity has been shown to depend on both surface charge and core composition. The immunotoxicity of CdSe/ZnS-PEG-OH QDs in mice was assessed after a single intravenous administration of 0.2 LD100 of the QDs. The QDs have been found to increase the spleen weight and cause spleen, thymus, and bone marrow cell depletion. However, these changes are reversible. A transient increase in the levels of proinflammatory cytokines (MCP1 and IL-6) indicates an acute inflammatory response to a single low dose of QDs. Thus, systemic comparative analysis of QD toxicity has shown how the QD core composition and surface properties affect living organisms.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Abstract: To compare the use of variable mechanical ventilation with conventional mechanical ventilation in porcine model of ARDS. Methods: Animals were divided into two groups (n = 6), conventional ventilation and variable ventilation with bi-oscillatory PEEP. For induction of ARDS, intravenous oleic acid was used until a P/F ratio of 200 to 300 mmHg. The animals were ventilated with pressure control, FiO2 1.0, inspiration-expiration ratio = 1:2, tidal volume 6 ml/kg with the initial respiratory rate adjusted to maintain an end tidal CO2 tension of 35 to 45 mmHg. Variable ventilation was characterized by the oscillation of PEEP from 5 to 10 cmH2O every 4 respiratory cycles, in convencional ventilation group PEEP was set from 5 cmH2O. Ventilatory, hemodynamic parameters, oxidative stress, antioxidant enzymes, Interleukin 8 (IL8) and 17-a (IL17a) and histological analyzes were evaluated; Results: The use of BiPEEP demonstrated improvement in lung compliance and PaO2 in relation to control. The levels of oxidative stress and antioxidant enzymes showed no significant difference. There was no difference in IL17a between groups. In IL8 there was a significant increase in the lung base of control in relation to BiPEEP, and a reduction in the apex of BiPEEP in relation to control. The control group showed changes in lung morphology characterized by cellular infiltrates, a thickening of the alveolar septae and atelectasis, which were attenuated in BiPEEP group; (4) Conclusions: The use of variable ventilation with bi-oscillatory level of PEEP demonstrates a potential ventilatory strategy in an experimental model of ARDS.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be an important therapeutic agent. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to check whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg/dose) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of acute pancreatitis was assessed immediately after the last dose of cerulein, as well as 1, 2, 3, 5, and 10 days after AP induction. Treatment with warfarin dose-dependently increased interna-tional normalized ratio (INR) and attenuated the severity of pancreatitis in histological ex-amination and accelerated pancreatic recovery. Those effects were accompanied with a faster reduction in the pancreatitis-evoked increase in serum activity of amylase and lipase, serum concentration of pro-inflammatory interleukin-1β, and plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg/dose. Conclusion: Administration of warfarin accelerates re-generation of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Acute lymphoblastic leukemia (ALL) is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The treatment of choice for this disease is the enzyme L-asparaginase (ASNase) from bacterial sources. ASNase hydrolyzes circulating L-asparagine in plasma, leading to starvation of leukemic cells. The ASNase formulations of E. coli and E. chrysanthemi present notorious adverse effects, especially the immunogenicity they generate, which undermines both their effectiveness as drugs and patient safety. In this study, we developed a humanized chimeric enzyme from E. coli L-asparaginase, which would reduce the immunological problems associated with current L-asparaginase therapy. For these, the immunogenic epitopes of E. coli L-asparaginase (PDB: 3ECA) were determined and replaced with those of the less immunogenic Homo sapiens asparaginase (PDB:4O0H). The structures were modeled using the Pymol software and the chimeric enzyme was modeled using the SWISS MODEL service. A humanized chimeric enzyme with four subunits similar to the template structure was obtained, and the presence of asparaginase enzymatic activity was predicted by protein-ligand docking.

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

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. Standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSL. Case presentation: A 54-year-old man with a history of gout presented with character change and memory loss. MRI showed a large, enhancing mass spanning the bilateral frontal lobes and right temporal lobe. After endoscopic biopsy, MTX, procarbazine and vincristine (MPV) regimen was initiated for treatment of PCNSL. After initiation of chemotherapy, the patient suffered from a gout attack and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute urid acid nephropathy. Since a good response to chemotherapy was observed, the latter was assumed. After improvement of renal function, MTX was resumed, initiating rasburicase for control of hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after initiation of MTX in PCNSL. For newly diagnosed PCNSL patients with large tumors or hyperuricemia, upfront usage of rasburicase should be considered to prevent it.

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.

Background: Although persistent systemic inflammation is considered to be predictive for future cardiovascular events, it remains unclear whether or not C-reactive protein (CrP) plays an active role in coronary-plaque instability. Here, we report a case of a patient with failed and super-infected renal allograft as a source for systemic inflammation presenting with repeat acute coronary syndromes. Case presentation: A 52-years-old male type-2 diabetic with a failed kidney transplant who was hospitalized for acute urinary-tract infection. In the presence of other, classic cardiovascular risk factors, peak values of CrP coincided with episodes of unstable angina treated by percutaneous coronary interventions. Besides pyelonephritis, the histological examination of the kidney transplant revealed signs of chronic rejection and the presence of a renal cell carcinoma in situ. Once the renal allograft has been removed, systemic inflammation was attenuated, the patient was not re-hospitalized for acute-coronary syndrome within the next 12 months. Conclusion: In this case, systemic inflammation was paralleled by instability of coronary plaques as documented by repeat percutaneous coronary interventions.

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.

Since 1991, there has been an alarming increase in the number of unexplained physiological events (UPEs) reported and experienced by pilots of jet fighters across different fleets. The UPEs have resulted in grounding some airframes, loss of aircraft, and even loss of life. There is no single agreed-upon root cause of UPEs that has been identified, and therefore there is no reliable corrective action. This author analyzed the literature related to other industries where artificial hyperoxic gas mixes are employed and where similar adverse reports have been reported. I hypothesize that UPEs are caused by high-dose oxygen delivery in excess of officially approved oxygen schedules while airflow rates are often inadequate, at a time when the positive pressure breathing feature of their oxygen regulator is not used. In a setting where pulmonary vital capacity is adversely affected by G-maneuvers and oxygen- and G-induced atelectasis, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation, these factors combine to produce respiratory acidosis, followed by acute respiratory distress syndrome, CO₂ narcosis, and coma. 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 our hypothesis.

Objectives: To demonstrate the efficacy of Gemtuzumab ozogamicin in refractory AML patients with organ dysfunctions and poor performance status. Three refractory AML patients with are described. One of them was pretreated by intensive chemotherapy, two other patients progressed during Azacitidine treatment. WHO performance status III . Two patients had respiratory failure grade 2, the other one suffered from acute kidney insufficiency. Two patients were highly febrile with elevated CRP level. Gemtuzumab ozogamicin administration was performed in three patients followed by further switch to Gemtuzumab ozogamicin + Azacitidine or “7+3” treatment. Results: Gemtuzumab ozogamicin administration resulted in abrupt fever cessation in two febrile patients simultaneously with CRP level decrease and fast gradual resolution of respiratory failure. Recovery of kidney function was noticed in patient with renal insufficiency. WHO performance status have elevated in all three patients. No adverse effects grade II-III were noticed. Further treatment made two patients eligible for intensive chemotherapy, one patient was transplanted, patient with kidney failure obtained complete remission. Conclusions: Gemtuzumab ozogamicin therapy appeared to be safe and highly efficacious in relapsed/refractory AML patients with organ dysfunctions and poor performance status.

Background: Acute appendicitis (AA) is the most common cause of emergency surgery. Perforation is more common than adults. Early diagnosis and new markers are needed. The aim of this study was to investigate the effects of plasma Fetuin-A (FA) levels in patients with the acute abdomen (AB). Material and Method: This prospective study included 107 patients younger than 16 years of age who were admitted to the emergency department for abdominal pain between January 2018 and December 2018. The patients who presented to abdominal pain were divided into two groups as AA and other causes (OC) of AB. T Patients with acute appendicitis; intraperitoneal, retrocolic / retrocecal and appendicitis were divided into three groups. Also, the AA group was divided into two groups as perforated appendicitis and non-perforated appendicitis. Serum FA levels of the patients were evaluated in the emergency department. Results: In the AA group, C-reactive protein (CRP) and white blood cell (WBC) levels were higher, and FA levels were significantly lower than in the AB group. Intraperitoneal localization was 95.2% and perforation was frequent. When significant values in the univariate regression analysis for acute abdomen and perforation were compared in the multivariate regression analysis, CRP, WBC, and FA levels were found to be prognostic. Also, decreased FA levels were associated with AA while too much decreased FA levels were associated with the risk of perforation. Conclusion: While trying to diagnose AA in children, the FA level, CRP and WBC may be predictive values to identify risk factors.

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.

Introduction: Cholelithiasis and consumption of alcohol are the most frequent causes of acute pancreatitis (AP), accounting for about 30 to 40% of the cases, respectively. The frequency of acute biliary pancreatitis is high in a certain population in Brazil. Objective: To estimate the global frequencies of acute biliary pancreatitis (ABP), acute alcoholic pancreatitis (AAP) and the cases considered as acute idiopathic pancreatitis (AIP) in studies published from October 2006 to December 31, 2018. Methods: A systematic review of observational studies was performed from October 2006 to December 31, 2018. A meta-analysis by the random effects model was used to calculate the frequencies of global ABP, AIP and AAP and subgroups. Results: Forty-six studies representing 2,341,007 AP cases were included in 36 countries. The overall estimate for acute biliary pancreatitis (ABP) was 41.6% (95% CI 39.2-44.1), followed by acute alcoholic pancreatitis (AAP) with 20.5% (95% CI) 16.6- 24.6) and acute idiopathic pancreatitis (AIP) in 18.3% (95% CI 15.1-27.7). Conclusion: ABP is the most prevalent etiology of AP, being two times more frequent than second-placed pancreatitis. Latin America has a frequency for ABP much higher than the rest of the world. The importance of the etiologic diagnosis is the treatment of the cause for prevention of recurrence.

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.

The clinical outcome for children diagnosed with acute lymphoblastic leukemia is a testimony to the success of modern medicine. Over the past several decades, survival has climbed from ∼ 10% to &gt; 90% for certain subgroups. Yet, the outcome for those with relapsed disease is often poor and survivors struggle with a multitude of healthcare issues, some of which are lifelong. In recent years, the advent of widespread sequencing of tumors has made available previously unrecognized subtypes of leukemia patients who have the potential to benefit from the addition of targeted therapies. Indeed, the promise of precision medicine encompassing a person's environment, genetics and lifestyle is likely to have profound impact on further tailoring therapies that are likely to improve outcomes, diminish toxicity and ultimately pave the pathway for a healthier population.

Introduction. Mexico confirmed its first COVID-19 case in February 2020. Since then, it has been important to describe the presentation and data of critically ill patients with ARDS caused by SARS-CoV-2. Objectives. To determine the survival of critically ill patients with ARDS due to SARS-CoV-2. Secondary objectives are to identify factors associated with mortality in these patients and to evaluate 90-day survival based on these risk factors. Materials and Methods. This observational, retrospective study was conducted in an ICU at a tertiary hospital in Mexico City (March 2020 - March 2023). It included patients over 18 years old with COVID-19 confirmed by PCR, excluding those with negative PCR, those who died within the first 24 hours, or those without invasive mechanical ventilation. Demographic, clinical, and treatment data were collected. Descriptive statistical analyses, logistic regression, and Kaplan-Meier analyses were performed. The study was approved by ethical committees and did not require informed consent. Results. A total of 157 patients with COVID-19 were studied, with a mean age of 62.8 years and a male predominance (74.5%). ARDS was severe in 68.2%, and acute kidney injury (AKI) developed in 70.1%. The mortality rate was 58.6%, with a 90-day survival of 33.1%. Factors such as AKI (OR = 3.4), hemodynamic failure (OR = 6.5), and elevated lactate (OR = 0.201) were independently associated with mortality, with their impact on survival confirmed by the log-rank test. Conclusion. In critically ill patients with ARDS due to COVID-19, the 90-day survival rate was 33.1%. AKI, hemodynamic failure, and elevated lactate were associated with reduced survival, especially when AKI was combined with hemodynamic failure (26.7%).

Usage of novel non-tobacco oral nicotine delivery products (ONDP) has been increasing among adolescents in the United States. It is presumed that they are less toxic than their tobacco containing counterparts, but that has not been examined in controlled studies. Most of the studies have focused on non-renal manifestations of tobacco consumption via different means. The renal manifestations of non-tobacco ONDPs are not very well known, especially in immunocompromised patients. Here, we describe a 19-year-old adolescent with kidney transplant who sustained acute tubular necrosis leading to advanced chronic disease apparently following the usage of non-tobacco ONDP. Further larger studies are needed to study the renal manifestations of these next generation products to raise awareness among public.

Achieving complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undergoing curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong leukemia-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) versus best supportive care (BSC) in elderly AML patients who achieved CR after intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age 71, 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a Variant Allele Frequency (VAF) ≥ 4%. At diagnosis, all patients had 5 to 17 (median 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in 4 patients were linked to a higher relapse risk (HR 4.96, p=0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications.

Diagnosis of encephalitis is a challenging problem due to the heterogeneity of clinical presentations and the myriad of aetiology. The objective was to determine the aetiology, clinical features, laboratory parameters, radiological findings and in-hospital outcome of acute encephalitis syndrome (AES) cases in Myanmar. Methods: A prospective analytic study was conducted at Neuromedical Ward of Yangon General Hospital during March to August 2023. 81 AES cases were enrolled and cerebrospinal fluids (CSF) samples were collected. Qiastat ME Panelwas used to detect viral, bacterial and fungal pathogens. Results: 17 out of 81 (21%) cases were non-encephalitis with alternative definite diagnosis. Among the remaining 64 encephalitis cases, the exact infectious and immune aetiologies were identified in 31/64 (48.4%); 26/31 cases (83.9%) were infectious causes and 5/31 patients (16.1%) were immune encephalitis. Among the infection causes, six Herpes Simplex Virus-1, one bacteriologically confirmed and seven probable Mycobacterium tuberculosis, three Haemophilus influenzae, two Streptococcus pneumoniae, one Streptococcus pyogenes, one Varicella-Zoster Virus (Ramsay Hunt Syndrome with meningoencephalitis), two Cryptococcus neoformans infected patients and rare causes such as Listeria monocytogenes, Burkholdelria cepacia, Sphingomonas paucimobilis and Aspergillus were identified. One case was dual infection with Haemophilus influenzae and Cryptococcus neformans. Abnormal protein levels and CSF pleocytosis were significantly higher among bacterial causes (P<0.05). 6.45% (2/31) of encephalitis patients with identified causes and 12.12% (4/33) of those without organism identified had bad outcome. Conclusions: Herpes encephalitis and tuberculous meningoencepalitis were the commonest. This study highlighted that molecular testing with multidisciplinary approach is required to ensure the right treatment on time.

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Aim: To study the relationship between the location of chest pain (topography) and site of coronary artery involvement in patients of Acute coronary syndrome (ACS) undergoing percutaneous transluminal coronary angioplasty (PTCA). Materials and Method: This observational study analyzed 589 angina topographic sites in 411 consecutive patients hospitalized for Acute Coronary syndrome (ACS) who underwent PTCA at a tertiary care center between January 2017 and December 2019. All parameters including the characteristics and site of the anginal pain, Electrocardiogram (ECG), and Coronary angiography (CAG) findings were recorded and analyzed for their topographical correlation with site of culprit vessel involvement. Result: Out of 411 patients, 337 were Males (82.0%) and 74 (18.0%) were females with 589 topographic sites of angina. The mean age of the study subject was 57.03± 11.28 years. In both ST elevation Myocardial Infarction (STEMI) and Non-ST-elevation Myocardial Infarction (NSTEMI), the Left anterior descending (LAD) was the most affected vessel in 201(63.4%) and 49(53.3%) respectively. The correlation coefficient for LAD occlusion was 0.298 (p=0.001) for the Retrosternal site. The Left Circumflex (LCX) artery showed a positive correlation of 0.647 (p= 0.001) for Jaw with Neck pain and of 0.585 (p=0.001) for Backache with Shoulder pain. The Right Coronary Artery (RCA) showed a positive correlation of 0.713 (p=0.001) for Retrosternal plus Jaw and Neck pain and of 0.719 (p=0.001) for Retrosternal plus Backache. Conclusion: The study reveals a significant correlation between chest pain topography and site of coronary artery involvement. It provides a basis for future research to develop tools that help healthcare professionals quickly identify culprit artery in ACS.

Background The aims of this study were to assess the peri-operative morbidity, mortality and long-term survival of octogenarians undergoing ATAAD repair, and to compare open and closed distal anastomosis techniques. Methods This was a single-centre retrospective study (2007-2021). Open versus closed distal anastomosis were compared. Uni and multi-variable logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Kaplan-Meier and Cox proportional hazards methods were used to compare long-term survival. Results Fifty octogenarians patients were included (median age - 82 years, closed distal – 22, open distal - 28). Median CPB time was 187 minutes (open distal vs closed distal group; 219 minutes vs 115.5 minutes, p30 days or return to theatre; HR; 4.1, p=0.02) predicted adverse survival. Open distal anastomosis did no impact survival. Conclusions – ATAAD repair in selected octogenarians has favourable short and long-term survival. There is no significant difference between open versus closed distal anastomosis strategies.

Polysulfides are endogenously produced in mammals and generally associated with protective functions. Our aim was to investigate the effect of dimethyl trisulfide (DMTS) in a mouse model of acute stress. DMTS activates transient receptor potential ankyrin 1 (TRPA1) channels and leads to neuropeptide release, potentially that of substance P (SP). We hypothesize that DMTS might inhibit the degrading enzymes of endocannabinoids, so this system was also investigated as another possible pathway for mediating the effects of DMTS. Trpa1 gene wild type (WT) and knock out (KO) mice were used to confirm the role of the TRPA1 ion channel in mediating the effects of DMTS. C57BL/6J, NK1 gene KO, and Tac1 gene KO mice were used to evaluate the effect of DMTS on the release and expression of SP. Some C57BL/6J animals were treated with AM251, an inhibitor of the cannabinoid CB1 receptor, to elucidate the role of the endocannabinoid system in these processes. Open field test (OFT) and forced swim test (FST) were performed in each mouse strain. Tail suspension test (TST) was performed in TRPA1 WT and KO animals. C-FOS immunohistochemistry was carried out on TRPA1 WT animals. DMTS treatment increased the number of highly active periods and decreased immobility time in the FST in WT animals, but had no effect on Trpa1 KO mice. DMTS administration induced neuronal activation in stress-related brain areas such as the locus coeruleus, dorsal raphe nucleus, lateral septum, paraventricular nucleus of the thalamus, and paraventricular nucleus of the hypothalamus. DMTS may have a potential role in the regulation of stress-related processes, and the TRPA1 ion channel may also be involved in mediating the effects of DMTS. DMTS can be an ideal candidate for further study as a potential remedy in stress-related disorders.

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.

Mesenteric ischemia diagnosis is challenging with an overall mortality in up to 50% of cases despite advances in treatment. The main problem that affects the outcome is the delayed diagnosis because of non-specific clinical presentation. Multi Detector CT Angiography (MDCTA) is the first line investigation for the suspected diagnosis of vascular abdominal pathologies and is the diagnostic test of choice in suspected mesenteric bowel ischemia. MDCTA can accurately detect the presence of arterial and venous thrombosis, determine the extension and the gastrointestinal tract involved, and provide detailed information determining the subtype and the stage progression of the diseases helping clinicians and surgeons for the proper management. CT can differentiate forms that are still susceptible to pharmacological or interventional treatment (NOM= non-operative management) from advanced disease with transmural necrosis in which a surgical approach is required. Knowledge of CT imaging patterns and corresponding vascular pathways is mandatory in Emergency settings to reach a prompt and accurate diagnosis. The aims of this paper are 1. to provide technical information about the optimal CTA protocol; 2. To empathize the CTA arterial and venous supply to gastrointestinal tract and relative ischemic pattern; 3. To describe vascular, bowel and extraintestinal CT findings for the diagnosis of acute mesenteric ischemia.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

This review was written with the aim of examining the effects that caused an insult such as a wound to an organ such as the skin. Before examining the cellular mechanisms relating to wound healing, the reader is invited to read the structure of the skin as a necessary basis for understand-ing the final aim of this review. The structure of the skin as a basis for understanding the phe-nomena relating to wound healing is addressed taking into account updated literature that ad-dresses the numerous problems of the skin microenvironment. Starting from this awareness, the paragraph dedicated to wound healing becomes complicated when this phenomenon is not im-plemented and therefore the problems dedicated to chronic wounds, keloids and hypertrophic scars are addressed, pathologies that are still difficult to understand and treat today.

Acute and chronic respiratory diseases impose a significant economic and health burden. Distal small airway assessment requires invasive procedures such as a bronchoscopy and bronchoalveolar lavage. The Particles in Exhaled Air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles sized around 0.5-7m and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can measure particle count and mass according to particle size. Subsequent capture of particles in a thin membrane enables application of various analytical methods to assess a broad range of biomolecules including phospholipids, proteins, inflammatory profile, and other metabolites to characterise inflammation and diseases processes such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, lung cancer, and more recently acute infections such as COVID-19. PExA analysis provides a promising alternative to traditional investigative methods in the assessment, diagnosis, and management of respiratory conditions. By evaluating specific biomarkers in the RTLF associated with airway inflammation, PExA may offer a more accurate and comprehensive understanding of the molecular-level changes in the small airways of patients with acute and chronic lung diseases.

In Mexico viticulture represents the second source of employment in the agricultural area after the fruit and vegetable sector. In developed countries, remote sensing is widely used for vineyard monitoring, however, this tool is barely used in developing countries of Iberoamerica. In this re-search, our overall objective is to characterize two vineyards in the state of Queretaro (Mexico) using Sentinel-2 and meteorological data, specifically spectral and thermal indices. Results showed that spectral indices obtained from Sentinel-2 bands have characterized adequately the phenolog-ical evolution of the different varieties of the vineyards. The Modified Soil-Adjusted Vegetation Index (MSAVI) was adequately used to discriminate the first stages of vineyards, while the Nor-malized Difference Vegetation Index (NDVI) was useful to monitor vineyards during the rest stages of vineyards. Thermal indices have shown that the best grape varieties were those that can adapt to both cooler and warmer temperatures, have a reasonable ripening period, and can produce wines with balanced acidity and flavors. In conclusion, the combination of meteorological (including thermal indices) and remote sensing data (NDVI and MSAVI) provide information for choosing the suitable grape variety for this region.

Objective. Acute bowel ischemia is a life-threatening abdominal emergency. In many patients percutaneous endovascular repair of visceral arteries in an antegrade direction, across occluding plaques is challenging and sometimes not possible. Case Report. We present the case of technically successful percutaneous retrograde recanalization of occluded superior mesenteric artery in ctitically-ill 82-year-old patient. The superior mesenteric artery was recanalized via the branches of the celiac trunk; the guidewires were navigated to the target artery through the gastroduodenal and pancreatoduodenal arteries. Conclusion. Retrograde percutaneous recanalization of the superior mesenteric artery is technically feasible, even in hemodynamically unstable patients.

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.

Background and objectives: Although intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS) only a small proportion of stroke patients receive this drug. Low administration rate is mainly due to delayed presentation of patients to the emergency department (ED) or lack of a stroke team/unit in most of the hospitals. So, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors, influence administration of rt-PA we split the general sample (n=202) in two groups: group No rt-PA (n=137) and group rt-PA (n=65) based on performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all sample we found that the median onset-to-ED door time was 180 minutes (IQR, 120-217.5 minutes), door-to-physician time was 4 minutes (IQR, 3-7 minutes), door-to-CT time was 52 minutes (IQR, 48-55 minutes), and door-in-door-out time was 61 minutes (IQR, 59-65 minutes). ED time targets such as door-to physician time (p=0.245), door-to-CT time (p=0.219), door-to-door-out time (p=0.24), or NIHSS at admission to Neurology department (p=0.405), or NIHSS after 24 h (p=0.9) did not have a statistically significant effect on administration or no rt-PA treatment in patients included in our study. Only highest Door-to-CT time was statistically significantly correlated with death outcome. Conclusion: In our study, rt-PA administration rate was higher than expected. Statistically significant correlation between ED time targets was found between lower Onset-to-ED door time with administration of rt-PA treatment (p<0.001) and between highest Door-to-CT time and death outcome.

The global shrimp farming industry is impacted by various infectious diseases, leading to marked production losses. Virulent Vibrio parahaemolyticus strains (VPAHPND) and other Vibrio species cause acute hepatopancreatic necrosis disease (AHPND) in shrimp. We isolated a binary toxin PirA/B-bearing V. campbellii strain (HJ-2023) from a Korean shrimp farm. The biochemical characteristics and antibiotic susceptibility of HJ-2023 were analyzed and compared to those of PirA/B-bearing VPAHPND. Non-AHPND-causing V. campbellii was the control. The pathogenicity of each strain was analyzed in white-leg shrimp. Phylogenetic analysis classified the isolated HJ-2023 strain as V. campbellii. Biochemical tests confirmed distinct properties of HJ-2023, compared to the genetically similar V. harveyi group. The AHPND-causing toxin gene of HJ-2023 showed 100% similarity to the rpoD gene of VCAHPND. An antibiotic disc susceptibility test indicated that HJ-2023 showed resistance to ampicillin, clindamycin, lincomycin, and erythromycin, which is effective against gram-positive bacteria, and showed weak sensitivity to gentamycin. Furthermore, HJ-2023 was 25% less toxic than VPAHPND but could be lethal during aquaculture-related outbreaks. These results highlight the complexity and virulence of AHPND-causing strains through multiple pathways and confirm the pathogenicity of V. campbellii, which increases the risk posed by AHPND to shrimp aquaculture. Our findings could help prevent AHPND.

Background: The aim of this study was to analyze the relationship between breastfeeding duration and adenoid size, snoring and acute otitis media (AOM). Methods: We analyzed the medical history, reported symptoms, ear, nose and throat (ENT) examination, and flexible nasopharyngoscopy examination of 145 children aged 3-5 years. Results: Breastfeeding duration of 3 and 6 months or more had a significant effect on the reduction of snoring (p = 0.021; p = 0.039). However, it had no effect on the adenoid size, mucus coverage and sleeping with an open mouth. Snoring was correlated with open mouth sleeping (p &lt; 0.001), adenoid size with a 75% A/C ratio or more (p &lt; 0.001), and adenoid mucus coverage in the Mucus of Adenoid Scale by Nasopharyngoscopy Assessment - MASNA scale (p = 0.009). Children who were breastfed for less than 3 months had more than a 4-fold greater risk of snoring. There was a statistically significant correlation between AOM and gender (p = 0.033), breastfeeding duration in groups fed 1, 3 or 6 months or more (p = 0.018; p = 0.004; p = 0.004) and those fed with mother’s breast milk 3 or 6 months or more (p = 0.009; p = 0.010). Moreover, a correlation was found between adenoid size and mucus coverage, tympanogram, and open-mouth sleeping (p &lt; 0.001). Independent factors of snoring in 3- to 5-year-old children were breastfeeding duration of less than 3 months (p = 0.032), adenoid size with an A/C ratio of 75% or more (p = 0.023) and open mouth sleeping (p = 0.001). Conclusion: Children breastfed for 3 and 6 months or more exhibited reduced rates of snoring. There was no effect of breastfeeding duration on adenoid size in children aged 3 to 5 years, suggesting that the link between breastfeeding duration and snoring is primarily associated with craniofacial development and muscle tone stimulation. A breastfeeding duration of 1 month or more plays a key role in reducing the rate of AOM. The mother’s milk plays a protective role against AOM. The presence of mucus might be responsible for snoring in preschool children. A medical history of breastfeeding should be taken into consideration when snoring children are suspected of adenoid hypertrophy.

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.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although prognosis continually improved along years, a significant proportion of patients still relapse from the disease due to leukemia resistance to therapy. Methotrexate (MTX), a folic acid antagonist, is a chemotherapy agent commonly used against ALL and a immune-system suppressant for rheumatoid arthritis, that presents multiple and complex mechanisms of action and resistance. Previous studies have shown that MTX modulates the nuclear factor kappa B (NF-κB) pathway, an important family of transcription factors involved in inflammation, immunity, cell survival, and proliferation, frequently hyperactivated in ALL. Using gene set enrichment analysis (GSEA) on publicly available gene expression data from 161 newly diagnosed pediatric ALL patients, we found “TNF-α signaling pathway” to be the most enriched Cancer Hallmark in MTX poor responder patients. Transcriptomic analysis in a panel of ALL cell lines (6 BCP-ALL and 7 T-ALL) also identified the same pathway as differentially enriched among MTX resistant cell lines, as well as in slowly dividing cells. To better understand the crosstalk between NF-κB activity and MTX resistance, we genetically modified the cell lines to express luciferase under a NF-κB biding site promoter. We observed that the fold change in NF-κB activity triggered by TNF-α (but not MTX) treatment correlated with MTX resistance and proliferation across the lines. At the individual gene level, NFKB1 expression was directly associated with a poorer clinical response to MTX, and with both an increased TNF-α-triggered NF-κB activation and MTX resistance in the cell lines. Despite these results, pharmacological inhibition (with BAY 11-7082 and parthenolide) or stimulation (with exogenous TNF-α supplementation) of the NF-κB pathway did not alter MTX resistance of the cell lines significantly, evidencing a complex interplay between MTX and NF-κB in ALL.

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.

Acute ischemic stroke (AIS) is the loss of neurological function due to a sudden reduction in cerebral blood flow and is a leading cause of disability and death worldwide. In recent years, the field of radiological imaging has experienced an explosion that may reach unprecedented heights with the advent of artificial intelligence. One of the latest innovations in artificial intelligence is radiomics, which is based on the fact that a large amount of quantitative data can be extracted from radiological images, from which patterns can be identified and associated with specific pathologies. Since its inception, radiomics has been particularly associated with the field of oncology, with promising results in a wide range of clinical situations. The performance of radiomics in non-tumour pathologies has been increasingly explored in recent years and the results continue to be promising. The aim of this review is to explore the potential applications of radiomics in AIS patients and to theorise how radiomics may change the paradigm for these patients in the coming years.

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.

Background: Acute heart failure (AHF) is a serious medical problem that necessitates hospitalisation and often results in death. Patients hospitalised to the emergency department (ED) should therefore receive an immediate diagnosis and treatment. Unfortunately, there is not yet a fast and accurate laboratory test for identifying AHF. The purpose of this research is to apply the principles of explainable artificial intelligence (XAI) to the analysis of hematological predictors for AHF. Methods: In this retrospective analysis, 425 patients with AHF and 430 healthy individuals served as assessments. Patients' demographic and hematological information was analyzed to determine AHF. Important risk variables for AHF diagnosis were identified using LASSO feature selection. To test the efficacy of the suggested prediction model (XGBoost), a 10-fold cross-validation procedure was implemented. The area under the receiver operating characteristic curve (AUC), F1 score, Brier score, and Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were all computed to evaluate the model's efficacy. Permutation-based analysis and SHAP, were used to assess the importance and influence of the model's incorporated risk factors. Results: White blood cell (WBC), monocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), red cell distribution width-standard deviation (RDW-SD), RDW-coefficient of variation (RDW-CV), and platelet distribution width (PDW) values were significantly higher than the healthy group (p&lt;0.05). On the other hand, erythrocyte, hemoglobin, basophil, lymphocyte, mean platelet volume (MPV), platelet, hematocrit, mean erythrocyte hemoglobin (MCH) and procalcitonin (PCT) values were found to be significantly lower in AHF patients compared to healthy controls (p &lt;0.05). When XGBoost was used in conjunction with LASSO to estimate AHF, the resulting model had an AUC of 87.9%, an F1 score of 87.4%, a Brier score of 0.036, and an F1 score of 87.4%. PDW, age, RDW-SD, and PLT were identified as the most crucial risk factors in differentiating AHF. Conclusions: The XGBoost model demonstrated exceptional performance in accurately estimating Acute Heart Failure, and the application of Explainable Artificial Intelligence effectively provided intuitive explanations for the model's estimations. The suggested interpretable model holds potential for the identification of patients at high risk, thereby facilitating the optimization of treatment and planning for follow-up in cases of AHF.

Purpose: To reassess the results of former meta-analyses focusing on the relationship between novel HES preparations (130/0.4 and 130/0.42) and acute kidney injury. Previous meta-analyses are based on studies referring to partially or fully unpublished data or data from abstracts only. Methods: The studies included in the former meta-analyses were scrutinized by the authors independently. We completed a critical analysis of the literature, including the strengths, weaknesses and modifiers of the studies when assessing products, formulations and outcomes. Results: Both the published large studies and meta-analyses show significant bias in the context of the deleterious effect of 6% 130/0.4-0.42 HES. Without (1) detailed hemodynamic data, (2) the exclusion of other nephrotoxic events and (3) a properly performed evaluation of the dose-effect relationship; the AKI-inducing property of 6% HES 130/0.4 or 0.42 could not be accounted as evidence. The administration of HES is safe and effective if the recommended dose is respected. Conclusion: Our review suggests that there is questionable evidence for the deteriorating renal effect of these products. Further well-designed, randomized and controlled trials are needed. Further conclusions formulated for resource-rich environments should not be extended to more resource-scarce environments without proper qualifiers provided.

Abstract Background: Most cardiac metastases emerge from primary lung, breast, and hematologic malignancies. The clinical manifestations of cardiac metastasis vary depending on tumor location and size. Cardiac metastasis from cervical squamous cell carcinoma is extremely rare and is mostly found on autopsy. We report a case of cervical cancer metastasis to the interventricular septum. Case Summary. This report discusses the case of a 48-year-old woman with interventricular septal metastases, originating from squamous cell carcinoma of the cervix. The woman came to our hospital after experiencing a fainting spell. Her hospital stay was notable for a brief syncopal event during a 30-second asystole episode, which ended spontaneously. Upon awakening, she reported severe chest pain. In response, she was quickly taken to the catheterization laboratory. There, a coronary angiography revealed an 80% blockage in her left anterior descending artery. Two years prior, our patient was diagnosed with invasive squamous cell cervical carcinoma with PET/CT showing no evidence of metastatic disease. A repeat PET/CT scan was done following cardiac catheterization and was significant for a mass along the interventricular septum of the heart. Discussion. Cardiac metastasis from primary cervical squamous cell carcinomas is scarcely reported in medical literature. Among these rare cases, the majority involved the right ventricle, with only three involving the left ventricle. There are no documented instances of metastasis to the interventricular septum. To our knowledge, this would be the first such case.

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.

Relapsed acute lymphoblastic leukemia (ALL) represents a continuous challenge for the clinician. Despite recent advances in treatment, the risk of relapse remains significant. The clinical, biological, cytogenetic, and molecular characteristics may be different at the time of relapse. Current comprehensive genome sequencing studies suggest that most relapsed patients, especially those with late relapses, acquire new genetic abnormalities, usually within a minor clone that emerges after ALL diagnosis. We report the case of a 23-year-old young woman diagnosed with Philadelphia chromosome negative B-cell acute lymphoblastic leukemia. The patient underwent allogeneic stem cell transplantation (allo-HSCT) after complete remission. Although having favorable prognostic factors at diagnosis, the disease relapsed early after allo-HSCT. The cytogenetic and molecular exam at relapse was positive for the Philadelphia chromosome, respectively for the bcr-abl transcript. What exactly led to the relapse of this disease in a more aggressive cytogenetic and molecular form, although there were no predictive elements in the diagnosis of this relapse?

The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

The emergence of acute, severe non hepA–E hepatitis of unknown etiology (ASHUE) has attracted global concern owing to the very young age of the patients and its unknown etiology. Although this condition has been linked to several possible causes, including viral infection, drugs, and/or toxin exposure, the exact cause remains unknown; this makes treatment recommendations very difficult. In this review, we summarize recent updates on the clinical manifestations, complemented with laboratory results, case numbers with the global distribution and other epidemiological characteristics, and the possible etiologies. We also provide the proposed actions that could be undertaken to control and prevent further spread of this hepatitis. Since many etiological and pathological aspects of the acute non hepA–E hepatitis remain unclear, further research is needed to minimize the severe impact of this disease.

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.

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) was the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed after ethical approval by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different time points after the start of treatment was demonstrated as well. The age (mean±SD) of the 53 patients (44.7±17.0) and 39 controls (49.3±15.9) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p&lt;0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patient’s self-diagnosis of AC and as a PRO measure tool.

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 current research investigated the environmental risk of the polycyclic musk compounds, Galaxolide® (HHCB) and Tonalide® (AHTN), in the marine environments. These substances are lipophilic, bioaccumulated and potentially biomagnified in aquatic organisms. To understand the toxicity of HHCB and AHTN, we performed acute toxicity tests by exposing marine microalgae (Phaeodactylum tricornutum, Tretraselmis chuii and Isochrysis galbana), crustaceans (Artemia franciscana), echinoderms (Paracentrotus lividus), bivalves (Mytilus galloprovincialis), fish (Sparus aurata) and a candidate freshwater microalga (Raphidocelis subcapitata) to environmentally relevant concentrations (0.005 - 5 µg/L) following standardized protocols. The effects of both substances on microalgae growth were incipient and only I. galbana was sensitive to HHCB and AHTN, with IC10 values of 5.22 µg/L and 0.328 µg/L, respectively. Significant (p < 0.01) concentration dependent responses were measured in P. lividus and M. galloprovincialis larvae developments as well as S. aurata mortality tested with HHCB. The effect of HHCB on P. lividus larvae development was the most sensitive endpoint recorded, producing an EC50 value of 4.07 µg/L. Our results show that HHCB represents a high risk to P. lividus larvae development for early life stages in marine environments.

Purpose: To report the early clinical outcomes of combining intensity‐modulated radiation therapy (IMRT) and intensity‐modulated proton therapy (IMPT) in comparison with IMRT alone in treating the oropharynx cancer (OPC) patients. Materials and Methods: The medical records of 148 OPC patients were retrospectively reviewed, who underwent definitive radiotherapy (RT) with concurrent systemic therapy, from January 2016 till December 2019 at Samsung Medical Center. During the 5.5 weeks’ RT course, the initial 16 (or 18) fractions were delivered by IMRT in all patients, and the subsequent 12 (or 10) fractions were either by IMRT in 81 patients (IMRT only) or by IMPT in 67 (IMRT/IMPT combination), respectively, based on comparison of adaptive re-plan profiles and availability of equipment. Propensity‐score matching (PSM) was done on 76 patients (38 from each group) for comparative analyses. Results: With the median follow‐up of 24.7 months, there was no significant difference in overall survival and progression free survival between groups, both before and after PSM. Before PSM, IMRT/IMPT combination group experienced grade ≥3 acute toxicities less frequently: mucositis in 37.0% and 13.4% (p<0.001); and analgesic quantification algorithm (AQA) in 37.0% and 19.4% (p=0.019), respectively. The same trends were observed after PSM: mucositis in 39.5% and 15.8% (p=0.021); and AQA in 47.4% and 21.1% (p=0.016), respectively. In multivariate logistic regression, grade ≥3 mucositis was significantly less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.027 and 0.024, respectively). AQA score ≥3 was also less frequent in IMRT/IMPT combination group, both before and after PSM (p=0.085 and 0.018, respectively). Conclusions: In treating the OPC patients, with comparable early oncologic outcomes, more favorable acute toxicity profiles were achieved following IMRT/IMPT combination than IMRT alone.

Migraine is one of the leading causes of disability worldwide [1,2]and patients with acute migraine frequently present to emergency departments (ED)[3]. The current literature suggests that ED treatment of migraine headache varies across institutions [4-7]. Considering this, we conducted a scoping review to summarize trends in medication prescribing patterns for acute migraine treatment in the ED setting. Trends were evaluated for factors influencing treatment choices, with particular attention placed on opioids and migraine specific therapy. This scoping review was based on the Arksey and O'Malley methodological framework[8]and included studies published between 1 January 2000 until 31 May 2020. 14 publications met the inclusion criteria. The most common classes of medication prescribed were often anti-emetics or Non-steroidal anti-inflammatory drugs (NSAID), but rates varied between studies. There was a concerning trend towards an underutilization of triptans and overutilization of opiates. The use of specific clinical goals of treatment (e.g. two-hour pain free freedom response) was also not evident. Additionally, 88% (n=8) of the 9 studies commenting on adherence to hospital or evidence-based guidelines stated that practices were non-adherent. Overall, the reviewed literature reveals treatment practices for acute migraine in the ED are heterogeneous and deviate from established international recommendations.

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

Aim: Aim of our study to evaluate various factors responsible for surgical site infection after gastrointestinal and hepatobiliary surgeries. Material and Methods: Patient who underwent gastrointestinal and hepatobiliary surgery in our department were evaluated retrospectively. Various factors associated with surgical site infection were evaluated using univariate and multivariate analysis. Surgical site infection was defined as any culture positive discharge from the wound within 30 days of surgery.Statistical analysis was done using SPSS version 23. Results: We evaluated total 331 patients operated between April 2018 to March 2020. 14 patients were lost to follow up after discharge and before completing post operative day 30. 18 patients expired before 30 days without developing SSI and were excluded from the study as per exclusion criteria. 299 patient included in the study. Total 20 patients developed surgical site infection. It showed SSI rate in our study population was 6.68%. On univariate analysis prolonged hospital stay, more blood product used, higher cdc grade of surgery, higher ASA grade, more operative time, open surgeries,colorectal and HPB surgeries were associated with surgical site infections. On multivariate analysis only prolonged hospital stay independently predicted Surgical Site Infectins. (p=0.014,0dds ratio 1.223, 95% confidence interal 1.042-1.435). Conclusion: Prolonged hospital stay independently predicts surgical site infections after gastrointestinal and hepatobiliary surgery.

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.

Athletes are exposed to high-intensity loads to promote athletic performance, however without appropriate evaluation for its effects. This study investigates the effects of four types of exhaustion exercises on Heart Rate Variability (HRV) and Poincaré features as markers of central fatigue; Creatine Kinase (CK) and blood lactate concentrations ([LA-]b) as biomarkers of peripheral fatigue. To achieve this purpose, ten healthy volunteers were exposed to exhaustive exercise using isotonic-, isometric-, aerobic-, and anaerobic-fatigue protocols. HRV Poincaré features, standard deviation of instantaneous beat-to-beat R-R interval variability (SD1) and standard deviation of continuous long-term R-R interval variability (SD2) variables were collected. Central fatigue was tested through the sympathetic stress index (SS) and the sympathetic and parasympathetic index (SS/SD1). Blood samples were collected at the beginning and at the end of the exercises to determine CK and [LA-]b. The SD1 decreased in each exercise protocol, while the SS and SS/SD1 increased. [LA-]b and CK increased at the end of each protocol and correlated with SD1 and SS/SD1. HRV, CK, and [LA^-]_b are acute markers to detect, both central and peripheral fatigue; sensitive to the type, duration, and intensity of exercise, being HRV a novel noninvasive marker, simple and useful for sports coaches and athletes.

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.

: This Systematic Review focused on the use of Bifidobacterium infantis and Bifidobacterium breve in neurodegenerative diseases. The study of metabolomics has demonstrated the relationship between dysbiosis and neuronal death. The modulation of the gut microbiota in the intervention of these pathologies has become a promising area of study, showing beneficial results such as the improvement of synaptic function, the reduction of neuroinflammation, as well as the improvement of associated neuropsychiatric symptoms. Several studies have addressed the administration of Bifidobacterium infantis and Bifidobacterium breve, alone, in conjunction or in combination with other strains, in the intervention of neurodegenerative diseases. This Systematic Review includes the results of 17 research articles (n=5 in humans and n=12 in animal models) and the main result was that the use of these Bifidobacterium strains, alone, in conjunction or in combination with other strains, produced improvements in neurodegenerative disease-related symptomatology and degenerative cellular processes. However, some studies shown neutral results in certain variables. These data suggest that the use of these probiotics has a neuroprotective effect that may delay the progression of the disease. This research provides relevant and updated information on the use of these Bifidobacterium strains in neurodegenerative pathologies such as Alzheimer's disease and Parkinson's disease.

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.

Acute pancreatitis (AP) is a potentially fatal organ disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that generating urate and also responsible to produce reactive oxygen species (ROS). Considerable clinical and mechanical research has been conducted over many decades to explore the function of XO in AP and its promising therapeutic applications. Unquestionably, XO is a key part of starting and progressing AP by ROS production. Not fully known, though, are XO's many other functions besides ROS resource in both local and global processes, such as its role in cellular signaling or metabolism regulation. This review seeks to summarize the function of XO in AP pathophysiology by analyzing the inherent biological and chemical properties of XO, and lastly provide fresh concepts for future research.

Background/Objectives: Pulmonary diseases are common in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). Although high prevalences of chronic obstructive pulmonary disease and lung cancer (LC) are known, the prevalence of these and other pulmonary diseases regarding their relation to outcome of TAA and/or AAA are not determined. Methods: Pulmonary diseases present at aortic aneurysm (AA) diagnosis and follow-up periods and cause of death of 952 patients with TAA, AAA, or TAA+AAA (including thoracoabdominal AA) treated at our institution in Japan, were retrospectively analyzed. Cox regression analysis was used to investigate potential risk factors of mortality. Results: Mean patient age was 72.4 years, and median follow-up was 4.92 years. At diagnosis, 528 (55.5%) patients had pulmonary diseases, including emphysema without interstitial lung disease (ILD) or LC, LC, idiopathic pulmonary fibrosis (IPF) without LC, non-IPF ILD without LC, and interstitial lung abnormalities (ILAs) without LC in 250, 85, 65, 15, and 58 patients, respectively. During follow-up, LC and acute exacerbation (AE) of IPF developed in 50 and 12 patients, respectively. In 213 patients who died, there were 45 (21.1%) aortic disease-related deaths. Other causes of death included LC (27.7%), cardiovascular event (9.4%), pneumonia (5.6%), and interstitial lung disease (4.7%). In a multivariate Cox regression hazard model, age, larger maximum aneurysm diameter, and coexisting LC, IPF, or concomitant cancer were associated with poor prognosis. Conclusions: In patients with AA, not only age and aneurysm diameter but also coexisting LC and IPF were prognostic factors for mortality.

The expression of the oncogene zinc-finger protein 217 (ZNF217) has been reported to play a central role in cancer development, resistance, and recurrence. Therefore, targeting ZNF217 has been proposed as a possible strategy to fight cancer, making necessary to discover novel com-pounds. The present work aims to characterize the chemopreventive properties of cucurbitacin D , a compound with a broad range of anticancer effectsin relation to the ZNF217 expression. Different cucurbitacins were isolated from the Vietnamese plant Elaeocarpus hainanensis. The purified compounds were tested on nucleophosmin-mutated acute myeloid leukemia and other hematology cancer to study their effects on viability, apoptosis, cell cycle and on the expression of ZNF217. Cucurbitacin D reduced the number of acute myeloid leukemia cells by increasing apoptosis and blocking cell cycle progression. It also significantly decreased ZNF217 expression but only in the OCI-AML3 Nucleophosmin-mutated cell line, but not in other hematologic cancers. The reduction in ZNF217 expression contributed significantly to the blocking of cell cycle progression but not to apoptosis as established by the silencing of the same gene. The obtained results suggest Cucurbitacin D as a promising molecule to target the mutated Nu-cleophosmin or its pathway in acute myeloid leukemia cells, although further studies are needed for in depth investigatiion of its specificity.

The issue of climate change represents a significant global risk that demands immediate attention. However, higher education frequently fails to incorporate global perspectives and intricate transdisciplinary matters. In order to integrate global and transdisciplinary aspects into the curriculum of a technical university with a focus on computer science, a Master's programme has been developed. The programme's objective is to situate global risk at the core of the curriculum, thereby encouraging scientists to work beyond the boundaries of their respective disciplines. The paper considers the challenges that science and higher education must address to facilitate pathways towards a peaceful and sustainable future. It argues for a shift in focus from short-term and localised issues to a more holistic approach, emphasising the importance of considering universal problems. The curriculum, as developed, may be regarded as a guide for future university efforts in the fields of global risk and climate change.

Objectives: Recently, desert dust in Europe has been recognized as a cardiovascular health problem. In Spain, desert dust inflows in recent years have been associated with worsening air quality. The present study examines whether desert dust events are related to the incidence of acute coronary syndrome (ACS) in patients under 55 years of age. Methods: Data from 2416 consecutive patients admitted to a tertiary hospital due to ACS were prospectively analyzed. A case-crossover time-stratified design using Poisson conditional regression models was applied to estimate the impact of desert dust events involving particulate matter concentrations of aerodynamic diameter < 10 μm (PM10) on the incidence of ACS. Results: Desert dust intrusion on days 0 to 5 after ACS onset showed no significant association with the incidence of ACS in patients under 55 years of age. The incidence rate ratios of PM10 concentrations 1, 2, 3, 3, 4 and 5 days before ACS onset (for changes of 10 µg/m3) were 1.02 (95% CI 0.97-1.1; p = 0.41), 1.01 (95% CI 0.96-1.07; p = 0.66), 0.99 (95% CI 0.94-1.05; p = 0.78), 0.96 (95% CI 0.9-1.02; p = 0.18) and 0.97 (95% CI 0.91-1.04; p = 0.41). Conclusions: Our findings suggest that desert dust is unlikely to be related to the incidence of premature coronary heart disease.

Applying the iterative methodology for dimensionality reduction/feature selection using categorical gradient boosted trees, as it has been defined in and has been successfully applied on similar datasets in and , on a dataset consisted of 12708 gene expressions coming from 5052 individuals from 105 studies, we classify whether a person has acute myeloid leukaemia (AML) or is healthy. A CatBoost model on a dataset with reduced dimensions of 72 genes reached a ROC-AUC score of 0.9973 using ten fold cross validation (10CV) and ROC-AUC: 0.9988 on an inference dataset. We further investigate the options of using less genes that potentially could be used in clinical practise and genes than have not been associated to AML yet, or to blood cancer in general. On the same folds of the 10CV and on the same inference dataset the performance of the tuned CatBoost models show that it could be the case that not all genes with an association to AML have been found yet and 19 genes could be enough to predict AML: CatBoost63 (ROC-AUC: 0.9941, Test: 0.9942), CatBoost19: (ROC-AUC: 0.9946, Test: 0.9941) and CatBoost15: (ROC-AUC: 0.9922, Test: 0.9900). In addition, our results verify that a gene diagnostic test for AML could be possible in the future as well as further research is needed on these 15 genes that it could lead to new and better drugs.

Ischemic heart disease is the leading cause of mortality worldwide. There is evidence of the participation of Aβ in thrombosis and clinical manifestations of acute coronary syndromes. In this study, we investigated the correlation of Aβ peptides with myocardial injury and inflammation biomarkers in acute coronary syndrome. This is a single-center, cross-sectional, observational, and correlation study that included 65 patients within the first 12 hours after symptom onset (chest pain, shoulder pain, or chest discomfort) with ST-elevation and non-ST elevation myocardial infarction who were admitted in the Coronary Care Unit, biochemical parameters of Aβ peptides levels were evaluated. Our results show that NSTEMI patients had a higher prevalence of hypertension, diabetes, smoking, and prior myocardial infarction when compared to STEMI patients. We observed a higher level of Aβ-42 in NSTEMI, but no difference in Aβ-40 levels. We also found a correlation between age and NT-proBNP with both Aβ peptides (Aβ-40, Aβ-42) in both groups. In this analysis, NSTEMI patients had higher prevalence of cardiovascular risk factors. Considering the toxic properties of Aβ-42 in coronary endothelial cells and cardiomyocytes, this peptide may be useful in risk stratification scores in patients with NSTEMI.

Urinary tract infections (UTIs) are among the most common bacterial infections in community and hospital settings. Infections of the urinary system can range from pyelonephritis to urethritis. Acute renal infections encompass entities such as acute pyelonephritis, acute focal bacterial nephritis, renal and perinephric abscesses, emphysematous pyelonephritis, and pyonephrosis,while xanthogranulomatous pyelonephritis is a chronic granulomatous inflammatory condition that affects the kidneys. The diagnosis of UTIs predominantly relies on clinical assessment and confirmation through abnormal laboratory results. Therefore, routine medical imaging is typically reserved for complicated cases, aiming to identify contributing factors such as renal calculi, determine the type of infection, and evaluate the extent of the infection and its associated complications. Furthermore, imaging has become crucial for radiologists during interventional procedures in the treatment of pyonephrosis and renal abscesses. Traditional imaging tools, like abdominal X-rays, are vital for identifying renal calculi and gas shadows in emphysematous pyelonephritis, while ultrasonography emerges as an excellent modality for assessing urinary infections in emergency scenarios, pregnancy, and paediatric cases. Contrast-enhanced computed tomography (CECT) or non-contrast computed tomography (NCCT) is the imaging method of choice in the most complex situations, allowing for precise assessment of the disease burden. Current MRI sequences yield promising results in specific scenarios, such as pregnancy and paediatric subjects, where minimising radiation exposure is a concern. This article focuses on elucidating the essential radiological modalities and their distinctive features in the context of renal infections, offering valuable guidance to microbiologists and physicians.

Mesoporous silica nanoparticles (MSNs) can be used as carrier materials for the controlled release of pesticides while reducing their negative environmental impact. In this study, we screened an active ingredient, p-cymene (PC), with an excellent inhibitory effect on rice bacterial blight. Subsequently, the PC was successfully loaded onto MSNs via physisorption(PC@MSNs). PC@MSNs, characterized by a regular spherical shape, smooth surface, and an MSN average size of 262.9 nm, achieved an 8.6 % drug loading capacity. The release kinetics of the PC from the PC@MSNs demonstrated a sustained release (288 h) pattern influenced by drug diffusion. The efficacy of the PC@MSNs against Xanthomonas oryzae pv. Oryzae paralleled those of PC. Acute toxicity assays re-vealed that the PC@MSNs were less toxic to aquatic life (LC50=257.867 mg/L) and that the formu-lation showed no adverse effects on rice seedling growth. In summary, these results suggest that PC@MSNs can broaden PC's application scope in managing rice diseases.

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.

Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent, however other viruses can be the reason of the disease. We retrospectively reviewed the clinical features of infants aged less than 12 months referred to our Pediatric Units of Chivasso, Cirié and Ivrea for acute bronchiolitis requiring hospitalization over two consecutive bronchiolitis seasons. Patient-, disease- and treatment related variables were analyzed in this retrospective study. We were able to show how with the high flow oxygen support (HFNC) only a very low number of children (8 out of 192) need to be trasferred to our HUB referral centers. The probability of success were 96% for all patients and 93% for RSV vs. 98% for non-RSV patients (P=NS). Factor associated to failure of treatment were age below 1 months and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved management of bronchiolitis in Spoke hospitals, reducing transfer to a Hub hospital provided with Intensive Care Units.

Endovascular therapy (EVT) has revolutionized the management of acute ischaemic strokes with large vessel occlusion, with emerging evidence suggesting its benefit also in large infarct core volume strokes. In the last 2 years, 4 randomised controlled trials have been published on this topic - RES-CUE-Japan-LIMIT, ANGEL-ASPECT, SELECT2 and TENSION, with overall results showing that EVT improves functional and neurological outcomes compared to medical management alone. This review seeks to summarise the recent evidence presented by these 4 trials and highlight some of the limitations of our current understanding on this topic.

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 and Objectives: The severity of acute pancreatitis (AP) is graded as mild (MAP), moderately severe (MSAP), and severe (SAP) according to the revised Atlanta Classification. Determining the severity of AP is the main goal in the early time of AP. The aim of this study was to compare laboratory parameters or indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-creatinine index (NCI) at admission for predicting severity of AP. Materials and Methods: In this retrospective study, the data from patients who admitted with diagnosis of AP between January 2018 and December 2021 were collected. Laboratory parameters and indices including NLR, PLR and NCI were compared in the discrimination of AP severity groups. Results: A total of 421 patients [MAP group (n=213), MSAP group (n=158) and SAP group (n=50)] were included. WBC count, neutrophil count, hematocrit, CRP, BUN, creatinine, NLR and NCI were significant parameters to discriminate AP subgroups. The AUROC analysis for discriminating MSAP from MAP showed that WBC (AUC: 0.723, 95% CI: 0.674-0.768, p&lt;0.001), hematocrit (AUC: 0.566, 95% CI: 0.514-0.607, p=0.032), NLR (AUC: 0.649, 95% CI: 0.598-0.698, p&lt; 0.001) and NCI (AUC: 0.749, 95% CI: 0.701-0.792, p&lt;0.001) were statistically significant parameters. Similarly, AUCs to discriminate SAP from MSAP were (AUC: 0.649, 95% CI: 0.579-0.713, p &lt; 0.001) for WBC, (AUC: 0.703, 95% CI: 0.621-0.785, p&lt; 0.001) for BUN, (AUC: 0.602, 95% CI: 0.532-0.669, p=0.029) for CRP and (AUC: 0.742, 95% CI: 0.676-0.800, p&lt;0.001) for NCI. Logistic regression analyses indicated that NCI was the only parameter to discriminate MSAP form MAP (OR: 1.119, 95% CI: 1.015-1.235, p=0.023) and SAP from MSAP (OR: 1.113, 95% CI: 1.042-1.888, p = 0.001). Conclusions: The present study enabled the identification of neutrophil-creatinine index as a new prognostic tool for the assessment AP severity at hospital admission.

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.

The discovery of microRNAs and their role in disease today represents a substantial breakthrough that has inspired and propagating research on microRNAs as targets for diagnosis and therapy. Cardiovascular disease is an area where the limitations of early diagnosis and conventional pharmacotherapy are evident and deserve attention. Thus microRNA-based drugs have substantial potential for development. Research and its application can progress considerably as witnessed in preclinical and clinical trials. The use of miRNAs remains experimental at the time of writing but has a promising role in the diagnosis and prognosis of a variety of acute coronary syndrome presentations. Its use, alone or in combination with currently available biomarkers, could be adopted soon, especially if diagnostic ambiguity exists. In this review, we explore the current state of knowledge about microRNAs as potential targets for diagnosis and therapy in the cardiovascular system. We report recent improvements in the acknowledgment and characterization of microRNAs focusing on clinical translation. The new dares and outlooks toward clinical application are discussed.

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.

Purpose: Oxidative stress is responsible for over seventy five diseases and other harmful cytological challenges including cancer, type 2 diabetes mellitus, lipid peroxidation, distortion of cell membrane integrity, shortening of telomerase among others. Antioxidant potency of any plant is a very positive remedy to the debilitating effects of prooxidants and oxidants. The study was aimed at investigating the antioxidant potency of methanol extract of Pentaclethra macrophylla stem bark- in vitro and in vivo. Methods: Different phytochemicals were determined using standard methods. Nitric oxide, 1, 1-diphenyl-2- picrylhydrazyl (DPPH) radical scavenging activity, total antioxidant capacity and ferric reducing/anti-radical power were used to investigate the in vitro antioxidant activity. Catalase assay, superoxide dismutase, malondialdehyde and glutathione peroxidase were used to determine the in vivo antioxidant efficacy using six groups of five rats. Results: The result showed various quantities of phytochemicals, including antioxidant phytochemicals-flavonoids, tannins and total phenolics. The in vitro assay showed that 250 μg/ml of extract had the highest percentage inhibition of DPPH radical (93.93%). The 125 μg/ml had the highest scavenging activity of nitric oxide radical (49.47%) while 250μg/ml showed the least with 41.73%. Other methods showed various degrees of activity. The in vivo antioxidant showed that the principal mechanism of antioxidant activity is by modulating the iron-dependent catalase activity. Conclusion: Pentaclethra macrophylla has both in vitro and in vivo antioxidant activities and therefore is useful in ameliorating the debilitating effects of oxidants.

Objectives: The aim of this study is to evaluate some mechanisms of the immune response of people infected with SARS-CoV-2 in both acute infection and early and late convalescence phases. Methods: This is a cohort study of 70 cases of COVID-19, confirmed by RT-PCR, followed up to 60 days. Plasma Samples and clinical data were. Viral load, blood count, indicators inflammation were the parameters evaluated. Cellular immune response was evaluated by flow cytometry and Luminex immunoassays. Results: In the severe group, hypertension was the only reported comorbidity. Non severe patients have activated memory naive CD4+ T cells. Critically ill patients have central memory CD4+ T cell activation. Severe COVIS-19 patients have both central memory TCD8+ T cells and activated effector TCD8+ cells. Non-severe COVID-19 cases showed an increase in IL1β, IL-6, IL-10 and TNF and severely ill patients had higher levels of the cytokines IL-6, IL-10 and CXCL8.Conclusion: The present work showed that different cellular responses are observed according to the COVID-19 severity in patients from Brazil an epicenter the pandemic in South America. Also, we notice that some cytokines can be used as predictive markers for the disease outcome, possibility implementation of strategies effective by health managers.

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.

The traditionally dismal outcome of acute myeloid leukemia (AML) patients carrying the FMS-related tyrosine kinase 3 (FLT3) mutations has been mitigated by the recent introduction into the clinics of tyrosine kinase inhibitors (TKI) such as midostaurin and gilteritinib. The present work summarizes the clinical data that led to the use of gilteritinib in clinical practice. Gilteritinib is a 2nd generation TKI with deeper single-agent activity than 1st generation drugs against both FLT3-ITD and TKD mutations, in human studies. Moreover, the phase I/II dose-escalation, dose-expansion Chrysalis trial showed an acceptable safety profile of gilteritinib (diarrhea, elevated aspartate aminotransferase, febrile neutropenia, anemia, thrombocytopenia, sepsis, and pneumonia) and a 49% overall response rate (ORR) in 191 FLT3-mutated relapsed/refractory (R/R) AML patients. In 2019, the pivotal ADMIRAL trial showed that the median overall survival was significantly longer in patients treated with gilteritinib than among those receiving chemotherapy (9.3 vs 5.6 months, respectively) and the ORR to gilteritinib was 67.6%, outperforming the 25.8% for chemotherapy arm and leading to the license for its clinical use by the US Food and Drug Administration. Since then, several real-world experiences confirmed the positive results in the R/R AML setting. Finally, gilterinib based combinations currently under investigation with several compounds (venetoclax, azacitidine, conventional chemotherapy, etc.) and some practical tips (maintenance after allogeneic transplantation, interaction with antifungal drugs, extramedullary disease, and onset of resistance) will be analyzed in detail in the review.

Abstract: Background: Trauma is the leading cause of morbidity and mortality in young patients, acute surgical conditions cause morbidity and mortality in patients of all ages. Computed tomography scan (CT) assist greatly in the investigation and management of these patients with blunt and penetrating trauma, facilitating early diagnosis and expedites early appropriate treatment of these patients. Acute non-traumatic surgical conditions also mimic non-surgical pathologies and differentiating the two is important because management is different and any delay in surgical intervention results in high morbidity and some may even result in mortality. Method: Literature review of the role of multidetector CT scan (MDCT) in managing acute surgical emergencies and trauma-diagnosis in the trauma patient and patients presenting with acute surgical emergencies. The focus is on the role of the MDCT in the management of these patients. Results highlight that the use of MDCT expedites management of these patients, allowing early surgical intervention and preventing unnecessary surgical interventions where the intervention is not indicated, based on the MDCT results. Conclusion: This paper emphasizes the important role that is played by the MDCT in the management of the above patients.

Background: Primary infection has been questioned as the pathogenetic cause of acute appendicitis. We attempted to identify the bacteria involved, and to investigate if their species, types, or combinations affected the severity of acute appendicitis in children. Methods: Samples from both the appendiceal lumen and the peritoneal cavity of 72 children who underwent appendectomy were collected to perform bacterial culture analysis. The outcomes were studied to see if and how they were associated with the severity of the disease. Regression analysis was performed to identify any risk factors associated with complicated appendicitis. Results: Escherichia coli, Pseudomonas aeruginosa and Streptococcus species were the most common pathogens found in the study population. The same microorganisms, either combined or separate, were the most common in the appendiceal lumen and the peritoneal cavity of patients with complicated appendicitis. Gram-negative bacteria, polymicrobial cultures in the peritoneal fluid and in the appendiceal lumen, were associated with complicated appendicitis. Polymicrobial cultures in the peritoneal cavity presented four times higher risk of complicated appendicitis. Conclusion: Polymicrobial presentation and gram-negative bacteria are associated with complicated appendicitis. Antibiotic regimens should target the combinations of the most frequently identified pathogens, speculating the value of early antipseudomonal intervention.

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.

Introduction: CT perfusion (CTP) is an alternative tool to assess cerebral hemodynamics in brain trauma. As traumatic acute subdural hematomas (ASH) are severe lesions commonly associated with poor outcome, we aimed to evaluate the brain hemodynamics in this population. Methods: Five patients admitted at the emergency department sustaining traumatic acute subdural hematoma were evaluated. Preoperative CTP was performed immediately after nonenhanced head CT scan. Postoperative CTP was performed in four patients. The outcome was assessed 6 months after surgery using the extended Glasgow Outcome Scale. Results: 4 male and 1 female were evaluated. Mean age was 46y (SD: 8.1). Mean preoperative midline brain shift was 10.1 mm (SD: 1.8). The main mechanism of trauma was falling (four patients). There was a general improvement in cerebral blood flow (CBF) after surgery from 23.9 (SD: 6.1) to 30.7 ml/100g/min, (SD: 5.1) and in mean transit time (MTT) from 7.3 (SD: 1.3) to 5.8s (SD:1.0), although it is not statistically significant (p=0.06 and p=0.06, respectively). There was still a reduction in the cerebral blood volume (CBV) media when compared to the value after surgery, from 2.63 (SD: 1.10) to 2.34 ml/100g (SD: 0.67), which is not statistically significant (p=0.31). Spearman correlation test of postoperative and preoperative CBF ratio with outcome was 0.94 (p=0.054). Only one patient died (three days after surgery). This patient was victim of car crash and had the highest preoperative MTT (9.97 seconds) and CBV (4.51 ml/100 g). Conclusion: Post-operative improvement of hemodynamic CTP parameters may be correlated with outcomes after ASH. Further studies with larger samples are required to confirm this hypothesis.

Searching for bioactive compounds within the huge chemical space is like trying to find a needle in a haystack. Isatin is a unique natural compound which is endowed with different biopertinent activities specially in cancer therapy. Herein, we envisaged that adopting a hybrid strategy of isatin and α,β-unsaturated ketone would afford new chemical entities with strong chemotherapeutic potential. Of interest, compounds 5b and 5g demonstrated significant antiproliferative activities against different cancer genotypes according to NCI assay. Concomitantly, their IC50 against HL-60 cells were 0.38 ± 0.08 and 0.57 ± 0.05, respectively, demonstrating remarkable apoptosis and mod-erate cell cycle arrest at G1 phase. Intriguingly, an impressive safety profile for 5b was reflected by a 37.2 times selectivity against HL-60 over PBMC from a healthy donor. This provoked us to further explore their mechanism of action by in vitro and in silico tools. Conclusively, 5b and 5g stand out as strong chemotherapeutic agents that hold a clinical promise against acute myeloid leukemia.

Despite the recent advances in melanoma therapy, the need for new targets and novel approaches to therapy is urgent. We previously reported melanoma actives that work via binding and downregulating spliceosomal proteins hnRNPH1 and H2 (Palrasu et al., 2019). Given lack of knowledge about side effects of using spliceosomal binders in humans, an acute toxicity study was conducted to evaluate these compounds in mice. Male and female mice were treated with compounds 2155-14 and 2155-18 at 50mg/kg/day via subcutaneous injections and the clinical signs of distress were monitored for 21 days and compared with control mice. Additionally, effect of the leads on blood chemistry, blood cell counts, and organs was evaluated. No significant changes were observed in the mice body weight, blood cell count, blood chemistry, or organs following the compound treatment. The results show that our compounds 2155-14 and 2155-18 are not toxic for the study period of three weeks.

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: 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.

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.