Evaluating the potential mediating role of ADAMTS13 activity in the relationship between obesity and the severity of COVID-19: A retrospective cohort study.

Obesity and low enzyme A disintegrin and metalloproteinase with thrombospondin type-1 motif-13 (ADAMTS13) activity have been linked to poor coronavirus disease 2019 (COVID-19). Given that obesity may influence ADAMTS13 activity, it is feasible; however, it remains unclear whether ADAMTS13 activity acts as a mediator between obesity and COVID-19 outcomes. We investigated the link between body mass index (BMI) and COVID-19 outcomes, using ADAMTS13 activity as a mediator. ADAMTS13 activity was measured in 86 hospitalized COVID-19 patients. BMI, ADAMTS13 activity, and COVID-19 outcomes were assessed. Obese patients had a high odds ratio for low ADAMTS13 levels. When different levels of ADAMTS13 activity were considered, the severity of COVID-19 in obese patients was 4.5 times that in the normal BMI group. Furthermore, increased coagulopathy indicators correlated with low ADAMTS13 activity. Patients with elevated ALT and AST levels showed a 3 to 4-fold increase in the chances of low ADAMTS13 activity (OR:3.19, 95% CI:1.22-8.90, P = .021; OR:2.17, 95% CI:0.91-5.27, P = .082, respectively). When ADAMTS13 activity was considered, obese patients had greater COVID-19 severity and slower viral clearance than those with normal BMI. Low ADAMTS13 activity and impaired liver function are associated with poor COVID-19 outcomes. These findings encourage researchers to use molecular component identification to study the effects of obesity on the von Willebrand factor (VWF)/ADAMTS13 axis, COVID-19 pathogenesis, and outcomes.

Impact of aerobic and resistance training on fatigue, quality of life, and physical activity in prostate cancer patients: a systematic review and meta-analysis.

BACKGROUND: Prostate cancer (PCa) is a prevalent cancer with significant morbidity and mortality rates. In most cases, prostate cancer remains asymptomatic until advanced disease manifests with symptoms, such as benign prostate hyperplasia (BPH). Timely detection and better management have improved overall survival in patients with prostate cancer, and fatigue, reduced physical activity, and impaired quality of life (QoL) remain major challenges that impact daily life. OBJECTIVE: This study aimed to systematically review and conduct a meta-analysis to evaluate the impact of aerobic and resistance training on fatigue, quality of life, and physical activity in prostate cancer patients undergoing treatment. MATERIAL METHODS: A comprehensive literature search was conducted using the PubMed, Cochrane Library, and clinicaltrials.gov databases, adhering to the PRISMA guidelines. Twenty studies, involving 1393 participants, were included in the final analysis. The inclusion criteria were Studies that evaluated the effects of exercise interventions relative to passive controls in patients with prostate cancer were included. The primary outcomes of interest were fatigue, QoL, and PA.. Data from eligible studies were extracted, and a meta-analysis was performed using RevMan 5.40. RESULTS: Twenty studies met our inclusion criteria. Data Analysis of the included studies demonstrated a significant improvement in quality of life among prostate cancer patients in the exercise group compared to the control group (SMD=0.20, 95% CI=0.07 to 0.34, P=0.003). However, there was no significant association between exercise and fatigue (SMD=0.07, 95% CI=-0.13, 0.26, P=0.51). Sensitivity analysis did not alter these findings. Regarding physical activity outcomes, the control group exhibited superior performance in the 400-meter walk test (P<0.05). No significant associations were found between exercise and the 6-meter walk test or up-and-go time. CONCLUSION: This systematic review revealed that aerobic and resistance training enhance the quality of life of patients with prostate cancer, although it has a limited impact on fatigue and physical activity levels. These findings advocate a shift in clinical practice and positioning exercise as a core component of comprehensive cancer care. Tailoring exercise regimens according to individual patient needs and treatment stages should become the norm in treatment planning. This approach goes beyond physical wellness and addresses the psychological and emotional facets of cancer management. Moreover, there is an evident need for further research to develop holistic exercise interventions that effectively address the complex dynamics of fatigue, physical activity, and QoL in this patient group.

ADVANCING THE UNDERSTANDING OF CLINICAL SEPSIS USING GENE EXPRESSION-DRIVEN MACHINE LEARNING TO IMPROVE PATIENT OUTCOMES.

ABSTRACT: Sepsis remains a major challenge that necessitates improved approaches to enhance patient outcomes. This study explored the potential of machine learning (ML) techniques to bridge the gap between clinical data and gene expression information to better predict and understand sepsis. We discuss the application of ML algorithms, including neural networks, deep learning, and ensemble methods, to address key evidence gaps and overcome the challenges in sepsis research. The lack of a clear definition of sepsis is highlighted as a major hurdle, but ML models offer a workaround by focusing on endpoint prediction. We emphasize the significance of gene transcript information and its use in ML models to provide insights into sepsis pathophysiology and biomarker identification. Temporal analysis and integration of gene expression data further enhance the accuracy and predictive capabilities of ML models for sepsis. Although challenges such as interpretability and bias exist, ML research offers exciting prospects for addressing critical clinical problems, improving sepsis management, and advancing precision medicine approaches. Collaborative efforts between clinicians and data scientists are essential for the successful implementation and translation of ML models into clinical practice. Machine learning has the potential to revolutionize our understanding of sepsis and significantly improve patient outcomes. Further research and collaboration between clinicians and data scientists are needed to fully understand the potential of ML in sepsis management.

Comparison Between Fast-Track and Conventional Anesthesia for Children Undergoing Closure of Ventricular Septal Defects: A Systematic Review and Meta-Analysis.

Ventricular septal defect (VSD) is common in pediatric patients. This study aimed to evaluate the safety and effectiveness of using fast-track anesthesia and comparing it to traditional anesthesia, among children undergoing a transthoracic device closure for VSD. A systematic review following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. Relevant literature was identified through specific search terms in the Scopus, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (Embase), Web of Science, The Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. The inclusion criteria focused on observational studies that compared fast-track anesthesia with conventional anesthesia in pediatric VSD closure cases. Data extraction, quality assessment, and meta-analysis were performed using standard differences in means. Initially, 6,535 papers were identified, and subsequent screening of titles and abstracts led to the inclusion of four retrospective studies from a total of 51 studies. The analysis encompassed 477 patients, with 235 in the fast-track anesthesia group and 242 in the conventional anesthesia group. No statistically significant disparities were observed between the two groups concerning the operative duration and hemodynamic variations post-intubation or post-procedure (P >0.05). Nevertheless, the fast-track anesthesia group demonstrated significantly reduced healthcare expenses as well as shorter periods of mechanical ventilation, ICU stay, and overall hospitalization compared to conventional anesthesia (P <0.05). The use of fast-track anesthesia in combination with transthoracic device closure for VSD demonstrates a safe and effective approach for pediatric patients. This approach results in reduced healthcare costs (10,000 Renminbi (RMB)) and shorter durations of mechanical ventilation, ICU admission, and hospitalization compared to conventional anesthesia. Further clinical trials are necessary to confirm these results and assess long-term outcomes.

Atrial fibrillation in a child with multisystem inflammatory syndrome in children.

Atrial fibrillation (AF) is a rare complication of multisystem inflammatory syndrome in children (MIS-C) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A 10-year-old boy with a history of SARS-CoV-2 infection 10 weeks before presentation developed AF following the onset of MIS-C. The patient presented with high fever, conjunctival congestion, erythematous throat, and a diffuse erythematous macular rash involving the face and both legs, in addition to respiratory distress and shock requiring oxygen and vasopressor support. Echocardiography revealed poor left ventricular contractility and normal-appearing coronary vessels. The patient received intravenous immunoglobulin, pulse methylprednisolone, and aspirin. AF resolved with synchronized cardioversion and the patient's clinical condition subsequently improved. This case reports a rare phenomenon of AF in a case of MIS-C. Further research is required to verify the association.

A TRANSCRIPTOMIC APPRECIATION OF CHILDHOOD MENINGOCOCCAL AND POLYMICROBIAL SEPSIS FROM A PRO-INFLAMMATORY AND TRAJECTORIAL PERSPECTIVE, A ROLE FOR VASCULAR ENDOTHELIAL GROWTH FACTOR A AND B MODULATION?

ABSTRACT: This study investigated the temporal dynamics of childhood sepsis by analyzing gene expression changes associated with proinflammatory processes. Five datasets, including four meningococcal sepsis shock (MSS) datasets (two temporal and two longitudinal) and one polymicrobial sepsis dataset, were selected to track temporal changes in gene expression. Hierarchical clustering revealed three temporal phases: early, intermediate, and late, providing a framework for understanding sepsis progression. Principal component analysis supported the identification of gene expression trajectories. Differential gene analysis highlighted consistent upregulation of vascular endothelial growth factor A (VEGF-A) and nuclear factor κB1 (NFKB1), genes involved in inflammation, across the sepsis datasets. NFKB1 gene expression also showed temporal changes in the MSS datasets. In the postmortem dataset comparing MSS cases to controls, VEGF-A was upregulated and VEGF-B downregulated. Renal tissue exhibited higher VEGF-A expression compared with other tissues. Similar VEGF-A upregulation and VEGF-B downregulation patterns were observed in the cross-sectional MSS datasets and the polymicrobial sepsis dataset. Hexagonal plots confirmed VEGF-R (VEGF receptor)-VEGF-R2 signaling pathway enrichment in the MSS cross-sectional studies. The polymicrobial sepsis dataset also showed enrichment of the VEGF pathway in septic shock day 3 and sepsis day 3 samples compared with controls. These findings provide unique insights into the dynamic nature of sepsis from a transcriptomic perspective and suggest potential implications for biomarker development. Future research should focus on larger-scale temporal transcriptomic studies with appropriate control groups and validate the identified gene combination as a potential biomarker panel for sepsis.

Giant Coronary Aneurysm in an Infant with Multisystem Inflammatory Syndrome.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), also known as COVID-19, has rapidly spread resulting in a worldwide pandemic. Although COVID-19 infections in children are generally mild and nonfatal, there is increasing recognition of its association with the multisystem inflammatory syndrome in children (MIS-C), leading to serious illness and possible long-term complications. This report describes a 6-month-old Indian infant who presented with a 4-day history of fever with nonspecific signs of viral illness and erythematous rash. Although the initial echocardiogram was normal, subsequent scans showed progressive dilatation of bilateral coronary arteries. Despite the timely intervention, he developed left coronary artery thrombosis, leading to myocardial infarction. His SARS-CoV-2 antibody titers were strongly positive. Through this case, we discuss the management of MIS-C with coronary artery involvement. The long-term outcome of coronary artery aneurysm due to MIS-C remains unknown and close follow-up is important. Further research is pivotal for a better understanding of MIS-C.

Cardiovascular Toxicity Due to Otilonium Bromide Overdose: A Case Report.

BACKGROUND: Otilonium bromide is a quaternary ammonium compound commonly used in the management of irritable bowel syndrome. There are no previously published cases of overdose of otilonium bromide in humans. Due to its poor systemic absorption, it acts locally and has an excellent safety profile. Data from safety and postmarketing observation showed that otilonium bromide is well tolerated and that side effects do not differ significantly from those seen with placebo. The drug has proven to be practically toxicity free in animals and hence, assumed not to cause any specific problems in humans in case of overdose. CASE REPORT: We report a rare case of a 16-year-old girl who developed systemic hypotension (76/40 mm Hg) after an overdose of otilonium bromide tablets. She ingested 25 tablets of otilonium bromide (40 mg) over a period of 4 h. Subsequently, she responded to a bolus of normal saline and calcium gluconate, leading to normalization of her hemodynamic parameters. Why Should an Emergency Physician Be Aware of This? Due to a lack of reported cases, it is generally assumed that otilonium bromide overdose does not cause any specific problems in humans. However, with the drug being widely used for irritable bowel syndrome and other conditions, the chance of encountering cases of otilonium bromide overdose will increase. Through this case we aim to increase awareness among emergency physicians regarding the potential toxic effects of otilonium bromide overdosage.

Severe hypertension in pediatric diabetic ketoacidosis a case report and review of literature.

Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes mellitus in children. Despite the presence of dehydration, hypertension occurs in a significant proportion of children with DKA. There is a lack of clarity in the literature regarding the management of hypertension in patients with paediatric DKA. Herein, we report the case of an adolescent boy who presented with DKA and severe hypertension. His neurological status was closely monitored. There was a gradual decline in his blood pressure with an improvement in the pH over the next 72 hours. The combination of severe DKA and hypertension can be a challenging clinical dilemma, especially regarding fluid management. Studies on severe DKA in children are exacting, given the rarity of this condition. A multi-centre study is suggested to provide a meaningful analysis of this aspect of DKA.

A Novel Coupled Reaction-Diffusion System for Explainable Gene Expression Profiling.

Machine learning (ML)-based algorithms are playing an important role in cancer diagnosis and are increasingly being used to aid clinical decision-making. However, these commonly operate as 'black boxes' and it is unclear how decisions are derived. Recently, techniques have been applied to help us understand how specific ML models work and explain the rational for outputs. This study aims to determine why a given type of cancer has a certain phenotypic characteristic. Cancer results in cellular dysregulation and a thorough consideration of cancer regulators is required. This would increase our understanding of the nature of the disease and help discover more effective diagnostic, prognostic, and treatment methods for a variety of cancer types and stages. Our study proposes a novel explainable analysis of potential biomarkers denoting tumorigenesis in non-small cell lung cancer. A number of these biomarkers are known to appear following various treatment pathways. An enhanced analysis is enabled through a novel mathematical formulation for the regulators of mRNA, the regulators of ncRNA, and the coupled mRNA-ncRNA regulators. Temporal gene expression profiles are approximated in a two-dimensional spatial domain for the transition states before converging to the stationary state, using a system comprised of coupled-reaction partial differential equations. Simulation experiments demonstrate that the proposed mathematical gene-expression profile represents a best fit for the population abundance of these oncogenes. In future, our proposed solution can lead to the development of alternative interpretable approaches, through the application of ML models to discover unknown dynamics in gene regulatory systems.

Transcriptional instability during evolving sepsis may limit biomarker based risk stratification.

BACKGROUND: Sepsis causes extensive morbidity and mortality in children worldwide. Prompt recognition and timely treatment of sepsis is critical in reducing morbidity and mortality. Genomic approaches are used to discover novel pathways, therapeutic targets and biomarkers. These may facilitate diagnosis and risk stratification to tailor treatment strategies. OBJECTIVE: To investigate the temporal gene expression during the evolution of sepsis induced multi-organ failure in response to a single organism, Neisseria meningitidis, in previously healthy children. METHOD: RNA was extracted from serial blood samples (6 time points over 48 hours from presentation) from five critically ill children with meningococcal sepsis. Extracted RNA was hybridized to Affymetrix arrays. The RNA underwent strict quality control and standardized quantitation. Gene expression results were analyzed using GeneSpring software and Ingenuity Pathway Analysis. RESULT: A marked variability in differential gene expression was observed between time points and between patients revealing dynamic expression changes during the evolution of sepsis. While there was evidence of time-dependent changes in expected gene networks including those involving immune responses and inflammatory pathways, temporal variation was also evident in specific "biomarkers" that have been proposed for diagnostic and risk stratification functions. The extent and nature of this variability was not readily explained by clinical phenotype. CONCLUSION: This is the first study of its kind detailing extensive expression changes in children during the evolution of sepsis. This highlights a limitation of static or single time point biomarker estimation. Serial estimations or more comprehensive network approaches may be required to optimize risk stratification in complex, time-critical conditions such as evolving sepsis.

Characteristics of deaths in paediatric intensive care: a 10-year study.

OBJECTIVE: To describe the patient mortality over a 10-year period in a paediatric intensive care unit (PICU) including patient demographics, length of stay, cause and mode of death and to compare these findings with pre-existing literature from the western world. DESIGN: A retrospective chart review. SETTING: A UK tertiary PICU. PATIENTS: All children who died in the PICU over a 10-year period between 1 November 1997 and 31 October 2007 (n = 204). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data recorded for each patient included patient demographics, length of stay and cause of death according to the International Classification of Disease-10 classification, and mode of death. Mode of death was assigned for each patient by placement in one of four categories: (i) brain death (BD), (ii) managed withdrawal of life-sustaining medical therapy (MWLSMT), (iii) failed cardiopulmonary resuscitation (CPR) and (iv) limitation of treatment (LT). Over the study period, findings showed a median length of stay of 2 days (IQR 0-5 days), with a mortality rate of 5%. The most common mode of death was MWLSMT (n = 112, 54.9%) and this was consistent across the 10-year period. Linear regression analysis demonstrated no significant change in trend over the 10 years in each of the modes of death; BD (p = 0.84), MWLSMT (p = 0.88), CPR (p = 0.35) and LT (p = 0.67). CONCLUSION: End-of-life care is an important facet of paediatric intensive nursing/medicine. Ten years on from the Royal College of Paediatrics and Child Health publication 'Withholding or withdrawing life sustaining treatment in children: A framework for practice', this study found managed withdrawal of MWLSMT to be the most commonly practised mode of death in a tertiary PICU, and this was consistent over the study period.

New formulae for predicting tracheal tube length.

BACKGROUND: The aim of this study was to determine the accuracy of standard techniques for estimating oral and nasal tracheal tube length in children and to devise more accurate predictive formulae that can be used at the bedside. METHODS: Data were collected from 255 children who required tracheal intubation whilst on the Pediatric Intensive Care Unit over a period of 1 year. Age, weight, the final length of the tracheal tube and the internal diameter were documented. Patients with a tracheostomy were excluded from the study. RESULTS: Using linear regression the following formulae best predicted final tracheal tube length. For children over 1 year of age: Insertion depth (cm) for orotracheal intubation = age/2 + 13 Insertion depth (cm) for nasotracheal intubation = age/2 + 15 For children below 1 year of age: Insertion depth of orotracheal tube (cm) = weight/2 + 8 Insertion depth of nasotracheal tube (cm) = weight/2 + 9 CONCLUSIONS: Current Advanced Paediatric Life Support guidelines underestimate the appropriate tracheal tube lengths for orotracheal intubation in children over 1 year of age. Similarly, the novel weight-based formulae for tracheal tube lengths in children below the age of 1 year proved more accurate than standard reference charts. We therefore recommend that these new formulae are prospectively evaluated.

Sedation, analgesia, and neuromuscular blockade in the pediatric intensive care unit: survey of fellowship training programs.

OBJECTIVE: To survey current sedation, analgesia, and neuromuscular blockade practices in pediatric critical care fellowship training programs in the United States. DESIGN: Questionnaire survey sent by all program directors. The survey could be submitted either via a Web site, fax, or mail. SETTING: University school of medicine. SUBJECTS: Fifty-nine pediatric critical care fellowship training program directors in the United States, listed on the Accreditation Council for Graduate Medical Education Web site. INTERVENTIONS: Survey. MEASUREMENTS AND MAIN RESULTS: The response rate was 59.3% (35 questionnaires). Midazolam, lorazepam, morphine, and fentanyl are the most frequently used drugs in pediatric intensive care units for analgesia and sedation. Most pediatric intensive care units surveyed have a written sedation policy (66%). The majority of units responding to the survey (85.7%) routinely use a scoring system to assess agitation and pain in children, with the most common being the COMFORT score. All of the pediatric intensive care units surveyed reported weaning drugs slowly to try to prevent drug withdrawal. Movement disorders related to prolonged sedation and analgesia seem to be more common than is reported in the literature, with 65.7% of units reporting cases. There is good consensus on the indications for neuromuscular blockade, with vecuronium being the most popular drug. CONCLUSIONS: When compared with a similar survey from 1989, this survey suggests that pediatric critical care units with fellowship training programs have made some changes in their approach to sedation and analgesia over the past decade. More fellowship directors report the use of sedation protocols and better recognition, prevention, and management of drug withdrawal. Similar analgesic, sedative, and neuromuscular blocking drugs are being used but some more commonly than a decade ago.