Critical Care Outcomes Research Articles

Mortality and its predictors among patients with Guillain–Barré syndrome in the intensive care unit of a low-income country, Ethiopia: a multicenter retrospective cohort study

BackgroundGuillain–Barré syndrome (GBS) is a rare autoimmune disease that affects the peripheral nervous system. It is characterized by the destruction of nerves involved in movement. This condition can lead to transient pain, changes in temperature and touch sensations, muscle weakness, loss of sensation in the legs and/or arms, and difficulty swallowing or breathing. Published data on the outcomes of critical care for patients with GBS are extremely scarce in Africa, particularly Ethiopia. Therefore, this study aimed to assess mortality and its predictors among patients with GBS in the intensive care unit (ICU) of specialized hospitals in Ethiopia, a low-income country.Materials and methodsThis retrospective cohort study was conducted at the Tibebe Ghion Specialized Hospital and the Felege Hiwot Comprehensive Specialized Hospital in Bahir Dar, Ethiopia, from 1 January 2019 to 30 December 2023. Data were collected in the medical record rooms. Cox regression analysis was performed to identify the predictors of mortality among GBS patients in the ICU. The crude and adjusted hazard ratios (AHRs) and 95% confidence intervals (CIs) were calculated using bivariable and multivariable Cox regression models. A p-value of <0.05 was considered statistically significant.ResultsOf 124 GBS patients admitted to the ICU, 120 were included in the final analysis. During the follow-up, there were 23 (19.17%) deaths. The overall incidence rate of death was 1.96 (95% CI: 1.30, 2.95) per 100 person-days of observation. Traditional medicine (AHR = 3.11, 95%: 1.12, 16.70), COVID-19 infection (AHR = 5.44, 95% CI: 1.45, 73.33), pre-ICU cardiac arrest (AHR = 6.44, 95% CI: 2.04, 84.50), and ICU readmission (AHR = 4.24, 95% CI: 1.03, 69.84) were identified as the independent predictors of mortality.ConclusionThe mortality rate among GBS patients admitted to the ICU was high. Traditional medicine, COVID-19 infection, pre-ICU cardiac arrest, and readmission to the ICU were the significant predictors of mortality. Conducting large-scale studies with a prospective design in the future would yield more robust evidence.

Critical care admissions and outcomes in pregnant and postpartum women: a systematic review.

To synthesise evidence for the incidence of intensive care unit (ICU) admission, characteristics and mortality of pregnant and postpartum women with a focus on differences between high-income countries (HICs) and low-middle-income countries (LMICs) and report changes in reported findings since the last review by Pollock et al. (2010). We searched Ovid Medline, EMBASE, and CINAHL (2010-2023), following best practice guidelines for abstract screening for large-evidence systematic reviews. Patient and study characteristics of extracted studies were analysed descriptively. Multivariable meta-regression analysis, employing mixed-effects models, was conducted for assessing ICU admission and mortality. Studies reviewed by Pollock et al. were included to perform an overall analysis, including each study period and geographic region in a model. Seventy-one eligible studies reported data on 111,601 women admitted to ICU, with 41,291,168 deliveries reported in 65 studies. Fifty-six studies were retrospective. Case definitions, admission criteria, and causes of mortality reported were heterogeneous. The pooled ICU admission rate was 1.6% (95% confidence interval [CI] 1.28-1.99; I2 = 99.8%), 0.4% (95% CI 0.32-0.48, I2 = 99.9%) in HICs versus 2.8% (95% CI 0.65-6.4, I2 = 99.9%) in LMICs (p < 0.0001). The pooled ICU mortality rate among 140,780 admissions reported in 63 studies was 6.5% (95% CI 5.2-7.9; I2 = 98.7%), with mortality in HICs 1.4% (95% CI 0.8-2.1, I2 = 98.04%) lower than LMICs 12.4% (95% CI 8.1-17.5, I2 = 98.9%) (p < 0.0001). Multivariable meta-regression analysis found a significant association between the ICU admission rates (p = 0.0001) and mortality (p = 0.0003) with geographic region (HIC vs LMIC). Compared to the earlier study of Pollock et al. in 2010, there was an increase in reported studies (71 vs 40 in Pollock et al. study) and reported admissions (111,601 vs 7887 Pollock et al. study), particularly from LMICs'. Mortality for critically ill peripartum women is substantial and the gap in reported ICU admissions and mortality for critically ill peripartum women between HIC and LMICs remains unacceptably high. The reports are often small and heterogeneous using many case definitions. Reporting standards focusing on critical care processes and outcomes and large multinational prospective studies are necessary to better understand and mitigate maternal and child health challenges as sustainable development goals in LMICs and HICs.

Predictive value of the CURB-65, qSOFA, and APACHE II for in-hospital mortality in patients with acute exacerbation chronic obstructive pulmonary disease.

This study aimed to evaluate the efficacy of Quick Sequential Organ Failure Assessment, Confusion, Urea, Respiratory Rate, Blood Pressure, and Age Above or Below 65 Years (CURB-65), and Acute Physiology and Chronic Health Evaluation (APACHE) II in predicting the in-hospital mortality of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This retrospective study was conducted on 1583 hospitalized patients diagnosed with AECOPD from 2017 to 2019. Appropriate clinical data were retrieved from medical records from the time of admission up until the patients were discharged. The patients' most severe physiological condition and laboratory data within the first 24 hours of admission were used to determine CURB-65, Quick Sequential Organ Failure Assessment, and APACHE II scores. The accuracy of these 3 instruments in predicting the in-hospital mortality of patients with AECOPD was compared. It was observed that patients who had died had significantly higher APACHE II and CURB-65 scores (P < .05). Binary logistic regression analysis confirmed their significant association with mortality. The APACHE II score had a sensitivity of 91.6% and a specificity of 89.2%, while CURB-65 had a sensitivity of 94% and a specificity of 67.2%. The receiver operating characteristic curves for APACHE II and CURB-65 showed high predictive accuracy (area under the curve, 0.965 and 0.882, P < .001), respectively. Mortality rates substantially increased with higher scores (P < .001), reaching 38.2% for APACHE II scores ≥16 and 15.8% for CURB-65 scores ≥2. Our findings reveal a clear link between higher mortality rates and higher APACHE II and CURB-65 scores. The receiver operating characteristic curves' strong predictive ability highlights the dependability of these scoring systems in assessing the risk of in-hospital mortality, making them useful tools for predicting the outcomes in critical care.

Severe acute pancreatitis in the era of endoscopically placed lumen-apposing metal stents (LAMS): critical care outcomes from a large UK pancreatobiliary centre

Objectives1. Describe characteristics of patients with severe acute pancreatitis (SAP) requiring admission to Critical Care, including interventional management of pancreatic fluid collections.2. Quantify whether patients requiring drainage of collections via...

COMBINED CRITICAL ILLNESS–RELATED CORTICOSTEROID AND THYROID INSUFFICIENCY DURING TARGETED TEMPERATURE MANAGEMENT: A PROSPECTIVE COHORT STUDY

Objective. To study the effect of therapy for adrenal and thyroid dysfunction on the course and outcomes of critical care. Materials and methods. 51 patients requiring targeted temperature management (ТТМ) were included in a single-center prospective cohort study. Results. Group I (with adrenal and thyroid dysfunction) included 39 (76,5%) patients on TTM, group II (without adrenal and thyroid dysfunction ) included 12 (23,5%) patients without endocrinopathies. In patients on TTM, adrenal dysfunction developed on day (D) 0 and manifested only clinically in the form of vascular insufficiency. When evaluating clinical and laboratory data in patients at TTM, thyroid dysfunction was diagnosed at D1, D2, and D3. The manifestation of adrenal and thyroid dysfunction in patients at is primarily due to central nervous system injury rather than sepsis. Treatment of adrenal and thyroid dysfunction was performed with hydrocortisone and levothyroxine. Conclusion. Formation of combination of adrenal and thyroid dysfunction at TTM leads to the development of multiple organ dysfunction not associated with the development of septic complications. Timely diagnosis and adequate correction of adrenal and thyroid dysfunction in patients undergoing critical illness and requiring TTM allows to reliably reduce mortality.

Impact of Telemedicine on Patient-Centered Outcomes in Pediatric Critical Care: A Systematic Review

Background: Pediatric intensive care units (ICUs) face shortages of intensivists, posing challenges in delivering specialized care, especially in underserved regions. While studies on telecritical care in the adult ICU have demonstrated decreased complications and mortality, research on telemedicine in the pediatric ICU setting remains limited. This systematic review evaluates the safety and efficacy of audiovisual telemedicine in pediatric ICUs, assessing patient-centered outcomes when compared to in-person intensivist care. Methods: Two reviewers independently assessed studies from PubMed, MEDLINE (Ovid), Global Health, and EMBASE on the pediatric population in the ICU setting that were provided care by intensivists via telemedicine. Studies without a comparison group of in-person intensivists were excluded. Selected studies were graded using the Newcastle–Ottawa scale and the Levels of Evidence Rating Scale for Therapeutic Studies. Results: Of the 2419 articles identified, 7 met the inclusion criteria. Strong evidence suggested that telemedicine increases access to intensive care. Moderate evidence demonstrated that telemedicine facilitates real-time clinical decision-making, reliable remote clinical assessments, improved ICU process measures (i.e., days on a ventilator, days on antibiotics), and decreased length of stay. Weaker evidence supported that telemedicine decreases complications and mortality. Conclusions: Telemedicine may serve as a promising solution to pediatric ICUs with limited intensivist coverage, particularly in low-resource rural and international settings.

Survey of Continuous EEG Monitoring Practices in the United States.

Continuous EEG (cEEG) practice has markedly changed over the last decade given its utility in improving critical care outcomes. However, there are limited data describing the current cEEG infrastructure in US hospitals. A web-based cEEG practice survey was sent to neurophysiologists at 123 ACGME-accredited epilepsy or clinical neurophysiology programs. Neurophysiologists from 100 (81.3%) institutions completed the survey. Most institutions had 3 to 10 EEG faculty (80.0%), 1 to 5 fellows (74.8%), ≥6 technologists (84.9%), and provided coverage to neurology ICUs with >10 patients (71.0%) at a time. Round-the-clock EEG technologist coverage was available at most (90.0%) institutions with technologists mostly being in-house (68.0%). Most institutions without after-hours coverage (8 of 10) attributed this to insufficient technologists. The typical monitoring duration was 24 to 48 hours (23.0 and 40.0%), most commonly for subclinical seizures (68.4%) and spell characterization (11.2%). Larger neurology ICUs had more EEG technologists ( p = 0.02), fellows ( p = 0.001), and quantitative EEG use ( p = 0.001). This survey explores current cEEG practice patterns in the United States. Larger centers had more technologists and fellows. Overall technologist numbers are stable over time, but with a move toward more in-hospital compared with home-based coverage. Reduced availability of EEG technologists was a major factor limiting cEEG availability at some centers.

Predictive approach for liberation from acute dialysis in ICU patients using interpretable machine learning

Renal recovery following dialysis-requiring acute kidney injury (AKI-D) is a vital clinical outcome in critical care, yet it remains an understudied area. This retrospective cohort study, conducted in a medical center in Taiwan from 2015 to 2020, enrolled patients with AKI-D during intensive care unit stays. We aimed to develop and temporally test models for predicting dialysis liberation before hospital discharge using machine learning algorithms and explore early predictors. The dataset comprised 90 routinely collected variables within the first three days of dialysis initiation. Out of 1,381 patients who received acute dialysis, 27.3% experienced renal recovery. The cohort was divided into the training group (N = 1135) and temporal testing group (N = 251). The models demonstrated good performance, with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.81–0.88) and an area under the precision-recall curve of 0.69 (95% CI, 0.62–0.76) for the XGBoost model. Key predictors included urine volume, Charlson comorbidity index, vital sign derivatives (trend of respiratory rate and SpO2), and lactate levels. We successfully developed early prediction models for renal recovery by integrating early changes in vital signs and inputs/outputs, which have the potential to aid clinical decision-making in the ICU.

Critical care outcomes in decompensated cirrhosis: a United States national inpatient sample cross-sectional study

BackgroundPrior assessments of critical care outcomes in patients with cirrhosis have shown conflicting results. We aimed to provide nationwide generalizable results of critical care outcomes in patients with decompensated cirrhosis.MethodsThis is a retrospective study using the National Inpatient Sample from 2016 to 2019. Adults with cirrhosis who required respiratory intubation, central venous catheter placement or both (n = 12,945) with principal diagnoses including: esophageal variceal hemorrhage (EVH, 24%), hepatic encephalopathy (58%), hepatorenal syndrome (HRS, 14%) or spontaneous bacterial peritonitis (4%) were included. A comparison cohort of patients without cirrhosis requiring intubation or central line placement for any principal diagnosis was included.ResultsThose with cirrhosis were younger (mean 58 vs. 63 years, p < 0.001) and more likely to be male (62% vs. 54%, p < 0.001). In-hospital mortality was higher in the cirrhosis cohort (33.1% vs. 26.6%, p < 0.001) and ranged from 26.7% in EVH to 50.6% HRS. Mortality when renal replacement therapy was utilized (n = 1580, 12.2%) was 46.5% in the cirrhosis cohort, compared to 32.3% in other hospitalizations (p < 0.001), and was lowest in EVH (25.7%) and highest in HRS (51.5%). Mortality when cardiopulmonary resuscitation was used was increased in the cirrhosis cohort (88.0% vs. 72.1%, p < 0.001) and highest in HRS (95.7%).ConclusionsOne-third of patients with cirrhosis requiring critical care did not survive to discharge in this U.S. nationwide assessment. While outcomes were worse than in patients without cirrhosis, the results do suggest better outcomes compared to previous studies.

MORTALITY AND ASSOCIATED FACTORS AMONG INTENSIVE CARE UNIT ADMITTED ADULT PATIENTS WITH MECHANICAL VENTILATION IN ETHIOPIA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Introduction: The global demand for intensive care has risen, given its effectiveness in lowering mortality rates. Mechanical ventilation (MV) is integral to intensive care but introduces risks such as ventilator-associated complications. Ethiopia experiences a high intensive care unit (ICU) mortality rate. Objective: This systematic review and meta-analysis aim to comprehensively synthesize evidence on the mortality of adults undergoing MV in Ethiopia and identify associated factors. Methods: The study extensively searched databases and gray literature for research on MV outcomes, trends, and associated factors in adult ICUs. Adhering to the 2020 PRISMA checklist, a systematic review and meta-analysis sought to establish the mortality rate and key determinants among adult ICU patients on MV. The search incorporated keywords and MeSH terms, excluding studies with unsound methodologies or missing data. Data extraction, quality assessment, and analysis followed established protocols, including the JBI tool for methodological quality evaluation. STATA version 17.0 facilitated analysis, assessing heterogeneity, publication bias, and performing sensitivity and meta-regression analyses. Results: The pooled mortality rate among adult ICU patients undergoing MV was 48.61% (95% CI: 40.82, 56.40%). Significant mortality-contributing factors included medical diagnosis, Glasgow Coma Scale score, sepsis/septic shock, sedation use, multiple-organ dysfunction syndrome, and cardiovascular disease. Although some pooled odds ratios seemed insignificant, closer examination revealed significant associations in individual studies. Conclusion : The study underscores the urgent need for further research, improved ICU infrastructure, and healthcare personnel training in Ethiopia to enhance outcomes for mechanically ventilated patients. Identified factors offer valuable insights for targeted interventions, guiding tailored treatment strategies to reduce mortality. This study contributes to understanding mortality and associated factors in MV patients, informing initiatives to improve critical care outcomes in Ethiopia.

Telemedicine critical care availability and outcomes among mechanically ventilated patients

PurposeTelemedicine Critical Care (TCC) improves adherence to evidence based protocols associated with improved mortality among patients receiving invasive mechanical ventilation (IMV). We sought to evaluate the relationship between hospital availability of TCC and outcomes among patients receiving IMV. Materials and methodsWe performed a cross-sectional study of 66,522 adults who received IMV for non-postoperative acute respiratory failure at 318 non-federal hospitals in New York, Massachusetts, Maryland, and Florida in 2018. Hospital-level TCC availability was ascertained from the 2018 American Hospital Association Annual Survey. The primary outcome was in-hospital mortality. Secondary outcomes included the composite of tracheostomy or reintubation and duration of IMV. We used two-level hierarchical multivariable regression models to investigate the association between TCC availability and outcomes. Results20,270 (30.5%) patients were admitted into 89 TCC-available hospitals. There was no difference between TCC and non-TCC-available hospitals in mortality (odds ratio [OR] 0.94, 99% confidence interval [CI] 0.84–1.05), composite of tracheostomy or reintubation (OR 0.95 [0.82–1.11], or duration of IMV (OR 0.95 [0.83–1.09]). There was no difference in outcomes among the subgroup of patients with acute respiratory distress syndrome. ConclusionsHospital TCC availability was not associated with improved outcomes among patients receiving IMV.

Incidence of Weaning Failure in Obese Patients in Intensive Care Unit.

Background The escalating prevalence of obesity worldwide presents unique challenges in critical care management, especially in the context of mechanical ventilation and weaning processes in intensive care units (ICUs). The present study aimed to determine the incidence of weaning failure in obese patients in an ICU. Methods A prospective observational study was carried out to gather data on patients in the ICU of Shifa International Hospital located in Islamabad, Pakistan. The target population consisted of adult patients who were both male and female, ages 18 years and above. These individuals required intubation procedures as well as mechanical ventilation during their hospitalization. The researchers followed these patients prospectively and observed their medical conditions closely to gather data about how obesity might impact critical care interventions and outcomes. Results The sample size was 288 bearing a median age of 61.0 with an interquartile range of 19 years. Older age manifested a significantly higher frequency of failed extubation (p=0.065). Higher body mass index (BMI) was significantly associated with failed extubation among the study population. It was found that a higher significant difference was associated with BMI > 30 kg/m2 (obese) in failed and successful extubation. One-half of the patients with failed extubation and only 16 (5.9%) patients with successful extubation had end-stage renal disease (p<0.001). It was found that patients who underwent failed extubation had notably increased ICU mortality (p=0.108), 28-day mortality (p=0.067), as well as mean ICU (p<0.001) and hospital stay (p=0.007). Conclusion Our study revealed some insightful correlations between obesity, age, comorbidities, length of hospitalization, ICU stay, and mortality rate in terms of weaning failure among the study population.

Factors Affecting Mortality in Critically Ill Patients With Tuberculosis: A Systematic Review and Meta-Analysis.

Critically ill patients with tuberculosis carry high mortality. Identification of factors associated with mortality in critically ill tuberculosis patients may enable focused treatment. An extensive literature search of PubMed (MEDLINE), Embase, the Cochrane Library, and Google Scholar was performed using Medical Subject Headings terms "tuberculosis," "critical care," "critical care outcome," and "ICU." We aimed to identify factors affecting mortality in critically ill tuberculosis patients. All the studies comparing factors affecting mortality between survivors and nonsurvivors in critically ill tuberculosis patients were included. The database search yielded a total of 3017 records, of which 17 studies were included in the meta-analysis. Data were collected including the name of the author, year and country of publication, duration of the study, number of patients studied, type of tuberculosis, patient demography, smoking history, laboratory parameters, comorbidities, the requirement for mechanical ventilation, duration of ventilation, ICU and hospital length of stay (LOS), type of lung involvement, complications, and outcomes. The major factors that contributed to mortality in critically ill tuberculosis patients were age, platelet count, albumin, C-reactive protein (CRP), the requirement and duration of invasive mechanical ventilation, Pa o2 /F io2 ratio, presence of acute respiratory distress syndrome, shock, hospital-acquired infections, renal replacement therapy, and ICU and hospital LOS. Patient age, platelet count, albumin and CRP levels, the requirement and duration of invasive mechanical ventilation, Pa o2 /F io2 ratio, hospital-acquired infections, renal replacement therapy, and ICU LOS were variables associated with mortality.

Delirium and Its Associations with Critical Care Utilizations and Outcomes at the Time of Hospital Discharge in Patients with Acute Brain Injury.

Background and Objectives: We analyzed delirium testing, delirium prevalence, critical care associations outcomes at the time of hospital discharge in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), non-traumatic subarachnoid hemorrhage (SAH), non-traumatic intraparenchymal hemorrhage (IPH), and traumatic brain injury (TBI) admitted to an intensive care unit. Materials and Methods: We examined the frequency of assessment for delirium using the Confusion Assessment Method for the intensive care unit. We assessed delirium testing frequency, associated factors, positive test outcomes, and their correlations with clinical care, including nonpharmacological interventions and pain, agitation, and distress management. Results: Amongst 11,322 patients with ABI, delirium was tested in 8220 (726%). Compared to patients 18-44 years of age, patients 65-79 years (aOR 0.79 [0.69, 0.90]), and those 80 years and older (aOR 0.58 [0.50, 0.68]) were less likely to undergo delirium testing. Compared to English-speaking patients, non-English-speaking patients (aOR 0.73 [0.64, 0.84]) were less likely to undergo delirium testing. Amongst 8220, 2217 (27.2%) tested positive for delirium. For every day in the ICU, the odds of testing positive for delirium increased by 1.11 [0.10, 0.12]. Delirium was highest in those 80 years and older (aOR 3.18 [2.59, 3.90]). Delirium was associated with critical care resource utilization and with significant odds of mortality (aOR 7.26 [6.07, 8.70] at the time of hospital discharge. Conclusions: In conclusion, we find that seven out of ten patients in the neurocritical care unit are tested for delirium, and approximately two out of every five patients test positive for delirium. We demonstrate disparities in delirium testing by age and preferred language, identified high-risk subgroups, and the association between delirium, critical care resource use, complications, discharge GCS, and disposition. Prioritizing equitable testing and diagnosis, especially for elderly and non-English-speaking patients, is crucial for delivering quality care to this vulnerable group.

A Comprehensive Review of Inhaled Nitric Oxide Therapy: Current Trends, Challenges, and Future Directions.

This comprehensive review explores the multifaceted landscape of inhaled nitric oxide (iNO) therapy, tracing its historical evolution, mechanisms of action, clinical applications, challenges, and future directions. The nitric oxide signaling pathway, characterized by vasodilatory effects and anti-inflammatory properties, forms the foundation of iNO's therapeutic efficacy. Clinical applications are found in neonatal respiratory distress syndrome, pulmonary hypertension, and acute respiratory distress syndrome, showcasing its versatility. However, challenges, including cost considerations, technical intricacies, safety concerns, and resistance, highlight the nuanced landscape surrounding iNO therapy. Implications for clinical practice underscore the need for a tailored and evidence-based approach, considering individual patient characteristics and indications. Recommendations for future research emphasize ongoing exploration, novel indications, and the development of targeted therapies. In conclusion, this review positions iNO as a dynamic and adaptable intervention, poised to reshape therapeutic strategies and enhance patient outcomes in critical care.

Forecasting disease trajectories in critical illness: comparison of probabilistic dynamic systems to static models to predict patient status in the intensive care unit

ObjectiveConventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk...

Temporal trends in critical care utilization and outcomes in allogeneic hematopoietic stem cell transplant recipients.

Historically, the prognosis of allogeneic hematopoietic stem cell transplant (allo-HCT) recipients who require intensive care unit (ICU) admission has been poor. We aimed to describe the epidemiological trends of ICU utilization and outcomes in allo-HCT patients. We conducted a retrospective cohort study including adults (≥ 18) undergoing allo-HCT between 01/01/2005 and 31/12/2020 at Mayo Clinic, Rochester. Temporal trends in outcomes were assessed by robust linear regression modelling. Risk factors for hospital mortality were chosen a priori and assessed with multivariable logistic regression modelling. Of 1,249 subjects, there were 486 ICU admissions among 287 individuals. Although older patients underwent allo-HCT (1.64 [95% CI: 1.11 to 2.45] years per year; P = 0.025), there was no change in ICU utilization over time (P = 0.91). The ICU and hospital mortality rates were 19.2% (55/287) and 28.2% (81/287), respectively. There was a decline in ICU mortality (-0.38% [95% CI: -0.70 to -0.06%] per year; P = 0.035). The 1-year post-HCT mortality for those requiring ICU admission was 56.1% (161/287), with no significant difference over time, versus 15.8% (141/891, 71 missing) among those who did not. The frequency and duration of invasive mechanical ventilation (IMV) declined. In multivariable analyses, higher serum lactate, higher sequential organ failure assessment (SOFA) scores, acute respiratory distress (ARDS), and need for IMV were associated with greater odds of hospital mortality. Over time, rates of ICU utilization have remained stable, despite increasing patient age. Several trends suggest improvement in outcomes, notably lower ICU mortality and frequency of IMV. However, long-term survival remains unchanged. Further work is needed to improve long-term outcomes in this population.

The role of vitamin D in outcomes of critical care in COVID-19 patients: evidence from an umbrella meta-analysis of interventional and observational studies.

Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients. Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase. Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated. Adult patients suffering from COVID-19 were studied. Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, P < 0·001; I2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I2 = 00·0 %, P = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients. Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.

Demographic Profile and Outcome of Pediatric Intensive Care Unit.

Pediatric intensive care provides better observation as well as an intensive treatment, which helps to cure, support, and provide better outcomes for sick children. This study aimed to describe the demographic profile and the outcome of PICU patients, and evaluate the relationship of diagnostic categories with treatment and outcome. This retrospective cross-sectional study was conducted in a six-bedded PICU from 1 March 2021 to 1 March 2022. Bivariate analysis was used to identify the association between dependent and independent variables. The infants admitted below 6 months of age were 63 (22.3%) and had male predominance accounting for 64%. The main portal of entry of the admitted cases was emergency ward 214(75.6%). Most of the patients 153(54.1%) were admitted for intensive monitoring of their abnormal vitals along with critical care according to our PICU protocol. Respiratory illness 122(43.1%), neurosurgical illness 59(20.8%), and primary infectious disease 52(18.3%) were the common reason for PICU admission. Post-major surgery 2(66.7%), hematological illness 3(37.5%), and cardiac disorders 1(20%) had high mortality rates. Among the portal of admission, the majority of the children (80.0 %) who were admitted to the PICU through the emergency ward died before exiting from the PICU (p<0.0001). Respiratory illness was the most common cause of admission and post-major surgery had the highest mortality rate. Portal of entry was statistically associated with patient characteristics and had a significant relationship with the outcome. Similar studies in other health institutions are required to further analyze the demographic profile and outcome of pediatric critical care in Nepal.

Can Emergency Hematopoiesis Due to Sepsis Lead to Clonal Hematopoiesis? Implications for Understanding the Pathogenesis of Clonal Evolution

O.O &amp; T.K are co-first authors. Clonal (myelo) hematopoiesis of indeterminate potential (CHIP) arises from somatic mutations in myeloid genes, providing a proliferative and survival advantage to the affected “CHIP-initiating” early hematopoietic precursor cells. Understanding the conditions that lead to the emergence of detectable clones (early seeding of myeloid neoplasia-MN) is of great interest due to its clinical implications. Among CH facilitating states, aging has been extensively studied, but a clear distinction between the impact of chronological versus biological aging remains challenging. Additionally, other factors contributing to CHIP development may include chemotherapy, genetic predisposition, bone marrow failure states, or immunodeficiency. However, not all CHIP-promoting factors have been identified because they are subtle, pathophysiologically complex, and thus remain cryptic. We hypothesized that episodes of emergency hematopoiesis (EH), such as those caused by acute infections, could potentially result in acquisition of CHIP with repeated episodes of EH resulting in clonal expansion. If this hypothesis is confirmed, one could envision that both instances of significant hematopoietic expansion (high leukocytosis) and repeated cycles of EH could be at play in conjunction with chronological factors. For instance, the older an individual is, the greater is the number of EH episodes possible. To examine our theory, we prospectively collected blood samples from patients admitted at the intensive care unit (ICU) of Cleveland Clinic and Yale University. Inclusion criteria required a white blood cell (WBC) count ≥ 15K/uL. Patients with known or prior malignancies and those exposed to chemotherapy were excluded. For relevant comparisons, we assessed CH incidence in our cohort against a group of patients with solid tumors screened for CH (n=107) but without acute infections, along with historical CHIP cohorts. CH screening employed a targeted NGS myeloid gene panel with a reported VAF cut-off of 2%. A total of 78 individuals admitted to the ICU with possible infections and leukocytosis were enrolled in this study. The median age was 70 years (IQR: 61-77), with a M:F ratio of 1.7 (Table 1). Time from leukocytosis onset to sampling was 3 days (IQR: 1-5), the median WBC at ICU admission was 18 K/uL (IQR: 16-21), and the median absolute neutrophil count (ANC) was 16 K/uL (IQR: 12-20). Overall, 94 variants were identified including 16 (median VAF 50.1) variants of potentially germline origin, and 4 variants of unknown significance. We observed 74 CHIP-associated mutations in 37 (47%) patients at a median VAF of 14% (4-47%). The landscape of CHIP mutations included alterations in DNMT3A (20%), TET2 (12%), ASXL1 (12%), SMC1A, TP53, and PPM1D genes (6% each). Although higher rates of CHIP were expected in the cancer cohort, no difference was found between the two groups (40% vs. 47% in the ICU, p=0.3). DNMT3A, ASXL1 and PPM1D mutations were more frequently encountered in the cancer cohort (Table 1). The prevalence of CHIP in the ICU cohort was higher in older age groups: 30-39 (29%), 50-69 (49%), and ≥70 (51%), compared to the expected frequency in comparable age ranges (and median range) in a historical healthy population, which was 1%, 4%, and 10%, respectively (&amp;lt;0.00001; Fig.1). Notably, CHIP was more prevalent among smokers (57%; p=0.003). No significant differences were found when comparing CHIP + and CHIP - patients of the ICU cohort with regards to WBC (median 18K/uL both). Similarly, CHIP prevalence did not change according to the degree of leukocytosis in an analysis where patients were ranked by WBC (≥18K/uL at 44% vs. &amp;lt;18K/uL at 46%). When looking at the impact of CHIP on critical care outcomes, a logistic regression model accounting for age, gender, and mutation type revealed that the presence of DNMT3A mutations was associated with a higher risk of diagnosis of overt septic shock (log OR= 2.4, 95% CI 0.19-5.4, p&amp;lt;0.05). In summary, our prospective observational study has shown that sepsis is associated with preferential mutant clone expansion, primarily due to EH rather than the extent of leukocytosis and may be contributing to the acquisition of new clones. Whether such episodes result in permanent acquisition of new CHIP mutations with potential for MN progression will be the subject of longitudinal analysis of these samples, and findings will be presented at the ASH meeting.