Higher Mortality In Patients Research Articles

Immunization against Invasive Candidiasis is the Exigency of the Decade

Fungal infections by Candida spp. have emerged as one of the major concerns of high mortality in immunocompromised patients. It is one of the kingpins of the critical priority group of WHO fungal priority pathogens list 2022. Modern medicine has made its way for the better treatment of diseases and bacterial infections. But with drug-resistance in bacteria causing millions of deaths and to add on the trouble, invasive fungal infections which remains unnoticed is culminating into a challenge among the immunocompromised patients. A proper understanding of the host-pathogen interaction and the detailed immunology against fungal pathogens provides a better insight. This helps in development of efficient strategies for new generation antifungals and vaccination. In this review invasive fungal infections or fungemia caused by Candida species will be the heart. According to WHO fungal priority pathogens list (WHO FPPL 2022) for this group of fungus no commercial vaccine is available and it has become the need of this decade. The current efforts and preventive strategies studied against this infection will help in the up growth of vaccination against Invasive Candidiasis (IC).

Allogeneic stem cell transplant for multiple myeloma & myelofibrosis with split-dose busulfan, fludarabine & cyclophosphamide

Allogeneic stem cell transplant can have high morbidity and mortality in patients with myelofibrosis (MF) and multiple myeloma (MM). This phase 2 study used a novel myeloablative regimen of split-dose busulfan, fludarabine, and then post-transplant cyclophosphamide. Four patients with MF and 2 with MM were enrolled. At 1 year, non-relapse mortality was 33.3%, and overall survival was 50%. Incidence of acute and chronic GVHD was 33.3% and 16.7%, respectively. Those surviving beyond 1 year (MF = 1, MM = 2) had durable remissions with a median follow-up of 42 months. This small study demonstrates relative safety & favorable key outcomes using this novel approach.

National Early Warning Score 2 is superior to quick Sequential Organ Failure Assessment in predicting mortality in sepsis patients presenting to the emergency department in India: A prospective observational study.

High in-hospital mortality in sepsis patients remains challenging for clinicians worldwide. Early recognition, prognostication, and aggressive management are essential for treating septic patients. Many scores have been formulated to guide clinicians to predict the early deterioration of such patients. Our objective was to compare predictive values of quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2) with respect to in-hospital mortality. This prospective observational study was conducted in a tertiary care center in India. Adults with suspected infection with at least two Systemic Inflammatory Response Syndrome criteria presenting to the emergency department (ED) were enrolled. NEWS2 and qSOFA scores were calculated, and patients were followed until their primary outcome of mortality or hospital discharge. The diagnostic accuracy of qSOFA and NEWS2 for predicting mortality was analyzed. Three hundred and seventy-three patients were enrolled. Overall mortality was 35.12%. A majority of patients had LOS between 2 and 6 days (43.70%). NEWS2 had higher area under curve at 0.781 (95% confidence interval [CI] (0.59, 0.97)) than qSOFA at 0.729 (95% CI [0.51, 0.94]), with P < 0.001. Sensitivity, specificity, and diagnostic efficiency to predict mortality by NEWS2 were 83.21% (95% CI [83.17%, 83.24%]); 57.44% (95% CI [57.39%, 57.49%]); and 66.48% (95% CI [66.43%, 66.53%]), respectively. qSOFA score had sensitivity, specificity, and diagnostic efficiency to predict mortality of 77.10% (95% CI [77.06%, 77.14%]); 42.98% (95% CI [42.92%, 43.03%]); and 54.95% (95% CI [54.90%, 55.00%]), respectively. NEWS2 is superior to qSOFA in predicting in-hospital mortality for sepsis patients presenting to the ED in India.

CLINICAL CHARACTERISTICS, SEVERITY, AND OUTCOME OF ACUTE UPPER GASTROINTESTINAL BLEEDING IN ELDERLY AND NON-ELDERLY PATIENTS IN A TERTIARY CARE HOSPITAL- A PROSPECTIVE OBSERVATIONAL STUDY

Introduction: Upper gastrointestinal bleeding (UGIB) is a common emergency that requires hospitalization, and is more prevalent in men and older individuals. Age and co-morbidities are important factors for high mortality in UGIB patients, and elderly patients have an increased risk of mortality and morbidity compared to younger individuals. The type of UGIB experienced can also vary based on age. The Aim and objectives: aim of this study was to examine and compare the clinical characteristics, severity, and outcome of UGIB in elderly individuals (aged 60 or older) and non-elderly individuals (aged under 60) in Assam, India. Materials And Methods: This was a prospective observational study conducted at Assam Medical College and Hospital between April 2022 and September 2022. The study included adult patients presenting with UGIB. Patients below 18 years of age and in-patients who developed UGIB during hospitalization were excluded. A diagnosis of UGIB was based on the history of hematemesis and/or melena. Relevant blood and radiological investigations were conducted for all patients. All patients underwent upper GI endoscopy (UGIE). Data on clinical proles, laboratory reports, transfused blood/blood products, endoscopic ndings and interventions, and subsequent outcomes were collected prospectively for analysis. Results And Discussion: A total of 60 patients were included in the study, with a mean age of 42 years and 78.33% of patients being male. Of the 60 patients, 70% were non-elderly and 30% were elderly. The proportion of patients with co-morbidities and the use of non-steroidal anti-inammatory drugs or oral anti-coagulants was higher in the elderly group. The commonest mode of presentation among non-elderly patients was isolated melena (55%), while haematemesis in association with melaena was more common among elderly patients (50%). The proportion of patients with tachycardia and hypotension was signicantly higher among the elderly group. Variceal bleeding was signicantly higher among the elderly group (50% vs. 25%). The Rockall score, a measure of the severity of UGIB, was higher in 25% of elderly patients compared to 12

High in-hospital mortality and prevalence of cardiogenic shock in patients with ST-segment elevation myocardial infarction and concomitant COVID-19.

Published data suggest worse outcomes in acute coronary syndrome (ACS) patients with concomitant coronavirus disease (COVID-19) due to delays in standard management caused by burdened healthcare. To report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ST-elevation myocardial infarction (STEMI) patients and to compare these with the non-COVID-19 cohort hospitalized during the same period with the same access to medical care. From October 23rd, 2020 to April 23rd, 2021 (exactly 6 months) data were collected into a prospective ACS Registry. STEMI patients underwent invasive coronary angiography and were tested for COVID-19. Outcomes were in-hospital mortality and prevalence of cardiogenic shock. 125 patients, of whom 25 were COVID-19 positive, were admitted to the cardiology ward, and completed their hospital stay (i.e. discharge or death). There were no differences with regard to the time from symptom onset to reperfusion (median (Q1-Q3); 165 (130-202) vs. 170 (123-210), p = 0.86) and door-to-balloon time between the compared groups (25 (21-35) vs. 29 (21-59), p = 0.26). There was a higher GRACE risk score and mortality in the COVID-19 positive patients (180 (154-226) vs. 155 (132-181) and 48% vs. 10%, respectively, both p < 0.0001). Cardiogenic shock occurred more often in this group (32% vs. 13%; p = 0.035). COVID-19 positive patients had elevated high-sensitivity C-reactive protein (hsCRP) (p < 0.0001) and D-dimer (p = 0.003) and reduced left ventricular ejection fraction (p = 0.037). Postprocedural TIMI 3 flow grade was observed less frequently in this group (p = 0.044). High in-hospital mortality in patients with STEMI and COVID-19 did not result from delays in standard management, and could be related to increased thrombogenicity.

COVID-19 in people living with HIV: a single-center descriptive study

People living with human immunodeficiency virus (PLHIV) may suffer more severe symptoms of coronavirus disease 2019 (COVID-19) due to their immunocompromised status, even if they are undetectable. Human immunodeficiency virus (HIV) infection has been reported as an independent factor associated with higher mortality in patients with COVID-19. The present study aims to describe the clinical characteristics of PLHIV and COVID-19 in one center in Mexico. We conducted an observational retrospective monocentric cohort study of PLHIV diagnosed with COVID-19 between 1 March 2020 and 30 April 2021. SARS-CoV-2 was detected by polymerase chain reaction (PCR) of a nasopharyngeal swab sample, clinical features, and epidemiological characteristics. We identified 55 PLHIV with COVID-19. The median age was 36 years (IQR 25-41.5 years), and 54 patients were men. The median duration of HIV-1 infection was 4.3 years (Interquartile range, IQR 2.6-7.2 years), and 100% were on antiretroviral therapy (ART). The last HIV-1 RNA viral load analysis of the patients was 52/55 (94.5%) indicating that they were in virological suppression. The median CD4+ T-cell count was 734/mm3 (IQR 541.5-921/mm3). The most frequent pre-existing comorbidities found were obesity (21.8%), hypertension (7.2%), and diabetes (5.4%). Only one death was reported (1.8%). It has been reported that COVID-19/HIV/AIDS co-infection has a higher risk of mortality, admission to intensive care, and complications. However, our study found that people living with HIV-1 with adequate virological control did not present a severe course of COVID -19.

Association of Mortality with Lymphocyte Subset in Patients with COVID-19-associated Acute Respiratory Failure: A Subgroup Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pneumonia and lymphopenia. We investigated the predictive value of T-lymphocyte subset absolute counts for outcomes following coronavirus disease-2019 (COVID-19)-associated acute respiratory failure (C-ARF). A retrospective chart review of adult patients with C-ARF was undertaken from 23 March 2020 to 20 November 2021 to obtain relevant data. Patients were divided into two groups based on survival. The T-lymphocyte subsets were determined by flow cytometric analysis. A binomial logistic regression was performed to ascertain factors affecting survival. Cut-off values to differentiate between survivors and non-survivors were identified with the receiver operating characteristic (ROC) analysis. A total of 379 patients were analyzed. Age was negatively correlated with survival. Non-survivors had significantly lower T-lymphocyte subset absolute counts than survivors. Serum ferritin levels were significantly higher in non-survivors. Baseline lymphocyte (%) and a subset were predictive of survival in patients [lymphocyte (%) <5.65%, CD3+ <321 cells/µL, CD4+ <205 cells/µL, CD8+ <103 cells/µL]. Lower T-lymphocyte subsets were associated with higher mortality in patients with C-ARF. Monitoring trends may help in identifying patients at increased risk of poor outcomes. Vadi S, Pednekar A, Suthar D, Sanwalka N, Rabade N, Ghodke K. Association of Mortality with Lymphocyte Subset in Patients with COVID-19-associated Acute Respiratory Failure: A Subgroup Analysis. Indian J Crit Care Med 2023;27(1):52-56.

High incidence of intracranial haemorrhage in Egyptian children with congenital afibrinogenaemia.

Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality in patients with congenital afibrinogenaemia. Details on location of cerebral haemorrhage, management and neurological outcomes are lacking. We performed a retrospective study on Egyptian children with congenital afibrinogenaemia who experienced ICH, in order to estimate frequency, symptoms and neurological outcomes. Among 58 children with congenital afibrinogenaemia treated on demand, 18 (31%) had an history of ICH (28 episodes). The first ICH occurred at a median age of 1year (Q1-Q3 1-7 years). Impaired consciousness level, vomiting and seizures were the most common presenting symptoms. Spontaneous bleeding was associated with a more severe clinical presentation and worse neurological outcomes, including hydrocephaly and impaired cognitive development. Only half of ICH events (n=14) were treated in less than 24h from the onset of symptoms. Fibrinogen replacement by Fresh Frozen Plasma (FFP), cryoprecipitate or fibrinogen concentrates was administered in seven (25%), 19 (68%) and three (10%) ICH events, respectively. Overall, seven (25%) ICH occurring in four patients required a surgical intervention. After the ICH, six patients started secondary prophylaxis. The cumulative incidence of ICH at 10 years was 35% (95% CI 23-51) and at 20 years was 40% (95 CI% 26.7-58.8). In our cohort of children with congenital afibrinogenaemia, ICH was very frequent and associated with adverse neurological outcomes and death. Further studies are required to determine whether primary prophylaxis starting early in childhood is indicated after diagnosis.

The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia‐reperfusion injury via regulating NR2B‐ERK/CREB signaling

Cerebral ischemia-reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N-methyl-D-aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury. We used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen-glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR-ERK/CREB signaling. Treatment with Ast+Lig, or MK-801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca2+ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5-triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription-quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury. The overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B-ERK/CREB signaling pathway.

Double aortic dissection in a patient with Marfan disease. A case report

Marfan syndrome is a dominant autosomal genetic disease of the connective tissue, leading to various complications. Cardiovascular complications are the main ones, with dilation of the aorta and aortic dissection which is the main cause of death. Double dissection with different sites of departure is scarcely reported by the literature. We reported the case of a 22-year’s-old young patient admitted for acute chest and abdominal pains, and cardiogenic shock. Investigations reported a double dissection of the aorta with a recent one of type A and an old one of type B. Ghent diagnostic criteria were used to allow the diagnosis of Marfan disease. Surgical management corrected successfully the type A dissection. Early diagnostic and adequate management of aortic complications can reduce the high mortality rate of patients with Marfan syndrome.

Damage of cardiovascular system in patients with rare systemic diseases: example of recurrent polychondritis (case from practice)

A clinical case of recurrent polychondritis with damage to the cardiovascular system in the form of the development of acute coronary syndrome is presented. Recurrent polychondritis is a rare systemic presumably autoimmune disease that is affecting cartilage tissue. The main cause of high mortality in patients with systemic diseases is the early formation and accelerated progression of atherosclerotic vascular lesions that cause the development of myocardial infarction, stroke, chronic heart failure and sudden death. Recurrent polychondritis is characterized by clinical polymorphism. The diagnosis of the disease requires the interdisciplinary medical participation of at least five specialists.

Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with myeloid differentiation factor 2 (MD2).

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a challenging clinical syndrome that leads to various respiratory sequelae and even high mortality in patients with severe disease. The novel pharmacological strategies and therapeutic drugs are urgently needed. Natural products have played a fundamental role and provided an abundant pool in drug discovery. A compound library containing 160 natural products was used to screen potential anti-inflammatory compounds. Mice with LPS-induced ALI was then used to verify the preventive and therapeutic effects of the selected compounds. Licochalcone A was discovered from the anti-inflammatory screening of natural products in macrophages. A qPCR array validated the inflammation-regulatory effects of licochalcone A and indicated that the potential targets of licochalcone A may be the upstream proteins in LPS pro-inflammatory signalling. Further studies showed that licochalcone A directly binds to myeloid differentiation factor 2 (MD2), an assistant protein of toll-like receptor 4 (TLR4), to block both LPS-induced TRIF- and MYD88-dependent pathways. LEU61 and PHE151 in MD2 protein are the two key residues that contribute to the binding of MD2 to licochalcone A. In vivo, licochalcone A treatment alleviated ALI in LPS-challenged mice through significantly reducing immunocyte infiltration, suppressing activation of TLR4 pathway and inflammatory cytokine induction. In summary, our study identified MD2 as a direct target of licochalcone A for its anti-inflammatory activity and suggested that licochalcone A might serve as a novel MD2 inhibitor and a potential drug for developing ALI/ARDS therapy.

Pseudomonas aeruginosa PAO1 outer membrane vesicles-diphtheria toxoid conjugate as a vaccine candidate in a murine burn model

Pseudomonas aeruginosa is an opportunistic pathogen considered a common cause of nosocomial infection with high morbidity and mortality in burn patients. Immunoprophylaxis techniques may lower the mortality rate of patients with burn wounds infected by P. aeruginosa; consequently, this may be an efficient strategy to manage infections caused by this bacterium. Several pathogenic Gram-negative bacteria like P. aeruginosa release outer membrane vesicles (OMVs), and structurally OMV consists of several antigenic components capable of generating a wide range of immune responses. Here, we evaluated the immunogenicity and efficacy of P. aeruginosa PA-OMVs (PA-OMVs) conjugated with the diphtheria toxoid (DT) formulated with alum adjuvant (PA-OMVs-DT + adj) in a mice model of burn wound infection. ELISA results showed that in the group of mice immunized with PA-OMVs-DT + adj conjugated, there was a significant increase in specific antibodies titer compared to non-conjugated PA-OMVs or control groups. In addition, the vaccination of mice with PA-OMVs-DT + adj conjugated generated greater protective effectiveness, as seen by lower bacterial loads, and eightfold decreased inflammatory cell infiltration with less tissue damage in the mice burn model compared to the control group. The opsonophagocytic killing results confirmed that humoral immune response might be critical for PA-OMVs mediated protection. These findings suggest that PA-OMV-DT conjugated might be used as a new vaccine against P. aeruginosa in burn wound infection.

Growth Differentiation Factor 7 Prevents Sepsis-Induced Acute Lung Injury in Mice.

Acute lung injury (ALI) is a life-threatening complication during sepsis and contributes to multiple organ failure and high mortality for septic patients. The present study aims to investigate the role and molecular basis of growth differentiation factor 7 (GDF7) in sepsis-induced ALI. Mice were subcutaneously injected with recombinant mouse GDF7 Protein (rmGDF7) and then intratracheally injected with lipopolysaccharide (LPS) to generate sepsis-induced ALI. Primary peritoneal macrophages were isolated to further evaluate the role and underlying mechanism of GDF7 in vitro. GDF7 was downregulated in LPS-stimulated lung tissues, and rmGDF7 treatment significantly inhibited inflammation and oxidative stress in ALI mice, thereby preventing LPS-induced pulmonary injury and dysfunction. Mechanistically, we found that rmGDF7 activated AMP-activated protein kinase (AMPK), and AMPK inhibition significantly blocked the anti-inflammatory and antioxidant effects of rmGDF7 during LPS-induced ALI. Further findings revealed that rmGDF7 activated AMPK through a downregulated stimulator of interferon gene (STING) in vivo and in vitro. GDF7 prevents LPS-induced inflammatory response, oxidative stress, and ALI by regulating the STING/AMPK pathway. Our findings for the first time identify GDF7 as a potential agent for the treatment of sepsis-induced ALI.

Case Study: Abnormal Presentation of Infective Endocarditis With Streptococcus Canis and Chiari Network

Here we present a rare case of infective endocarditis (IE) with Streptococcus canis and Chiari network in an 85 year old female living with multiple dogs and open skin of lower extremity predisposing her to bacteremia. Underlying abnormalities of the cardiac chambers such as Chiari network predisposes to a higher incidence of bacterial seeding and causing IE. A Chiari network is usually asymptomatic and of no clinical significance but can worsen prognosis in IE. IE carries a significant morbidity and mortality burden and when diagnosed early can be a lifesaving diagnosis. Due to the wide range of complications, early diagnosis and treatment with targeted antimicrobial therapy and consideration of early surgical intervention are vital to the evaluation and treatment of IE. Though Staphylococci, Streptococci, Enterococci, HACEK organisms amount for the majority of IE, some atypical organisms including group G Streptococci such as S. canis have been reported to carry high mortality and hospitalization risk in patients with bacteremia. S. canis is a group G beta-hemolytic Streptococci which normally resides on the skin and mucosal surfaces of dogs. This Case Report shines light on the versatility of microorganisms that can cause IE in a patient with underling Chiari network, and the risk of morbidity and mortality with such species highlighting the importance of early diagnosis and treatment.

Impact of kidney transplant on post-operative morbidity and mortality in patients with pre-operative cardiac dysfunction.

Several studies show an increase in complications, both cardiac and non-cardiac, and a higher mortality in patients with preexisting cardiac disease when they undergo elective surgery. Due to the high incidence of cardiac dysfunction in patients with concomitant chronic kidney disease, we wanted to determine if the same negative impact is demonstrated in patients undergoing kidney transplantation. A retrospective analysis was done on 582 patients who underwent kidney transplant from a single transplant center between 2014 and 2019. Participants for this study were divided into two groups based on cardiac ejection fraction: normal EF (≥40%) (n=540) and low EF (<40%) (n=33); exclusion criteria included patients undergoing multi-organ transplants (n=9). Characteristics and outcomes of patients were compared before and after transplant using chi-square tests for categorical measures, and either Kruskal-Wallis or paired Student's t tests for continuous measures. Overall survival (OS) between groups was assessed using the Kaplan-Meier test. We compared outcomes between the normal EF and low EF groups using logistic regression in raw data, and propensity score matched sample and inverse-probability-weighting to mitigate selection bias. There was no significant difference in survival between patients in the low EF and normal EF groups (p=.33). Among patients with low EF, mean EF after transplant significantly improved (mean: 55.83% ± 5.75%) compared to mean EF before transplant (38.28% ± 7.35%), (p=<.0001). Of the patients with a low EF before transplant, 1 in 5 had a history of CAD, compared to only 1 in 10 among those patients with a normal EF, p=.0657. Post-transplant complications were comparable between the groups. Patients undergoing kidney transplantation with a low ejection fraction do not demonstrate an increased incidence of morbidity or mortality in the peri- and post-transplant follow-up compared with patients with a normal ejection fraction. Cardiac events post-transplantation is also comparable between the two groups. Of note, patients with a low EF have a significantly improved EF after kidney transplant which is likely a function of improvement in their physiologic state after the kidney transplant.

Rosmarinic acid protects against lipopolysaccharide-induced cardiac dysfunction via activating Sirt1/PGC-1α pathway to alleviate mitochondrial impairment.

Sepsis-induced cardiomyopathy is a decisive factor that plays a critical role in the high mortality of septic patients in the critically ill. Mitochondrial dysfunction occurring during sepsis is a vital contributor to the pathogenesis of myocardial damage. Rosmarinic acid (RA), a natural poly-phenolic compound, has showed cardio-protective and mitochondrial protective effect. The present study was aimed to investigate the effect of RA on sepsis-induced cardiomyopathy. Adult mice were subjected to intraperitoneal injection of saline (control) or lipopolysaccharide (LPS, 5mg/kg) to mimic sepsis-induced cardiomyopathy. Immediately after LPS challenge, vehicle or RA (100 mg/kg/day) was administrated via gavage. Cardiac function was examined with echocardiographic analyses 12 hours after LPS challenge and cumulative survival of mice was recorded for 8 days. Heart tissues were harvested 12 hours after LPS challenge to perform histological analyses and determine mitochondrial function. We found RA significantly improved cardiac function and survival of LPS-injected mice. Histologically, RA attenuated LPS-mediated cardiomyocyte damage, indicated by decreased cardiomyocyte apoptosis and improved myocardial swollen and disarrangement. Moreover, RA attenuated LPS-mediated myocardial mitochondrial dysfunction, indicated by improved mitochondrial ultrastructure, increased mitochondrial membrane potential (MMP), synthesis of adenosine triphosphate (ATP), markedly decreased reactive oxygen species (ROS) level and alleviated oxidative stress in heart tissues. RA treatment downregulated protein expression of Sirt1 and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and Sirt1 inhibition blocked protective effect of RA on LPS-induced myocardial damage and mitochondrial dysfunction. Collectively, RA attenuates LPS-induced cardiac dysfunction via activating Sirt1/PGC-1α pathway to alleviate mitochondrial impairment. It may be a promising cardio-protective drug to be used for septic patients.

Anti-Inflammatory Drug Therapy in Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis of Prospective Randomized, Double-Blind and Placebo-Controlled Trials.

Althoughanti-inflammatory drug therapy has been identified as potentially beneficial for patients suffering from chronic subdural hematoma (cSDH), contemporary literature presents contradictory results. In this meta-analysis, we aimed to investigate the impact of anti-inflammatory drug therapy on mortality and outcome. We searched for eligible randomized, placebo-controlled prospective trials (RTCs) on PubMed, Embase and Medline until July 2022. From 97 initially identified articles, five RTCs met the criteria and were included in our meta-analysis. Our results illustrate significantly lower rates of recurrent cSDH (OR: 0.35; 95% CI: 0.21-0.58, p = 0.0001) in patients undergoing anti-inflammatory therapy. In the subgroup of patients undergoing primary conservative treatment, anti-inflammatory therapy was associated with lower rates of "switch to surgery" cases (OR: 0.30; 95% CI: 0.14-0.63, p = 0.002). Despite these findings, anti-inflammatory drugs seemed to be associated with higher mortality rates in patients undergoing surgery (OR: 1.76; 95% CI: 1.03-3.01, p = 0.04), although in the case of primary conservative treatment, no effect on mortality has been observed (OR: 2.45; 95% CI: 0.35-17.15, p = 0.37). Further multicentric prospective randomized trials are needed to evaluate anti-inflammatory drugs as potentially suitable therapy for asymptomatic patients with cSDH to avoid the necessity of surgical hematoma evacuation on what are predominantly elderly, vulnerable, patients.

The Determining Factors for Outcome of Pediatric Intensive Care Admitted Children After Stem Cell Transplantation.

Requiring pediatric intensive care unit (PICU) admission relates to high mortality and morbidity in patients who received hematopoietic stem cell transplantation (HSCT). In this study, we aimed to evaluate the indications for PICU admission, treatments, and the determining risk factors for morbidity and mortality in patients who had allogeneic HSCT from various donors. In this retrospective study, we enrolled to patients who required the PICU after receiving allogeneic HSCT at our Pediatric Bone Marrow Transplantation Unit between 2005 and 2020. We evaluated to indication to PICU admission, applications, mortality rate, and the determining factors to outcomes. Thirty-three (7%) patients had 47 PICU admissions and 471 patients underwent bone marrow transplantation during 16-year study period. Also, 14 repeated episodes were registered in 9 different patients. The median age of PICU admitted patients was 4 (0.3 to 18) years and 29 (62%) were male. The main reasons for PICU admission were a respiratory failure, sepsis, and neurological event in 20, 8, and 7 patients, respectively. The average length of PICU stay was 14.5 (1 to 80) days, 14 (43%) of patients survived and the mortality rate was 57%. Multiple organ failure ( P =0.001), need for respiratory support ( P =0.007), inotrope agents ( P =0.001), and renal replacement therapy ( P =0.013) were found as significant risk factors for mortality. Allogeneic HSCT recipients need PICU admission because of its related different life-threatening complications. But there is a good chance of survival with quality PICU care and different advanced organ support methods.

238. Acalculous Cholecystitis: A Novel and Lethal Unrecognized Complication in Severe CoVID 19

Abstract Background SARS-COV-2 infection is known to cause tissue damage in several organs outside of the respiratory tract. The pathogenesis of tissue damage is hypothesized to be caused by direct viral damage, endothelial injury, and ischemic or thrombotic events. Gastrointestinal symptoms were first characterized mainly as diarrhea and diffuse abdominal pain and discomfort, which can be hard to interpret in the setting of a generalized inflammatory response; gallbladder injury and inflammation causing acute acalculous cholecystitis has been scarcely reported Methods Here we discuss five cases of patients presenting with symptoms of cholecystitis. All five patients underwent multiple imaging studies, and all of them were compatible with acute cholecystitis; some of them had an imaging report of lithiasic cholecystitis, while the rest were reported with microlithiasis or biliary sludge. Four out of the five patients underwent laparoscopic cholecystectomy; biopsies were taken, consistently those reported with acalculous cholecystitis. The remaining patient died of CoVID 19 complications prior to surgery, but after a percutaneous cholecystostomy tube was placed. Results All these patients have in common the prolonged fasting, because they all required invasive mechanical ventilation, consequently, they all developed multiple focal pneumonia and respiratory distress syndrome. This fast is related to the development of gangrenous ischemia in the gallbladder, which manifests as a late complication due to SARS-CoV-2 infection, in addition to being related to angiotensin-2 converting receptors and virus replication proteins, as well as the pro-inflammatory and hypoxia state that in itself causes the infection (9). All showed a cholestatic pattern, highlighting that this complication developed in an average time of 3 weeks after the onset of SARS-CoV2 symptoms, in addition to the fact that in most cases a negative test was already shown at the time of the complication. Conclusion Acalculous cholecystitis is one of the extrapulmonary complications that has been seen in patients with this infection, not being the most common, but one of those that has generated a higher mortality rate in patients due to its late diagnosis and non-specific clinical picture in certain occasions (9). Disclosures All Authors: No reported disclosures.