Sepsis Syndrome Research Articles

The safety and efficacy of imatinib a tyrosine kinase inhibitor for the treatment of SARS-COV-2 induced pneumonia: a pilot study

Introduction Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a wide spectrum of disease, approximately 15–20% of affected patients present with severe phenotype that require supplemental oxygen, including up to 5% who may develop critical illness. The main therapeutic strategies proposed for the management of COVID-19 pneumonia are direct antiviral and immunomodulatory treatments aiming to prevent disease progression. In this pilot study we are testing the hypothesis of using imatinib a tyrosine kinase inhibitor (TKI) as an immunomodulatory treatment to prevent disease progression, based on encouraging data from cellular, animal models and clinical trials, showing a beneficial role of TKI in the regulation of inflammation and endothelial barrier integrity, as well as their antiviral properties. Aim The primary end point is to assess the effect of the imatinib treatment, in terms of safety and efficacy, to prevent the progression of patients with moderate to severe COVID-19 pneumonia into critical illness and need for invasive mechanical ventilation. The secondary end point is a composite of change in clinical, laboratory and radiological parameters, including: clinical parameters − the percentage of patients reaching normal hypoxic index (HI) at time of hospital discharge, hospital length of stay and days on mechanical ventilation (MV) in patient intubated and mechanically ventilated, the changes in the levels of laboratory inflammatory markers: serum ferritin, serum C reactive protein (CRP), serum interleukin 6 (IL6), viral clearance presented by the delta time till negative SARS-CoV-2 PCR results, as well as the change in the chest radiological parameters (Computed tomography chest or radiography). Methods Thirty SARS-COV-2 positive patients with moderate to severe respiratory symptoms, were enrolled and randomized into three groups: group 1 Control, group 2 Low dose Imatinib (receiving 200 mg Imatinib/day) and group 3 Standard dose Imatinib (receiving 400 mg Imatinib/day). Results There was no significant difference between the three groups regarding the severity of the disease at baseline, as assessed by clinical, laboratory and radiological parameters. There was a nonstatistically significant difference in the primary end point of the study, regarding the number of patients in need for invasive mechanical ventilation, between the control group and the intervention groups receiving imatinib. Conclusion Despite the negative results regarding the efficacy of imatinib to flatten the curve of the illness and the prevention of more severe phenotype of the disease, our study showed positive findings regarding the medication’s safety and patients’ tolerability. These finding would pave the way for further studies to assess the concept of immunomodulation in the treatment of immunity derived disease, like sepsis and acute respiratory distress syndrome (ARDS).

Comparison of the VITEK® 2 System with Conventional Methods for Species Identification and Antimicrobial Susceptibility Pattern of Staphylococcal Carrier Isolates

Staphylococcus aureus, an opportunistic pathogen that inhabits 20% to 70% of human anterior nares and can cause infections, ranging from mild, superficial infections of the skin and soft tissues to severe conditions like sepsis, necrotizing pneumonia and toxic shock syndrome. Healthcare workers are potential asymptomatic nasal carriers, contribute to major infection transmission. The emergence of multidrug-resistant strains necessitates advanced treatment approaches. The study aimed to identify staphylococcal nasal carriers among dental students, and to compare the results obtained from automated identification system, VITEK® 2 with conventional methods for identifying Staphylococcus species and determining antibiotic susceptibility patterns. Anterior nasal swabs were collected from 42 study participants were processed as per standard microbiological culture techniques. All the conventionally identified S. aureus isolates were subjected to a further analysis using an automated VITEK® 2 SYSTEM. Surprisingly, the automated identification system classified all conventionally proven S. aureus isolates as other Staphylococci species (S. epidermidis (60%), S. warneri, and S. lentus), raising concerns about potential misdiagnosis. Overall, there was a 97.5% categorical agreement between VITEK® 2 system and the reference method, with minimal errors (0.8% very major, 0.6% major, and 1.17% minor). These discrepancies underscore the importance of accurate species identification and highlight the necessity for advanced techniques in infection control strategies, emphasizing the potential impact on decolonization decisions.

Acute Kidney Injury Among COVID-19-Positive Patients Is Associated With Higher Mortality: A Single-Center Experience.

Renal complications of COVID-19 are not yet well studied. We aimed to evaluate acute kidney injury prevalence among hospitalized patients with COVID-19 infection and explore its effect on patient outcomes. We retrospectively evaluated 586 hospitalized patients with COVID-19. Of these patients, 267 (45.5%) developed acute kidney injury, as classified according to the Kidney Disease Improving Global Outcomes guidelines. We compared this group with 319 patients (54.5%) without acute kidney injury. Most patients in both study groups were men; mean age was 60.8 ± 14 versus 51.7 ± 16 years. Comorbid conditions that were substantially predominant among patients with acute kidney injury were diabetes mellitus (64% vs 42.9%), hypertension (72.6% vs 43.5%), and ischemic heart disease (25% vs 14.7%). Fever, cough, shortness of breath, and dehydration were the main presentations among patients with acute kidney injury, and patients in this group had greater prevalence of radiological findings concordant with COVID-19 (86.8% vs 59.8%). Sepsis, volume depletion, shock, arrhythmias, and acute respiratory distress syndrome were higher in patients with acute kidney injury. Anticoagulation (85% vs 59.2%), vasopressors, plasma infusions, antimicrobials, and steroids were more frequently used in patients with acute kidney injury. More patients with acute kidney injury had acute respiratory failure requiring mechanical ventilation (62.3% vs 32.9%), with higher overall mortality rate (63.2% vs 31.1%). We found more frequent prevalence of acute kidney injury associated with severe COVID-19 than shown in reports from Chinese, European, and North American cohorts. Patients with COVID-19 who developed acute kidney injury had risk factors such as hypertension and diabetes, greater need for mechanical ventilation, were males, and were older age. Mortality was high in this population, especially among older patients and those who developed Kidney Disease Improving Global Outcomes stage 3 disease.

Strongyloides stercoralis-induced sepsis and acute respiratory distress syndrome in a patient with Guillain-Barré syndrome.

Strongyloides stercoralis-induced sepsis and acute respiratory distress syndrome in a patient with Guillain-Barré syndrome.

Descriptive Analysis of Neonatal Mortality during May 2023 at Holy Family Hospital Rawalpindi

Although child mortality has substantially been declined due to stringent efforts for achieving the set targets meant to attain health related Millenium Development Goals (MDGs) by 2015, yet the reduction in neonatal mortality has been noted at comparatively slower pace. Considerable neonatal deaths have also been reported in South Asan regions of the globe. Objective: To analyze neonatal mortality in terms of place of delivery, antenatal booking and maternal as well as medical causes of death. Methods: A cross-sectional descriptive study was done during May 2023 to determine various attributes of neonatal mortality like delivery site and antenatal visits. In addition to maternal factors contributing to neonatal mortality, post-delivery mortality reasons were also recorded. Data were entered and analyzed by using Microsoft Excel 2016. Results: Out of 100 neonatal mortalities about 88.5% were early neonatal deaths. 21% and 79% were home and hospital delivered neonates respectively. Of the 49 booked cases, 35% were delivered in private hospitals while 25.5% of the remaining non-booked cases were delivered in private healthcare facilities. Approximately 47% and 53% were preterm and full-term births respectively. 35.6% neonates died of bacterial sepsis while 22% and 19% neonates succumbed to respiratory distress syndrome and intrauterine hypoxia respectively. Conclusions: There were considerable early neonatal deaths and majority died of bacterial sepsis and respiratory distress syndrome.

Definition, epidemiology and characterization of sepsis

Sepsis is a condition that occurs when the body's response to infection becomes unbalanced and potentially life-threatening. In this study, there is a focus on understanding and addressing sepsis. This detailed review explores how sepsis is defined in its prevalence in populations and how it is present clinically. The development of sepsis involves a series of events triggered by infections resulting in inflammation and dysfunction in organs. The symptoms of sepsis can range from signs like fever and changes in state to more severe complications such as septic shock. Early recognition of these symptoms using criteria like Systemic inflammatory response syndrome (SIRS) is crucial for intervention, which can greatly impact patient outcomes. Various diagnostic markers, imaging techniques and a deeper understanding of the pathophysiology behind sepsis have contributed to identification and targeted treatment approaches. Managing sepsis involves a combination of therapy, support for blood circulation, respiratory interventions and careful use of agents that modulate the system. It's important to emphasize the efforts among healthcare professionals from disciplines when it comes to managing sepsis effectively. Providing follow up care is essential for survivors as they may experience long term consequences such as sepsis syndrome. Due to its impact on health ongoing research is necessary to explore therapeutic options and refine existing strategies for managing sepsis effectively. The field continues to evolve with advancements, in precision medicine host directed therapies and interdisciplinary collaboration playing roles. This review seeks to grasp the concept of sepsis, providing insights into its various aspects, including the difficulties, in diagnosis and the ever-evolving treatment strategies.

CONTEMPORARY PERSPECTIVES ON DIAGNOSING ACUTE PANCREATITIS

Acute pancreatitis represents a significant challenge in urgent surgery. It holds a prominent position among urgent surgical diseases, with a rising incidence of severe, complicated forms. The increase in the negative outcomes of acute pancreatitis treatment is linked to delayed diagnosis of severe forms and their complications, owing to the absence of a highly effective severity assessment scale. This deficiency contributes to unjustified surgical interventions. Early severe pancreatitis manifests with a rapidly progressive course leading to organ failure, hypoxia, necrotic foci formation, abdominal sepsis, and abdominal compartment syndrome. Specific scales for early diagnosis include the criteria scale for primary assessment of acute pancreatitis severity, the Ranson scale, and the BISAP scale. The modern diagnosis of severe acute pancreatitis relies on two key international classifications: the Revised Atlanta Classification (2012) and the Determinant-based classification (2012). To assess the intensity of pancreatic inflammation by CT scan, the Balthazar scale is used, which is included in the Computer Tomography Severity Index and enables to determine the area of pancreatic necrosis.
 The purpose of this study is to improve the diagnosis of acute severe pancreatitis.
 The study was carried out by assessing the medical records of 20 patients diagnosed with acute pancreatitis who received treatment at the Surgical Inpatient Department of the 2nd City Hospital, Poltava, from 2021 to 2022.
 The analysis revealed that conducting a computer tomography within the 48-72 hours from the onset of the disease enables a comprehensive assessment of its severity. This assessment significantly influences the subsequent treatment approach, reducing the necessity for surgical intervention and lowering the risk of patient mortality.
 Hence, in alignment with contemporary classifications and diagnostic perspectives on acute pancreatitis, MSCT assumes a pivotal role, significantly influencing the selection of treatment strategies in all cases. This inclusion facilitates timely surgical interventions and allows for adjustments to conservative therapy based on the severity of pancreatic inflammation. It is advisable, however, to conduct computed tomography 48-72 hours after the onset of pain to adequately assess the pancreatic condition. Morphological changes in the pancreas typically do not manifest within the initial day of the disease, making early CT diagnostics potentially misleading regarding the true state and severity of acute pancreatitis.

Acacetin protects against sepsis-induced acute lung injury by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis.

Acute lung injury (ALI) is the leading cause of death in patients with sepsis syndrome and without effective protective or therapeutic treatments. Acacetin, a natural dietary flavonoid, reportedly exerts several biological effects, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, acacetin's effect and underlying mechanism on sepsis-induced ALI remain unclear. Here, the mouse model was established to explore the impact of acacetin on sepsis-induced ALI. Acacetin significantly increased ALI murine survival and attenuated lung injury in histological examinations. Additionally, acacetin down-regulated myeloperoxidase activity, protein concentration, and number of neutrophils and macrophages in bronchoalveolar lavage fluid. Subsequently, inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were examined. Results showed that acacetin dramatically suppressed the production of TNF-α, IL-1β, and IL-6. These above results indicated that acacetin attenuated sepsis-induced ALI by inhibiting the inflammatory response. Moreover, acacetin inhibited the expression of markers for M1-type (iNOS, CD86) macrophages and promoted the expression of markers for M2-type (CD206, Arg1) macrophages by western blot. In addition, acacetin down-regulated the expression TRAF6, NF-κB, and Cyclooxygenase-2 (COX2) by western blot. The high concentration of acacetin had a better effect than the low concentration. Besides, over-expression of TRAF6 up-regulated the expression of COX2, CD86, and iNOS, and the ratio of p-NF-κB to NF-κB increased the mRNA levels of TNF-α, IL-1β, and IL-6, down-regulated the expression of CD206 and Arg1. The effects of TRAF6 were the opposite of acacetin. And TRAF6 could offset the impact of acacetin. This study demonstrated that acacetin could prevent sepsis-induced ALI by facilitating M2 macrophage polarization via TRAF6/NF-κB/COX2 axis.

The efficacy of Omega-3 polyunsaturated fatty acids for severe burn patients: A systematic review and trial sequential meta-analysis of randomized controlled trials

Severe burns lead to metabolic changes, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Omege-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties. In the absence of substantial evidence for use on major burns, we systematically reviewed the efficacy of omega-3 PUFAs for patients with severe burns. We comprehensively searched MEDLINE, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, Wang Fang Data, Chinese Biomedicine Database, and Science Direct databases to collect randomised controlled trials of omega-3 PUFAs administered to patients with burns from January 2000 to June 2023. Two researchers independently screened the literatures, extracted the data, and assessed the risk of bias in the included studies. The outcomes were mortality, the risk of severe sepsis, septic shock, and multiple organ dysfunction syndrome. Data synthesis was conducted using Review Manager. Trial sequential analyses (TSA) for outcomes were performed. Three randomised controlled trials involving 140 patients were included. Of these, 71 patients received omega-3 PUFAs. The results showed that omega-3 PUFAs significantly reduced the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome (RR=0.38, 95% CI [0.19, 0.75], P=0.005), C-reactive protein levels (MD=-39.70[-81.63, 2.23], P=0.06), and improved respiratory outcomes. However, there was no difference in 14-day mortality (RR=1.10, 95%CI [0.59, 2.05], P=0.75). TSA showed that the results for the incidence of severe sepsis, septic shock, multiple organ dysfunction syndrome are insufficient and inconclusive. Omega-3 PUFAs may reduce inflammatory response and risk of sepsis, septic shock, and multiple organ dysfunction syndrome in severe burns patients and may shorten hospital stay but cannot reduce risk of death. Due to the limitation of the quantity and quality of the included studies, the evidence level is low, and the conclusions need to be verified by larger scale and higher quality randomised controlled trials.

The erythromycin polyketide compound TMC-154 stimulates ROS generation to exert antibacterial effects against Streptococcus pyogenes

The erythromycin polyketide compound TMC-154 is a secondary metabolite that is isolated from the rhizospheric fungus Clonostachys rogersoniana associated with Panax notoginseng, which possesses antibacterial activity. However, its antibacterial mechanism has not been investigated thus far. In this study, proteomics coupled with bioinformatics approaches was used to explore the antibacterial mechanism of TMC-154. KEGG pathway enrichment analysis indicated that eight signaling pathways were associated with TMC-154, including oxidative phosphorylation, cationic antimicrobial peptide (CAMP) resistance, benzoate degradation, heme acquisition systems, glycine/serine and threonine metabolism, beta-lactam resistance, ascorbate and aldarate metabolism, and phosphotransferase system (PTS). Cell biology experiments confirmed that TMC-154 could induce reactive oxygen species (ROS) generation in Streptococcus pyogenes; moreover, TMC-154-induced antibacterial effects could be blocked by the inhibition of ROS generation with the antioxidant N-acetyl L-cysteine. In addition, TMC-154 combined with ciprofloxacin or chloramphenicol had synergistic antibacterial effects. These findings indicate the potential of TMC-154 as a promising drug to treat S. pyogenes infections. SignificanceStreptococcus pyogenes is a nearly ubiquitous human pathogen that causes a variety of diseases ranging from mild pharyngitis and skin infection to fatal sepsis and toxic heat shock syndrome. With the increasing incidence of known antibiotic resistance, there is an urgent need to find novel drugs with good antibacterial activity against S. pyogenes. In this study, we found that TMC-154, a secondary metabolite from the fungus Clonostachys rogersoniana, inhibited the growth of various bacteria, including Staphylococcus aureus, S. pyogenes, Streptococcus mutans, Pseudomonas aeruginosa and Vibrio parahemolyticus. Proteomic analysis combined with cell biology experiments revealed that TMC-154 stimulated ROS generation to exert antibacterial effects against S. pyogenes. This study provides potential options for the treatment of S. pyogenes infections in the future.

Purification, characterization, and cloning of a novel pro-inflammatory secreted protein from Staphylococcus aureus.

Staphylococcus aureus causes a myriad of human diseases, ranging from relatively mild soft tissue infections to highly fatal pneumonia, sepsis, and toxic shock syndrome. The organisms primarily cause diseases across mucosal and skin barriers. In order to facilitate penetration of barriers, S. aureus causes harmful inflammation by inducing chemokines from epithelial cells. We report the cloning and characterization of a novel secreted S. aureus protein that induces chemokine production from epithelial cells as its major demonstrable function. This secreted protein possibly helps S. aureus and its secreted proteins to penetrate host barriers.

Incidence, Risk Factors, and Outcomes of Acute Kidney Injury in Preterm Neonates Hospitalized in the Neonatology Unit, North India: A Single-center Experience.

Acute kidney injury (AKI) is common in premature newborns and is associated with high mortality. It is unclear which risk factors lead to AKI in these neonates. We aimed to determine the incidence, risk factors, and outcomes of AKI in preterm neonates in the neonatal intensive care unit (NICU). They were screened and staged for AKI as per the amended neonatal criteria of Kidney Disease Improving Global Outcomes and followed up until discharge or death. Serum creatinine levels and urine output were measured. The incidence of AKI was 18.5% (37/200 neonates). The majority developed non-oliguric AKI. The risk factors significantly associated with AKI in neonates were the presence of sepsis, birth asphyxia, shock, respiratory distress syndrome, and hypothermia. The majority of neonates with AKI had a birthweight <1500 g and a gestational age of <32 weeks and had a higher risk of mortality, in contrast to than those without AKI. Mortality and NICU stay were significantly higher among those with Stage 3 AKI compared with Stage 2 and Stage 1 AKI. To prevent AKI and reduce the burden of high mortality in premature neonates, it is essential to prevent sepsis, birth asphyxia, and respiratory distress syndrome, as well as to detect shock and patent ductus arteriosus as early as possible. There is a need for good antenatal care to reduce the burden of prematurity.

Liver Abscesses Due to Fusobacterium nucleatum: A Case Series

Abstract Fusobacteriae are anaerobic gram-negative bacilli, classically involved in the development of septic thrombophlebitis of the internal jugular vein in Lemierre syndrome. The goal of this study is to describe the various presentations, treatment course, and outcomes of patients with Fusobacterium liver abscess(es) and review available literature on this topic. We retrospectively reviewed our microbiologic database for positive cultures of Fusobacteriae species in a tertiary care hospital from July 2018 through November 2022 and identified 5 cases of liver abscess that involved Fusobacterium nucleatum species. Patients presented with a syndrome of fever and chills, abdominal pain, and nausea and vomiting. Laboratory investigations revealed leukocytosis and transaminitis, and imaging revealed liver abscess(es). The identification of the F. nucleatum bacteria involved invasive aspiration of the abscess in all but one case, where it was identified on blood cultures. One patient had a florid picture of sepsis and acute respiratory distress syndrome. All patients responded well with intravenous antibiotics and were discharged home to complete a prolonged course until radiographic resolution. In 3 patients, history and imaging were suggestive of possible sources that may have hematogenously spread to the liver, with history of recent appendectomy in 1 patient, possible appendicitis on computed tomography of the abdomen in another patient, and recent dental manipulation in the third patient. In conclusion, Fusobacteriae should be included in the differential diagnosis of liver abscess, especially in the setting of recent appendicitis or dental disease. Effective treatment includes surgical drainage when feasible and prolonged course of antibiotics with goal of radiologic resolution.

Delta Neutrophil Index as a New Marker of Purulent Inflammation in Men With Non-odontogenic Abscesses of the Neck.

Introduction If non-odontogenic abscesses and phlegmons (all purulent inflammations where the etiology is not a diseased tooth) of the neck are not promptly treated, they can lead to serious complications and even end in the death of the affected patient. Classical markers of inflammation such as plasma concentration of leukocytes (WBC), neutrophils (Neu), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are elevated in inflammatory neck diseases, but none of them has been proven as a definite marker in the prediction of this type of pathology. This necessitates the search and analysis of new indicators that could be used in the diagnosis, follow-up, and prognosis of patients with purulent neck infections. Potentially, such a marker could be the delta neutrophil index (DNI), which is increasingly entering clinical practice as a prognostic indicator in critically ill patients with life-threatening illnesses, including sepsis and systemic inflammatory response syndrome (SIRS). In the world literature, there are no data that have been studied in patients with purulent diseases of the neck of non-odontogenic origin, which is the aim of this original article. Materials and methods This retrospective study included 40 men with an average age of 46 (18-87) years with non-odontogenic abscesses and phlegmons of the neck who were hospitalized and operated on. In all of them, the concentration of leukocytes, eosinophils (Eo), neutrophils, and mature polymorphonuclear neutrophil leukocytes (PMN) was examined on an automatic 5-Diff hematology analyzer, ADVIA 2120i (SiemensMedical Solutions USA, Malvern, PA). Thus, it was calculated according to the formula for calculating DNI (DNI% = (Neu%+Eo%) - PMN%). Retrospectively, 30 healthy men with an average age of 42 (18-81) years were used as a control group, in which the same indicators were examined during a preventive examination. Results and discussion Comparing the mean values of WBC, Neu, and DNI between the studied patients with non-odontogenic purulent neck infections (n=40) and the healthy male controls (n=30) it was found that all three indicators of inflammation are significantly higher in the ill men, and these differences are statistically significant (p<0.05): 10.19 ±2.68x103/L versus 7.37 ±1.93x103/L for leukocytes, 7.68 ±2, 76x103/L versus 4.13 ±1.48x103/L for neutrophils, and 1.11±0.83% versus -1.07±1.22% for DNI. Therefore, the high mean numbers of measured WBC and Neu in men with non-odontogenic purulent neck infections were associated with an increase in their mean calculated DNI. This gives us reason to think that while WBC and Neualone are not sufficient for definitive diagnosis, treatment follow-up, and prediction of disease outcome, in combination with DNI they become reliable indicators in purulent neck infections. Conclusions The DNI correlates well with other well-known and established indicators of inflammation, such as the concentration of leukocytes and neutrophils in the peripheral blood of patients. Its calculation is fast as an implementation procedure and is economically beneficial. Its independent use in the diagnosis and treatment of these diseases is about to be investigated and analyzed.

Experience of management of pediatric upper gastrointestinal perforations: a series of 30 cases.

This study aimed to explore the characteristics of pediatric upper gastrointestinal (UGI) perforations, focusing on their diagnosis and management. Between January 2013 and December 2021, 30 children with confirmed UGI perforations were enrolled, and their clinical data were analyzed. Two groups were compared according to management options, including open surgical repair (OSR) and laparoscopic/gastroscopic repair (LR). A total of 30 patients with a median age of 36.0 months (1 day-17 years) were included in the study. There were 19 and 11 patients in the LR and OSR groups, respectively. In the LR group, two patients were treated via exploratory laparoscopy and OSR, and the other patients were managed via gastroscopic repair. Ten and three patients presented the duration from symptom onset to diagnosis within 24 h (p = 0.177) and the number of patients with hemodynamically unstable perforations was 4 and 3 in the LR and OSR groups, respectively. Simple suture or clip closure was performed in 27 patients, and laparoscopically pedicled omental patch repair was performed in two patients. There was no significant difference in operative time and length of hospital stay between the LR and OSR groups. Treatment failed in two patients because of severe sepsis and multiple organ dysfunction syndrome, including one with fungal peritonitis. Surgery for pediatric UGI perforations should be selected according to the general status of the patient, age of the patient, duration from symptom onset, inflammation, and perforation site and size. Antibiotic administration and surgical closure remain the main strategies for pediatric UGI perforations.

Approach to red blood cell transfusions in post-operative congenital heart disease surgery patients: when to stop?

The best transfusion approach for CHD surgery is controversial. Studies suggest two strategies: liberal (haemoglobin ≤ 9.5 g/dL) and restrictive (waiting for transfusion until haemoglobin ≤ 7.0 g/dL if the patient is stable). Here we compare liberal and restrictive transfusion in post-operative CHD patients in a cardiac intensive care unit. Retrospective analysis was conducted on CHD patients who received liberal transfusion (2019-2021, n=53) and restrictive transfusion (2021-2022, n=43). The two groups were similar in terms of age, gender, Paediatric Risk of Mortality-3 score, Paediatric Logistic Organ Dysfunction-2 score, Risk Adjustment for Congenital Heart Surgery-1 score, cardiopulmonary bypass time, vasoactive inotropic score, total fluid balance, mechanical ventilation duration, length of cardiac intensive care unit stay, and mortality. The liberal transfusion group had a higher pre-operative haemoglobin level than the restrictive group (p < 0.05), with no differences in pre-operative anaemia. Regarding the minimum and maximum post-operative haemoglobin levels during a cardiac intensive care unit stay, the liberal group had higher haemoglobin levels in both cases (p<0.01 and p=0.019, respectively). The number of red blood cell transfusions received by the liberal group was higher than that of the restrictive group (p < 0.001). There were no differences between the two groups regarding lactate levels at the time of and after red blood cell transfusion. The incidence of bleeding, re-operation, acute kidney injury, dialysis, sepsis, and systemic inflammatory response syndrome was similar. Restrictive transfusion may be preferable over liberal transfusion. Achieving similar outcomes with restrictive transfusions may provide promising evidence for future studies.

ExpertNet: A Deep Learning Approach to Combined Risk Modeling and Subtyping in Intensive Care Units.

Risk models play a crucial role in disease prevention, particularly in intensive care units (ICUs). Diseases often have complex manifestations with heterogeneous subpopulations, or subtypes, that exhibit distinct clinical characteristics. Risk models that explicitly model subtypes have high predictive accuracy and facilitate subtype-specific personalization. Such models combine clustering and classification methods but do not effectively utilize the inferred subtypes in risk modeling. Their limitations include tendency to obtain degenerate clusters and cluster-specific data scarcity leading to insufficient training data for the corresponding classifier. In this article, we develop a new deep learning model for simultaneous clustering and classification, ExpertNet, with novel loss terms and network training strategies that address these limitations. The performance of ExpertNet is evaluated on the tasks of predicting risk of (i) sepsis and (ii) acute respiratory distress syndrome (ARDS), using two large electronic medical records datasets from ICUs. Our extensive experiments show that, in comparison to state-of-the-art baselines for combined clustering and classification, ExpertNet achieves superior accuracy in risk prediction for both ARDS and sepsis; and comparable clustering performance. Visual analysis of the clusters further demonstrates that the clusters obtained are clinically meaningful and a knowledge-distilled model shows significant differences in risk factors across the subtypes. By addressing technical challenges in training neural networks for simultaneous clustering and classification, ExpertNet lays the algorithmic foundation for the future development of subtype-aware risk models.

Trauma-Induced Systemic Inflammatory Response: A Comprehensive Review

Trauma is a noteworthy contributor to death and disability in adults. Its impact can extend to multiple organ systems via complex physiological reactions. This article comprehensively examines the physiological responses that transpire following trauma. It begins with the initial immune and inflammatory responses and advances to the possibility of sepsis and multi-organ dysfunction syndrome (MODS). The article delves into the roles of the innate and adaptive immune systems, the Systemic Inflammatory Response Syndrome (SIRS), and the various stages of sepsis. It emphasizes the importance of early detection and treatment, showcasing the benefit of the Injury Severity Score (ISS) to assess trauma severity and the Sequential Organ Failure Assessment (SOFA) scores to estimate sepsis severity. While acknowledging progress in understanding and identifying trauma-related conditions, the article emphasizes the importance of providing timely and accurate treatment to improve patient’s recovery.

B-075 Biophysical Changes of Leukocyte Activation (and NETosis) in the Cellular Host Response to Sepsis

Abstract Background During sepsis, neutrophils, upon activation, undergo biophysical and biochemical changes that may terminate in the release of neutrophil extracellular traps (NETs) (1–3). The IntelliSep test is a rapid sepsis diagnostic that assesses immune activation by quantifying biophysical properties of leukocytes from whole blood in &amp;lt;10 minutes. The test results in the IntelliSep Index (ISI), ranging between 0.1–10.0, stratified into three interpretation bands (Band 1, Band 2, and Band 3) based on the probability of the clinical syndrome of sepsis (4, 5). We investigated the correlation between the IntelliSep result and immunological changes observed during leukocyte activation through in-vitro studies and using clinical samples from non-septic and septic patients. Methods In-vitro Studies: Healthy blood samples were collected between April - August 2022 from 18 volunteers at a blood donor center. Aliquots of each blood sample were incubated for 10 minutes with phorbol myristate acetate (PMA) in phosphate-buffered saline at one of 3 concentrations: 0, 200, and 400 nM prior to the IntelliSep test (3 repeats per donor per concentration). Clinical Studies: Subjects with signs or symptoms of infection were enrolled from Emergency Departments (EDs) in three similar but distinct prospective cohort studies (February 2016—September 2019) (1, 2). The IntelliSep test was performed on a aliquot of fresh whole blood from each subject, and remnant plasma was prepared and frozen for later analysis. Plasma levels of neutrophil elastase-DNA (NE DNA) and citrullinated histone H3-DNA (Cit-H3 DNA) complexes were quantified using previously reported custom ELISAs 3,6. Subjects were retrospectively adjudicated as sick (adjudicated as septic with SOFA scores peaking on the day of enrollment compared to two subsequent days) and “healthy” (SOFA for day of enrollment &amp;lt;2, hospital length of stay &amp;lt;3 days). Results Significant increases in ISI scores were observed with increasing concentration of PMA in healthy blood samples (0 and 200: P &amp;lt; 10−10; 0 and 400: P &amp;lt; 10−10). The clinical analysis cohort consisted of 39 “sick” and 42 “healthy” subjects. Linear correlation was observed between the ISI and NE DNA and Cit-H3 DNA quantities with significant increases across ISI Interpretation Bands (Band 1 to Band 3: P &amp;lt; 0.001). Conclusion Correlation of increasing ISI and PMA concentration supports the hypothesis that the biophysical changes measured by the IntelliSep test result from leukocyte activation. Observed correlation between the ISI and NET quantities suggest that NET formation is one of the activation pathways that result in the biophysical changes measured in the ISI. Together these experiments support that biophysical changes of leukocyte activation measured using a cellular host response test could provide a window into a patient’s state of dysregulated immunity and may have the potential to aid ED physicians in timely diagnosis of sepsis.

The Effect of Therapeutic Hypothermia on Prognosis in Patients Receiving Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) is a commonly used therapeutic modality in the pediatric intensive care unit (PICU) for the treatment of severe acute kidney injury, as well as for addressing metabolic abnormalities, fluid-electrolyte imbalances, and acid-base disorders. According to reports, therapeutic hypothermia treatment has demonstrated the ability to decrease cellular metabolism, oxygen consumption, formation of free radicals, cell death, and inflammatory signals. The study encompassed all individuals who underwent CRRT at both Manisa City Hospital and Manisa Celal Bayar University Hospital throughout the period from February 2021 to November 2022. A total of 14 patients who received CRRT were subjected to a warming procedure utilizing an external blanket and an external heater attached to the CRRT venous return line, resulting in the attainment of a body temperature exceeding 36°C. Therapeutic hypothermia was implemented on 12 patients to maintain their body temperature within the range of 32-35°C. The study population exhibited a median age of 24.5 months, with males comprising 61.5% of the sample. A therapeutic hypothermia treatment was administered to a cohort of 12 patients. The patients who had therapeutic hypothermia exhibited a significantly reduced vasoactive-inotropic score (p = 0.038). Patients who did not receive therapeutic hypothermia exhibited a prolonged need for mechanical ventilation (p = 0.020). The duration of stay in the PICU for patients who underwent therapeutic hypothermia was shown to be considerably shorter compared to those who did not receive therapeutic hypothermia (p = 0.047). The potential efficacy of moderate therapeutic hypothermia appears promising, particularly in the context of patients who are receiving CRRT for severe sepsis and acute respiratory distress syndrome. This is attributed to the anti-inflammatory properties and hypometabolic effects associated with this intervention. To the best of our current understanding, this study represents the initial investigation showcasing the effectiveness of combining therapeutic hypothermia with CRRT in the pediatric population.