Cases Of Sepsis Research Articles

Sepsis, Antimicrobial Resistance, and Alternative Therapies

Sepsis, a life-threatening condition caused by the body's excessive response to an infection, has emerged as a global health menace. Around 20% of all global deaths are attributable to sepsis. Conversely, the presence of antimicrobial resistance (AMR) poses a significant peril to the health system. AMR constitutes an escalating pandemic that we must not disregard, as the absence of effective antibiotics would compromise the treatment of even commonplace bacterial infections. Therefore, the increasing prevalence of AMR further adds complexity to the management and outcomes of individuals with sepsis. AMR plays a contributory role in aggravating the consequences of sepsis, ranging from prolonged hospitalization to mortality. The World Health Organization (WHO) has prioritized AMR as a major concern necessitating immediate action to prevent dire consequences in the future. Though, One Health approach, infection prevention, rational use of antibiotics, strengthening surveillance systems, as well as research and development, are crucial strategies in combating antimicrobial resistance, alternative therapies, such as phage therapy and immunotherapeutics, are being explored for the management of AMR infections. Advances in these therapies show promise in addressing the challenges posed by antibiotic resistance in treating sepsis. In this critical assessment, we succinctly delineate the existing challenges of AMR in managing sepsis cases, and we provide an overview of the advancements in treating sepsis through alternative therapeutic modalities.

Applying Machine Learning to Blood Count Data Predicts Sepsis with ICU Admission.

Timely diagnosis is crucial for sepsis treatment. Current machine learning (ML) models suffer from high complexity and limited applicability. We therefore created an ML model using only complete blood count (CBC) diagnostics. We collected non-intensive care unit (non-ICU) data from a German tertiary care centre (January 2014 to December 2021). Using patient age, sex, and CBC parameters (haemoglobin, platelets, mean corpuscular volume, white and red blood cells), we trained a boosted random forest, which predicts sepsis with ICU admission. Two external validations were conducted using data from another German tertiary care centre and the Medical Information Mart for Intensive Care IV database (MIMIC-IV). Using the subset of laboratory orders also including procalcitonin (PCT), an analogous model was trained with PCT as an additional feature. After exclusion, 1 381 358 laboratory requests (2016 from sepsis cases) were available. The CBC model shows an area under the receiver operating characteristic (AUROC) of 0.872 (95% CI, 0.857-0.887). External validations show AUROCs of 0.805 (95% CI, 0.787-0.824) for University Medicine Greifswald and 0.845 (95% CI, 0.837-0.852) for MIMIC-IV. The model including PCT revealed a significantly higher AUROC (0.857; 95% CI, 0.836-0.877) than PCT alone (0.790; 95% CI, 0.759-0.821; P < 0.001). Our results demonstrate that routine CBC results could significantly improve diagnosis of sepsis when combined with ML. The CBC model can facilitate early sepsis prediction in non-ICU patients with high robustness in external validations. Its implementation in clinical decision support systems has strong potential to provide an essential time advantage and increase patient safety.

Serum Resistin as a Potential Mortality Predictor in Neonatal Sepsis.

Aim The aim of this study was to investigate the utility of serum resistin levels as a prognostic indicator for mortality in neonates diagnosed with sepsis. Methodology This one-year prospective study at Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences (PGIMS), Rohtak, India, included 151 neonates categorized into two groups based on blood culture results: group 1 (n=86) included those with culture-negative, probable sepsis and group 2 (n=65) included those with culture-positive, proven sepsis. Blood samples obtained pre-treatment underwent comprehensive analysis, including complete blood count, C-reactive protein assessment, micro-erythrocyte sedimentation rate, and resistin level measurement via enzyme-linked immunosorbent assay. The comparison between groups was conducted using either the Student t-test or the Mann-Whitney U test, while correlations were assessed using the Spearman correlation. These analyses were employed to identify the optimal resistin cut-off for distinguishing patients with sepsis. A p-value of <0.05 was considered statistically significant. Results This study with 151 neonates diagnosed with sepsis found a significant association (p < 0.05) between elevated serum resistin levels and increased mortality risk. Multivariate analysis confirmed an independent predictive role of resistin. Elevated resistin levels correlate with higher chances of requiring mechanical ventilation and prolonged hospital stays. These findings highlight serum resistin's potential as a prognostic tool for the early identification of high-risk neonatal sepsis patients. Conclusion This study highlights the link between elevated serum resistin levels and increased mortality risk in neonatal sepsis, supported by strong multivariate analysis, indicating an independent predictive role. Additionally, resistin correlates with higher chances of mechanical ventilation and prolonged hospitalization, suggesting its potential as a prognostic marker for early identification of high-risk neonatal sepsis cases.

CLINICAL OBSERVATION OF TREATMENT EFFICACY IN SEPSIS: A PROSPECTIVE STUDY

Objective: To examine the safety and efficacy associated with various treatment approaches and to identify trends and variations in the management of severe sepsis, including the usage of antibiotics, and supportive care. To examine factors associated with improved or worsened outcomes in severe sepsis cases, such as patient demographics, comorbidities, or timing of treatment. Design: A hospital-based prospective study was done on all inpatients and outpatients in Princess DurruShehvar Childrens &amp; General Hospital, Hyderabad, Telangana for 6 months. Methods: The data collection form and patient consent form were designed for this study. It comprises information regarding the study subjects data such as demographics, medical and medication history, laboratory investigations, diagnosis, present prescribed medication, and progress chart. Investigators collected the relevant data and recorded it in data collection form. The prescription will be selected based on inclusion criteria and exclusion criteria. The data obtained was compiled and analysed using appropriate statistical tests. Quantitative variables were summarized using descriptive studies (percentages, mean, standard deviation, number of observations). The data was statistically analyzed using spss and pair t test, graphs, pie diagrams, and bar graphs. Results A total of 115 patients were included in this prospective study and 60% of them show culture sensitivity. Meropenem was found to be the most potent antibiotic. The analysis of the treatments impact reveals noteworthy outcomes across multiple parameters. The intervention demonstrates a significant effect in reducing systolic blood pressure, although no major influence on diastolic blood pressure is observed. Regarding erythrocyte sedimentation rate (ESR), a substantial and statistically significant decrease is indicated post-treatment. Notably, arterial blood gas (ABG) levels exhibit a considerable difference pre- and post-treatment, with a p-value below 0.05, suggesting a rejection of the null hypothesis. Additionally, the treatment is associated with a significant increase in total leukocyte counts, as evidenced by the positive mean difference and a 95% confidence interval entirely above zero. These findings underscore the diverse impacts of the treatment on various physiological markers. Conclusion Prospective sepsis treatment studies offer a nuanced grasp of real-world effectiveness, linking controlled experiments to clinical reality. Despite biases, they contribute to evidence-based strategies, acknowledging clinical complexities. This practical approach guides healthcare professionals with adaptable, patient-centered methods. Emphasis on rigorous statistical methodologies enhances comprehension. Integrating observational and experimental data enriches our understanding of sepsis management. Overall, these studies shape holistic approaches for effective treatment.

Raise the Flag II: sepsis mortality before and after the introduction of a whole-of-system quality improvement programme at a tertiary hospital in New Zealand.

To study in-patient mortality before and after the introduction of a whole-of-system sepsis quality improvement programme at a tertiary hospital in New Zealand. The "Raise the Flag" sepsis quality improvement programme was launched in 2018. Discharge coding data were used to identify sepsis cases between May 2015 and July 2021. Of 4,268 cases of sepsis identified, 81% were over 55 years old, 34% were of Māori or Pacific Island ethnicity, 61% had significant co-morbid illness and over two thirds (68%) lived in the two highest quintiles of socio-economic deprivation. The adjusted odds of in-patient mortality were lower in the post-launch period (adjusted odds ratio [aOR] 0.83, 95% confidence interval [CI] 0.7-0.98, p<0.05), and were higher in association with age (aOR 1.04 for every additional year of age, 95% CI 1.03-1.05, p<0.01), socio-economic status (aOR 1.47 comparing the highest quintile of socio-economic deprivation with the lowest, 95% CI 1.06-2.04, p=0.02) and comorbidity (aOR 2.42 comparing a comorbidity score of 1 with a score of 0, 95% CI 2.1-3.52, p<0.01). In patients with a sepsis diagnosis, the odds of in-patient death were lower following the launch of the Raise the Flag sepsis quality improvement programme.

A study of level of procalcitonin as marker of early onset sepsis in neonates

Background: Neonatal sepsis is one of the commonest causes of morbidity and mortality. It is one of the four leading causes of morbidity and mortality in India. The purpose of this study was to evaluate the levels of procalcitonin as a rapid diagnostic test, to identify those with infection as soon as possible, and to classify them into definitive, clinical, or no sepsis. The rise in Procalcitonin levels in the neonate with sepsis is very rapid. Hence, it can be used for the diagnosis of early onset neonatal sepsis. Objectives were to estimate the concentration of Procalcitonin for diagnosis of early onset neonatal sepsis and to compare the Procalcitonin levels amongst 3 categories of neonatal sepsis (definite, clinical and no sepsis). Methods: This is a hospital based analytical prospective study. Results: 104 babies with early onset sepsis were included in the study from the NICU in tertiary health care center. Procalcitonin is positive in 69 (66.35%) and negative in 35 (33.65%). Out of the total 69 neonates with Procalcitonin positive, 42 (60.8%) neonates are preterm and 27 (39.1%) are term neonates. Out of the total 35 neonates with Procalcitonin negative, 24 (68.5%) neonates are preterm and 11 (31.4%) are term neonates. There was no sepsis observed in 57 (54.8%) of cases, clinical sepsis was observed in 34 (32.6%) of cases and definite sepsis was observed in 13 (12.5%). The mean value of level of Procalcitonin in different categories of sepsis as determined from the data is 3.27 ng/ml in cases of No sepsis, 11.79 ng/ml in cases of clinical sepsis and 17.2 ng/ml in cases of definitive sepsis. Conclusions: Procalcitonin has good sensitivity and hence can detect most cases of neonatal sepsis and good negative predictive value. Procalcitonin contributes more significantly to the diagnosis of newborn septicemia when paired with additional testing and helps in identifying the categories of sepsis in neonates.

Validation of SeptiCyte RAPID to Discriminate Sepsis from Non-Infectious Systemic Inflammation.

(1) Background: SeptiCyte RAPID is a molecular test for discriminating sepsis from non-infectious systemic inflammation, and for estimating sepsis probabilities. The objective of this study was the clinical validation of SeptiCyte RAPID, based on testing retrospectively banked and prospectively collected patient samples. (2) Methods: The cartridge-based SeptiCyte RAPID test accepts a PAXgene blood RNA sample and provides sample-to-answer processing in ~1 h. The test output (SeptiScore, range 0-15) falls into four interpretation bands, with higher scores indicating higher probabilities of sepsis. Retrospective (N = 356) and prospective (N = 63) samples were tested from adult patients in ICU who either had the systemic inflammatory response syndrome (SIRS), or were suspected of having/diagnosed with sepsis. Patients were clinically evaluated by a panel of three expert physicians blinded to the SeptiCyte test results. Results were interpreted under either the Sepsis-2 or Sepsis-3 framework. (3) Results: Under the Sepsis-2 framework, SeptiCyte RAPID performance for the combined retrospective and prospective cohorts had Areas Under the ROC Curve (AUCs) ranging from 0.82 to 0.85, a negative predictive value of 0.91 (sensitivity 0.94) for SeptiScore Band 1 (score range 0.1-5.0; lowest risk of sepsis), and a positive predictive value of 0.81 (specificity 0.90) for SeptiScore Band 4 (score range 7.4-15; highest risk of sepsis). Performance estimates for the prospective cohort ranged from AUC 0.86-0.95. For physician-adjudicated sepsis cases that were blood culture (+) or blood, urine culture (+)(+), 43/48 (90%) of SeptiCyte scores fell in Bands 3 or 4. In multivariable analysis with up to 14 additional clinical variables, SeptiScore was the most important variable for sepsis diagnosis. A comparable performance was obtained for the majority of patients reanalyzed under the Sepsis-3 definition, although a subgroup of 16 patients was identified that was called septic under Sepsis-2 but not under Sepsis-3. (4) Conclusions: This study validates SeptiCyte RAPID for estimating sepsis probability, under both the Sepsis-2 and Sepsis-3 frameworks, for hospitalized patients on their first day of ICU admission.

Time to Positivity of Blood Culture as a Predictor of Causative Pathogens and Survival in Neonatal Sepsis: A Retrospective Cohort Study from Indonesia.

In the blood culture procedure for neonatal sepsis, time to positivity (TTP) reflects the pathogenic bacterial load and the time required for empirical antibiotic regimen administration prior to definitive treatment. This study aims to identify the differences in TTP among causative pathogens and its predictive value for the overall survival of neonates with sepsis at a tertiary healthcare center in Indonesia. A retrospective cohort study was conducted from January 2020 to August 2022 at Dr. Soetomo General Hospital, Surabaya, Indonesia. Neonates with blood culture-proven neonatal sepsis were included in the analysis. TTP was defined as the time between the acceptance of a blood culture specimen from the neonatal intensive care unit and reports of positive culture growth by the laboratory. Across 125 cases, the median TTP was 58.1 hours (IQR = 24.48). Blood cultures were positive within 48 hours for 41.6% of cases, 72 hours for 86.4%, and 96 hours for 98.4%. A significantly shorter TTP was exhibited by the three major gram-negative organisms (Klebsiella pneumoniae,Acinetobacter baumannii,Enterobacter cloacae) compared to coagulase-negative Staphylococci. The neonatal sepsis mortality rate was 49.6% during the study period. In the Cox multivariate regression model, a shorter TTP was an independently predicted mortality in the entire cohort (hazard ratio (HR) = 0.985, 95% CI: 0.973-0.998) and the gram-negative sepsis cohort group (HR = 0.983, 95% CI: 0.968-0.999). TTP predicts different causative pathogens and the overall survival of neonatal sepsis cases at a tertiary healthcare facility in Indonesia.

Diagnostic Values of Blood Indices for Neonatal Sepsis

Background: Sepsis is the leading cause of death in newborns, particularly in underdeveloped countries. Early diagnosis and appropriate treatment are critical in reducing neonatal mortality. Since blood culture results are often unavailable for 48 - 72 hours, other hematologic findings may provide useful information for early diagnosis. Objectives: We examined the relationship between neonatal sepsis and blood indices in order to achieve early diagnosis. Methods: In this hospital-based retrospective multiple-event case-control study, we allocated the neonates into three groups: Culture-positive sepsis, culture-negative sepsis, and neonates without sepsis. We compared the lab data within these three groups. Results: The study included 319 neonates: 209 cases of culture-positive sepsis, 65 cases of culture-negative sepsis, and 45 cases without neonatal sepsis. Pearson's test demonstrated a significant correlation between thrombocytopenia, positive C-reactive protein (CRP), and high cell distribution width with culture-positive sepsis (P = 0.000), indicating a statistical difference between the three groups. The mean CRP and eosinophil levels were higher in the culture-positive group with fungal sepsis. Conclusions: In septic neonates with high CRP levels, particularly in conjunction with eosinophilia, fungal coverage should be considered.

Assessment of the prevalence of meningitis in clinically suspected cases of early and late onset neonatal sepsis

Background: Meningitis is more common in the neonatal period than any other time in life and is an important cause of morbidity and mortality globally. In India, rate of neonatal sepsis is reported 0.5 per 1000 live births. The major burden of neonatal sepsis and meningitis occurs in the developing world. According to WHO estimates there are approximately 5 million neonatal deaths in a year. The objective of the study is to assess the prevalence of meningitis in neonates with clinical suspicion of sepsis. Methods: The study was conducted among suspected cases of neonatal septicemia in neonatal intensive care unit (NICU), department of pediatrics, VPIMS, Lucknow. It is a prospective observational study. A total of 180 neonates were included in the study. Results: Out of 180 neonates, CSF examination of 131 (72.78%) neonates was normal, of 37 (20.56%) was suggestive of meningitis. Prevalence of meningitis in neonatal sepsis was 20.0%. It was 18.0% in early neonatal sepsis and 32.6% in late neonatal sepsis cases. Conclusions: The findings of present study suggested that there is a high risk of meningitis among neonatal sepsis cases. Cases with risk factors like twin birth, anemia, low TLC, low platelet count, acid-base imbalance and X-ray findings suggestive of pneumonitis should be kept in a high-risk category.

Sepsis Prediction at Emergency Department Triage Using Natural Language Processing: Retrospective Cohort Study.

Despite its high lethality, sepsis can be difficult to detect on initial presentation to the emergency department (ED). Machine learning-based tools may provide avenues for earlier detection and lifesaving intervention. The study aimed to predict sepsis at the time of ED triage using natural language processing of nursing triage notes and available clinical data. We constructed a retrospective cohort of all 1,234,434 consecutive ED encounters in 2015-2021 from 4 separate clinically heterogeneous academically affiliated EDs. After exclusion criteria were applied, the final cohort included 1,059,386 adult ED encounters. The primary outcome criteria for sepsis were presumed severe infection and acute organ dysfunction. After vectorization and dimensional reduction of triage notes and clinical data available at triage, a decision tree-based ensemble (time-of-triage) model was trained to predict sepsis using the training subset (n=950,921). A separate (comprehensive) model was trained using these data and laboratory data, as it became available at 1-hour intervals, after triage. Model performances were evaluated using the test (n=108,465) subset. Sepsis occurred in 35,318 encounters (incidence 3.45%). For sepsis prediction at the time of patient triage, using the primary definition, the area under the receiver operating characteristic curve (AUC) and macro F1-score for sepsis were 0.94 and 0.61, respectively. Sensitivity, specificity, and false positive rate were 0.87, 0.85, and 0.15, respectively. The time-of-triage model accurately predicted sepsis in 76% (1635/2150) of sepsis cases where sepsis screening was not initiated at triage and 97.5% (1630/1671) of cases where sepsis screening was initiated at triage. Positive and negative predictive values were 0.18 and 0.99, respectively. For sepsis prediction using laboratory data available each hour after ED arrival, the AUC peaked to 0.97 at 12 hours. Similar results were obtained when stratifying by hospital and when Centers for Disease Control and Prevention hospital toolkit for adult sepsis surveillance criteria were used to define sepsis. Among septic cases, sepsis was predicted in 36.1% (1375/3814), 49.9% (1902/3814), and 68.3% (2604/3814) of encounters, respectively, at 3, 2, and 1 hours prior to the first intravenous antibiotic order or where antibiotics where not ordered within the first 12 hours. Sepsis can accurately be predicted at ED presentation using nursing triage notes and clinical information available at the time of triage. This indicates that machine learning can facilitate timely and reliable alerting for intervention. Free-text data can improve the performance of predictive modeling at the time of triage and throughout the ED course.

Sepsis in Latvia-Incidence, Outcomes, and Healthcare Utilization: A Retrospective, Observational Study.

This study explores the incidence, outcomes, and healthcare resource utilization concerning sepsis in Latvia's adult population. Using a merged database from the National Health Service and the Latvian Centre for Disease Prevention and Control, sepsis-related hospitalizations were analyzed from 2015-2020. Findings revealed a 53.1% surge in sepsis cases from 2015-2018 with subsequent stabilization. This spike was more prominent among elderly patients. The age/sex adjusted case fatality rate rose from 34.7% in 2015 to 40.5% in 2020. Of the 7764 sepsis survivors, the one-year mortality rate was 12% compared to 2.2% in a reference group of 20,686 patients with infections but no further signs of sepsis. Sepsis survivors also incurred higher healthcare costs, driven by longer rehospitalizations and increased pharmaceutical needs, though they accessed outpatient services less frequently than the reference group. These findings underscore the growing detection of sepsis in Latvia, with survivors facing poorer outcomes and suggesting the need for enhanced post-sepsis outpatient care.

Sepsis Stewardship: The Puzzle of Antibiotic Therapy in the Context of Individualization of Decision Making.

The main recent change observed in the field of critical patient infection has been universal awareness of the need to make better use of antimicrobials, especially for the most serious cases, beyond the application of simple and effective formulas or rigid protocols. The increase in resistant microorganisms, the quantitative increase in major surgeries and interventional procedures in the highest risk patients, and the appearance of a significant number of new antibiotics in recent years (some very specifically directed against certain mechanisms of resistance and others with a broader spectrum of applications) have led us to shift our questions from "what to deal with" to "how to treat". There has been controversy about how best to approach antibiotic treatment of complex cases of sepsis. The individualized and adjusted dosage, the moment of its administration, the objective, and the selection of the regimen are pointed out as factors of special relevance in a critically ill patient where the frequency of resistant microorganisms, especially among the Enterobacterales group, and the emergence of multiple and diverse antibiotic treatment alternatives have made the appropriate choice of antibiotic treatment more complex, requiring a constant updating of knowledge and the creation of multidisciplinary teams to confront new infections that are difficult to treat. In this article, we have reviewed the phenomenon of the emergence of resistance to antibacterials and we have tried to share some of the ideas, such as stewardship, sparing carbapenems, and organizational, microbiological, pharmacological, and knowledge tools, that we have considered most useful and effective for individualized decision making that takes into account the current context of multidrug resistance. The greatest challenge, therefore, of decision making in this context lies in determining an effective, optimal, and balanced empirical antibiotic treatment.

A prospective observational study of sepsis-associated coagulopathy (SAC) in septic shock in the pediatric intensive care unit of tertiary care hospital in central rural India

Background: Sepsis-associated coagulopathy (SAC) is a frequently encountered clinical scenario in pediatric critical care practice. The disruptions within the normal coagulation cascade in cases of sepsis significantly impact the ultimate patient outcome. Objective: This study aims to evaluate the associations between sepsis-associated coagulopathy (SAC) in pediatric septic shock cases and their corresponding clinical outcomes. Methods: This study will be conducted within a tertiary care Pediatric Intensive Care Unit (PICU), focusing on children aged one month to 18 years who have been admitted to manage sepsis. Cases diagnosed with sepsis will undergo evaluation and treatment according to the established PICU protocol. Coagulation profiles, encompassing International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), Prothrombin Time (PT), and platelet counts, will be subjected to analysis. Any deviations in coagulation parameters will be compared and correlated with morbidity and mortality outcomes. Expected results: This study will establish correlations between the severity of sepsis and its subsequent outcomes, specifically concerning aberrations in coagulation profile levels. A meticulous analysis will focus on critically ill cases necessitating various interventions and exhibiting deviant coagulation patterns. Conclusions: This research aims to unravel potentially pivotal prognostic correlations within sepsis cases. The coagulation profile, a standard investigation, can be a predictive tool for outcomes within the Pediatric Intensive Care Unit (PICU).

Multidrug-Resistant Acinetobacter and Enterobacterales Causing Neonatal Sepsis at a Tertiary Healthcare Facility in Indonesia

Introduction: Increasing resistance to multiple classes of antimicrobials, leading to multidrug resistance (MDR), provides a major challenge for the management of bloodstream infections in the neonatal intensive care unit (NICU). The dissemination of Acinetobacter and Enterobacterales species were of great importance owing to their high prevalence and resistance against a broad spectrum of available antimicrobials, thereby exacerbating the prognosis for afflicted patients. This study aimed to highlight neonatal sepsis cases caused by MDR Acinetobacter and Enterobacterales in the NICU of a tertiary healthcare center in Surabaya, Indonesia. Methods: This retrospective cohort study was conducted in Dr. Soetomo General Hospital, Surabaya, from January 2020 to August 2022. Documented cases of neonatal sepsis were identified from electronic medical records under the ICD-10 P36 code. Continuous monitoring of blood culture was performed following the initial suspicion of sepsis, complemented with semiautomated antimicrobial susceptibility testing. Results: A total of 75 out of 125 culture-proven neonatal sepsis cases were reported caused by Acinetobacter baumannii ( n = 19; 15.2%) and Enterobacterales ( n = 56; 44.8%) species. These organisms exhibited the MDR rates of 78.9% and 91.1%, respectively. Klebsiella pneumoniae ( K. pneumoniae) emerged as the predominant Enterobacterales, demonstrating an MDR rate of 92.1%. Possible extensively- and possible pan-drug-resistant organisms were also identified at a concerning rate in Acinetobacter (73.7% and 21.1%, respectively) and Enterobacterales (28.6% and 1.8%, respectively). The susceptibility of Acinetobacter to carbapenems was notably low (26.3%), whereas Enterobacterales exhibited a relatively higher susceptibility rate (75%). Notably, 9 and 37 documented deaths were associated with neonatal sepsis because of MDR Acinetobacter and Enterobacterales, respectively. Lower birth weight and shorter length of NICU stay were significantly related to mortality in neonatal sepsis. Conclusion: The alarming rate of MDR underscores further investigations on the extent of inappropriate antibiotic usage in the unit, particularly concerning neonates requiring invasive medical interventions and those with foundational clinical risk factors.

The unfolded protein response pathway as a possible link in the pathogenesis of COVID-19 and sepsis.

The global impact of the COVID-19 pandemic has been substantial. Emerging evidence underscores a strong clinical connection between COVID-19 and sepsis. Numerous studies have identified the unfolded protein response (UPR) pathway as a crucial pathogenic pathway for both COVID-19 and sepsis, but it remains to be investigated whether this signaling pathway operates as a common pathogenic mechanism for both COVID-19 and sepsis. In this study, single-cell RNA-seq data and transcriptome data for COVID-19 and sepsis cases were downloaded from GEO (Gene Expression Omnibus). By analyzing the single-cell transcriptome data, we identified B cells as the critical cell subset and the UPR pathway as the critical signaling pathway. Based on the transcriptome data, a machine learning diagnostic model was then constructed using the interleaved genes of B-cell-related and UPR-pathway-related genes. We validated the diagnostic model using both internal and external datasets and found the accuracy and stability of this model to be extremely strong. Even after integrating our algorithmic model with the patient's clinical status, it continued to yield identical results, further emphasizing the reliability of this model. This study provides a novel molecular perspective on the pathogenesis of sepsis and COVID-19 at the single-cell level and suggests that these two diseases may share a common mechanism.

Pathogen-wise Clinical Profile, Outcome and Antibiotic Sensitivity Profile of Septic Newborns in Level III Neonatal Intensive Care Unit of a Tertiary Teaching Hospital: A Retrospective Study

Introduction: Culture positive sepsis remains to be a leading cause of death in Neonatal Intensive Care Unit (NICU) mainly among preterm and low birth weight newborns. The objective was to analyze the initial signs of sepsis, antibiotic sensitivity, and outcome of septic newborns in NICU. Methods: The demographic data, initial clinical features at suspicion of sepsis, diagnosis, laboratory abnormalities, pathogen isolated and antibiotic sensitivity patterns of the septic neonates, and their outcome were documented from their case records. Results: A total of 161 culture positive septic newborns, 76.4% were preterm and 54 died of sepsis (33.54%). Early and late onset sepsis was seen in 56 and 109 neonates, respectively. The initial clinical findings at suspicion of sepsis which had a statistical significance were tachycardia in Escherichia coli and Pseudomonas sepsis, hyperglycemia in Burkholderia, fever in Candida, sclerema in Klebsiella pneumoniae (KP), and seizures in E. coli sepsis. The cerebrospinal fluid culture positive newborns commonly presented with apnea, poor perfusion, and lethargy. Raised C reactive protein was seen in a higher proportion of newborns with Candida (60%) sepsis and E. coli (50%) sepsis. Severe thrombocytopenia was seen in 53%–62% newborns with gram-negative and fungal sepsis. Metabolic acidosis was seen in all gram-negative sepsis neonates, particularly in &gt;80% cases of Klebsiella and Candida sepsis. Mortality was highest and statistically significant in KP (55.4%) and Citrobacter koseri (55.6%) sepsis ( p = .004). The statistically significant risk factors for mortality included neonates with raised C Reactive Protein (CRP). Most of the gram-negative pathogens were sensitive to colistin and aminoglycosides and resistant to carbapenems. Conclusion: Observing the initial clinical features at suspicion of sepsis may help predicting the likely pathogen awaiting the final blood/CSF culture report and knowing the antibiotic sensitivity profile of commonly isolated organisms in our NICU helps in the selection of a rational empirical antibiotic.

A retrospective study on the outcome of sepsis among neonates admitted to the neonatal intensive care unit at a tertiary care hospital in Western India

Background: In underdeveloped nations, sepsis is one of the main causes of newborn death. A timely detection of this can reduce the burden of neonatal mortality as well as morbidity. Objective: The aim of this study was to evaluate the prognosis of sepsis at a tertiary care facility in Western India to identify risk factors and increase infant survival rates. Materials and Methods: A retrospective study was conducted on neonates admitted between November 16, 2021, and November 15, 2022 (for 1 year duration), at the neonatal intensive care unit (NICU) of GMERS Medical College, Gandhinagar. A dataset was created consisting of neonates with the final diagnosis of sepsis, and the outcome was analyzed based on various parameters. Results: Out of 1309 NICU admissions, 130 (9.93%) were sepsis cases. Out of 130 sepsis cases, 72 (55.38%) were male and 58 (44.62%) were female, 62 (47.69%) were inborn and 68 (52.31%) were outborn, and 26 (20%) cases were low birth weight (LBW), 18 (13.84%) were very LBW, 12 (9.23%) were extreme LBW, and 74 (56.92%) were normal birth weight neonates. Out of 130 sepsis cases, 84 (64.61%) cases were preterm, and 46 (35.39%) cases were full-term. In 105 cases, out of 130 total sepsis patients, pathogens were isolated. The most common organism was Staphylococcus (62 cases/59.04%). Conclusion: According to this study, the likelihood of developing sepsis was inversely associated with birth weight. A high percentage of neonatal sepsis cases (9.93%) were found, where 96 (73.84%) neonates were successfully discharged. This study is helpful to identify multiple risk factors such as preterm (64.61%), male gender (55.35%), and outborn (52.31%). Antibiotic susceptibility pattern reveals that more number of resistance cases will be coming, posing a serious threat of neonatal sepsis morbidity.

Gemcitabine-based conditioning compared to BEAM/BEAC conditioning prior to autologous stem cell transplantation for non-Hodgkin lymphoma: No difference in outcomes.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.

Hirurško lečenje komplikovane hidatidoze ductus choledochus-a tokom pandemije COVID-19 - efikasnost i ograničenja radiološke službe i hirurgije u vanrednim uslovima

Introduction: While uncomplicated echi-nococcal cysts can grow in the liver for years without symptoms, complicated hydatid cysts (CHC) present distinct clinical characteristics that necessitate urgent treatment. Case Report: We present a case of acute biliary obstruction, cholangitis, and sepsis due to massive cho-ledocho-hydatididosis in an 84-year-old COVID-positive patient during the COVID-19 pandemic. Imaging revealed a multicystic lesion in liver segments V and VIII that compressed surrounding liver tissue, leading to intrahepatic duct dilation. A daughter cyst in the ductus choledochus was confirmed during surgery. An attempt at endoscopic retrograde cholangiopancrea-tography (ERCP) was unsuccessful. We performed an open pericystectomy with total cystectomy and choled-ochotomy, carefully evacuating all hydatid cysts. The postoperative course was uneventful, and the patient was discharged without surgical complications. Conclusion: Complicated hydatid cysts (CHC) leading to acute biliary obstruction require prompt diagnosis and indicate the need for rapid evacuation of the cyst and correction of complications.