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1.
Article in English | MEDLINE | ID: mdl-38957958

ABSTRACT

Introduction: Necrotizing fasciitis (NF) and sepsis shock (SS) are both severe and life-threatening conditions requiring specialized care, including palliative care (PC), to optimize comfort. However, data on the utilization of PC in this population, including racial and gender differences, are limited. Methods: We used the National Inpatient Sample (NIS) database from 2016 to 2020 to extract data on patients with NF and SS as well as PC utilization. Chi-squared tests and multivariate linear regression models were utilized to analyze relationships between categorical and continuous variables, respectively. Multivariable logistic regression was used to determine adjusted odds ratios (aORs) and 95% confidence intervals (CI) for various outcomes among various gender and racial groups. Mann-Kendall trend test was used to assess mortality trends over time. Results: Among the 11,260 patients with NF and SS, 2,645 received PC whereas 8,615 did not. Female patients had significantly higher odds of receiving PC versus males (aOR: 1.42, 95% CI 1.27-1.58). No significant racial differences in PC utilization were observed. Patients receiving PC had higher odds of in-hospital mortality (aOR: 1.18, 95% CI 1.03-1.35). No significant trend in in-hospital deaths was observed over the study period. PC was associated with significantly shorter length-of-stay and lower costs. Conclusion: Our study provides comprehensive insights, and identifies gender differences in PC utilization in NF and SS patients. Further research must aim to refine delivery strategies and address potential differences in PC.

2.
Crit Care ; 28(1): 216, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961499

ABSTRACT

BACKGROUND: Norepinephrine (NE) is a cornerstone drug in the management of septic shock, with its dose being used clinically as a marker of disease severity and as mortality predictor. However, variations in NE dose reporting either as salt formulations or base molecule may lead to misinterpretation of mortality risks and hinder the process of care. METHODS: We conducted a retrospective analysis of the MIMIC-IV database to assess the impact of NE dose reporting heterogeneity on mortality prediction in a cohort of septic shock patients. NE doses were converted from the base molecule to equivalent salt doses, and their ability to predict 28-day mortality at common severity dose cut-offs was compared. RESULTS: 4086 eligible patients with septic shock were identified, with a median age of 68 [57-78] years, an admission SOFA score of 7 [6-10], and lactate at diagnosis of 3.2 [2.4-5.1] mmol/L. Median peak NE dose at day 1 was 0.24 [0.12-0.42] µg/kg/min, with a 28-day mortality of 39.3%. The NE dose showed significant heterogeneity in mortality prediction depending on which formulation was reported, with doses reported as bitartrate and tartrate presenting 65 (95% CI 79-43)% and 67 (95% CI 80-47)% lower ORs than base molecule, respectively. This divergence in prediction widened at increasing NE doses. When using a 1 µg/kg/min threshold, predicted mortality was 54 (95% CI 52-56)% and 83 (95% CI 80-87)% for tartrate formulation and base molecule, respectively. CONCLUSIONS: Heterogeneous reporting of NE doses significantly affects mortality prediction in septic shock. Standardizing NE dose reporting as base molecule could enhance risk stratification and improve processes of care. These findings underscore the importance of consistent NE dose reporting practices in critical care settings.


Subject(s)
Norepinephrine , Shock, Septic , Humans , Shock, Septic/drug therapy , Shock, Septic/mortality , Aged , Female , Male , Retrospective Studies , Middle Aged , Norepinephrine/therapeutic use , Norepinephrine/administration & dosage , Vasoconstrictor Agents/therapeutic use , Vasoconstrictor Agents/administration & dosage , Cohort Studies
3.
JAMIA Open ; 7(3): ooae066, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38966078

ABSTRACT

Objectives: The publication of the Phoenix criteria for pediatric sepsis and septic shock initiates a new era in clinical care and research of pediatric sepsis. Tools to consistently and accurately apply the Phoenix criteria to electronic health records (EHRs) is one part of building a robust and internally consistent body of research across multiple research groups and datasets. Materials and Methods: We developed the phoenix R package and Python module to provide researchers with intuitive and simple functions to apply the Phoenix criteria to EHR data. Results: The phoenix R package and Python module enable researchers to apply the Phoenix criteria to EHR datasets and derive the relevant indicators, total scores, and sub-scores. Discussion: The transition to the Phoenix criteria marks a major change in the conceptual definition of pediatric sepsis. Applicable across differentially resourced settings, the Phoenix criteria should help improve clinical care and research. Conclusion: The phoenix R package and Python model are freely available on CRAN, PyPi, and GitHub. These tools enable the consistent and accurate application of the Phoenix criteria to EHR datasets.

4.
Front Immunol ; 15: 1352789, 2024.
Article in English | MEDLINE | ID: mdl-38966639

ABSTRACT

Introduction: Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Methods: Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. Results: The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. Discussion: The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.


Subject(s)
Pneumonia , Polymorphism, Single Nucleotide , Receptors, Purinergic P2X7 , Sepsis , Shock, Septic , Humans , Receptors, Purinergic P2X7/genetics , Male , Female , Shock, Septic/genetics , Shock, Septic/mortality , Shock, Septic/immunology , Middle Aged , Pneumonia/genetics , Pneumonia/mortality , Aged , Sepsis/genetics , Sepsis/mortality , Genetic Predisposition to Disease , Adenosine Triphosphate/metabolism , Adult , Aged, 80 and over
5.
Heliyon ; 10(11): e32454, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38961944

ABSTRACT

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

6.
J Pediatr (Rio J) ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38968957

ABSTRACT

OBJECTIVE: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. METHODS: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. RESULTS: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. CONCLUSION: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital.

7.
Chest ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972348

ABSTRACT

BACKGROUND: Vasopressor administration at an appropriate time is crucial but the optimal timing remains controversial. RESEARCH QUESTION: Does early versus late norepinephrine (NE) administration impact the prognosis of septic shock? STUDY DESIGN AND METHODS: Searches were conducted on PubMed, EMBASE, the Cochrane Library, and KMBASE. We included studies of adults with sepsis and categorized patients into early and late NE group according to specific time points or differences in norepinephrine use protocols. The primary outcome was overall mortality. The secondary outcomes included length of stay in the intensive care unit, days free from ventilator use, days free from renal replacement therapy, days free from vasopressor use, adverse events, and total fluid volume. RESULTS: Twelve studies (4 randomized controlled trials [RCTs], 8 observational) comprising 7,281 patients were analyzed. For overall mortality, no significant difference was found between the early NE group and late NE group in RCTs (odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.19) or observational studies (OR, 0.83; 95% CI, 0.54-1.29). In the two RCTs without a restrictive fluid strategy that prioritized vasopressors and lower intravenous fluid volumes, the early NE group showed significantly lower mortality than the late NE group (OR 0.49, 95%, CI, 0.25-0.96). The early NE group demonstrated more mechanical ventilator-free days in observational studies (MD, 4.06; 95% CI, 2.82-5.30). The incidence of pulmonary edema was lower in the early NE group in the three RCTs that reported this outcome (OR 0.43; 95% CI, 0.25-0.74). No differences were found in the other secondary outcomes. INTERPRETATION: Overall mortality did not differ significantly between early and late NE administration for septic shock. However, early NE administration appeared to reduce pulmonary edema incidence, and mortality improvement was observed in studies without fluid restriction interventions, favoring early NE use.

9.
Heliyon ; 10(11): e32407, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38947441

ABSTRACT

Background: Colchicine is a common therapeutic agent for inflammatory conditions such as gout, yet its narrow therapeutic range frequently results in cases of overdose and subsequent poisoning. Acute colchicine poisoning can be difficult to identify due to its nonspecific clinical manifestations, posing a diagnostic challenge for emergency physicians without a clear history of colchicine ingestion. Case presentation: This report describes a tragic case of acute colchicine poisoning that resulted in three familial homicides. The patients presented with fever, abdominal pain, and diarrhea, which rapidly escalated to shock during their emergency department visits. Laboratory tests revealed a marked leukocytosis, mild elevation in procalcitonin (PCT), significantly elevated creatine kinase (CK) and CK-MB levels, and liver function abnormalities. Despite treatment with carbapenem antibiotics and aggressive fluid resuscitation, the patients' condition deteriorated, marked by a progressive decline in leukocytes and neutrophils. Initially misdiagnosed as septic shock, the ineffectiveness of the standard treatment protocols led to a fatal outcome for all three individuals. Conclusion: Emergency physicians should consider acute colchicine poisoning as a differential diagnosis in patients presenting with shock and the following clinical indicators: (1) pronounced increase in peripheral leukocytes with a disproportionate rise in neutrophils; (2) discordance between the level of serum procalcitonin and the severity of presumed septic shock; (3) early increase in serum creatine kinase (CK) and CK-MB; (4) poor response to antibiotics and resuscitative efforts, accompanied by a continuous decrease in white blood cells and neutrophils. This case underscores the critical need for awareness of colchicine toxicity in the emergency setting, particularly when the clinical presentation mimics septic shock but fails to respond to standard treatments.

10.
Arch. argent. pediatr ; 122(3): e202310123, jun. 2024. ilus
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1554997

ABSTRACT

Las duplicaciones del tracto alimentario son un conjunto heterogéneo de anomalías congénitas del tubo digestivo. Su forma de presentación es variada, y pueden desarrollar distintas complicaciones libradas a su evolución natural. La infección es una complicación poco frecuente, pero que no puede desconocerse por la gravedad que implica. Se presenta el caso de una paciente de 2 años de edad, previamente sana, con una complicación atípica de una duplicación del tracto alimentario: un shock séptico. Consultó inicialmente por distensión y dolor abdominal asociado a una masa abdominal palpable. Los estudios imagenológicos evidenciaron una formación líquida parcialmente tabicada en el hemiabdomen derecho. Durante la internación, se presentó una infección intratumoral, que evolucionó al shock séptico. Respondió favorablemente al tratamiento médico del shock, y se realizó la exéresis quirúrgica posteriormente. La anatomía patológica confirmó la duplicación del tracto alimentario.


Alimentary tract duplications are heterogenous congenital anomalies of the digestive tract. Their form of presentation is varied, and they may lead to different complications, depending on their natural course. Infection is a rare complication, but it cannot be ignored because of its severity. Here we describe the case of an otherwise healthy 2-year-old girl with an atypical complication of alimentary tract duplication: septic shock. She initially consulted due to abdominal distension and pain associated with a palpable abdominal mass. The imaging studies showed a partial fluid septation in the right side of the abdomen. During hospitalization, an intratumoral infection developed, which progressed to septic shock. The patient responded favorably to medical treatment for shock, and surgical resection was subsequently performed. The pathology report confirmed the presence of alimentary tract duplication.


Subject(s)
Humans , Female , Child, Preschool , Shock, Septic/etiology , Digestive System Abnormalities/surgery , Digestive System Abnormalities/complications , Digestive System Abnormalities/diagnosis , Pain , Gastrointestinal Tract , Ileum
11.
Clin Exp Med ; 24(1): 137, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937383

ABSTRACT

Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy. Patient characteristics, sepsis criteria [Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome (SIRS)], microbiology results, and associations with progression-free survival (PFS) were analyzed. In this cohort of 92 critically-ill patients, pathogenic organisms were identified via microbiological culture in 74 cases. However, among the remaining 18 culture-negative patients, 9 exhibited a SIRS score of 2 and another 9 had a SIRS score of 4, suggestive of a clinical presentation consistent with sepsis despite negative cultures. Common comorbidities included renal failure (60%), anemia (71%), and bone disease (83%). Gram-negative (28%) and Gram-positive (23%) bacteria were frequent causative organisms, along with fungi (20%). Cox Univariate analyses for PFS showed statically significant HR in patients with albumin ≥ 3.5 vs < 3.5 (HR = 5.04, p < 0.001), Karnofsky performance status ≥ 80 vs < 80 (HR = 2.01, p = 0.002), and early-stage vs late-stage disease by International Staging System (HR = 4.76 and HR = 12.52, both p < 0.001) and Revised International Staging System (R-ISS III vs R-ISS I, HR = 7.38, p < 0.001). Sepsis is common in NDMM and associated with poor outcomes. Risk stratification incorporating sepsis severity, comorbidities, and disease stage may help guide preventive strategies and optimize MM management.


Subject(s)
Multiple Myeloma , Sepsis , Humans , Multiple Myeloma/complications , Multiple Myeloma/microbiology , Retrospective Studies , Male , Female , Aged , Middle Aged , Sepsis/microbiology , Italy/epidemiology , Aged, 80 and over , Adult , Tertiary Care Centers
12.
Sci Rep ; 14(1): 14887, 2024 06 27.
Article in English | MEDLINE | ID: mdl-38937631

ABSTRACT

The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock.


Subject(s)
Norepinephrine , Shock, Septic , Humans , Shock, Septic/mortality , Shock, Septic/blood , Infant, Newborn , Norepinephrine/administration & dosage , Male , Female , Retrospective Studies , ROC Curve , Apgar Score
13.
Proc Natl Acad Sci U S A ; 121(26): e2319322121, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38900789

ABSTRACT

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.


Subject(s)
COVID-19 , Receptor for Advanced Glycation End Products , SARS-CoV-2 , Humans , Receptor for Advanced Glycation End Products/metabolism , COVID-19/immunology , COVID-19/metabolism , COVID-19/pathology , COVID-19/complications , COVID-19/virology , Animals , Mice , Inflammation/metabolism , Inflammation/pathology , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology , Respiratory Distress Syndrome/virology , Lung Injury/immunology , Lung Injury/metabolism , Lung Injury/pathology , High Mobility Group Proteins/metabolism , High Mobility Group Proteins/genetics , Male , Lung/pathology , Lung/metabolism , Lung/immunology , Female
14.
Thromb Res ; 241: 109072, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38945093

ABSTRACT

INTRODUCTION: Dysregulated host response to infection causes life-threatening organ dysfunction. Excessive inflammation and abnormal blood coagulation can lead to disseminated intravascular coagulation (DIC) and multiple-organ failure in the late sepsis stages. Platelet function impairment in sepsis contributes to bleeding, secondary infection, and tissue injury. Platelet transfusion is considered in patients with sepsis with DIC and bleeding; however, its benefits are limited and of low quality. Fibrinogen plays a crucial role in platelet function, and establishing a fibrin network binds to activated integrin αIIbß3 and promotes outside-in signaling that amplifies platelet functions. However, the role of fibrinogen in sepsis-induced platelet dysfunction remains unclear. MATERIALS AND METHODS: We evaluated the effects of fibrinogen on platelet hyporeactivity during septic shock in adult male Wistar rats using lipopolysaccharide (LPS) injection and cecal ligation and puncture (CLP) surgery. Changes in the hemodynamic, biochemical, and coagulation parameters were examined. Platelet activation and aggregation were measured using whole-blood assay, 96-well plate-based aggregometry, and light-transmission aggregometry. Additionally, platelet adhesion, spreading, and fibrin clot retraction were evaluated. RESULTS: Rats with LPS- and CLP-induced sepsis displayed considerable decreases in plasma fibrinogen levels and platelet aggregation, adhesion, spreading, and clot retraction. The aggregation of platelets obtained from rats with sepsis was markedly augmented by fibrinogen supplementation. Additionally, fibrinogen administration improved platelet adhesion, spreading, and clot retraction in rats with sepsis. CONCLUSIONS: Fibrinogen supplementation could serve as a potential therapeutic intervention for alleviating platelet hyporeactivity in patients with sepsis and bleeding.

15.
Clin Liver Dis ; 28(3): 525-539, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945641

ABSTRACT

Patients with cirrhosis and clinically significant portal hypertension are at high risk of developing bacterial infections (BIs) that are the most common trigger of acute decompensation and acute-on-chronic liver failure. Furthermore, after decompensation, the risk of developing BIs further increases in an ominous vicious circle. BIs may be subtle, and they should be ruled out in all patients at admission and in case of deterioration. Timely administration of adequate empirical antibiotics is the cornerstone of treatment. Herein, we reviewed current evidences about pathogenesis, clinical implications and management of BIs in patients with cirrhosis and portal hypertension.


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Hypertension, Portal , Liver Cirrhosis , Humans , Hypertension, Portal/etiology , Hypertension, Portal/complications , Liver Cirrhosis/complications , Bacterial Infections/complications , Bacterial Infections/drug therapy , Anti-Bacterial Agents/therapeutic use , Acute-On-Chronic Liver Failure/etiology , Acute-On-Chronic Liver Failure/therapy
16.
Sci Rep ; 14(1): 14468, 2024 06 24.
Article in English | MEDLINE | ID: mdl-38914630

ABSTRACT

Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.


Subject(s)
Lipoproteins , Shock, Septic , Thromboplastin , Humans , Shock, Septic/blood , Shock, Septic/metabolism , Thromboplastin/metabolism , Male , Female , Lipoproteins/blood , Lipoproteins/metabolism , Middle Aged , Aged , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Disseminated Intravascular Coagulation/blood , Case-Control Studies , Adult , Biomarkers/blood
17.
J Spec Oper Med ; 24(2): 94-102, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38865657

ABSTRACT

During distributed maritime operations, individual components of the naval force are more geographically dispersed. As the U.S. Navy further develops this concept, smaller vessels may be operating at a significant time and distance away from more advanced medical capabilities. Therefore, during both current and future contested Distributed Maritime Operations, Role 1 maritime caregivers such as Independent Duty Corpsman will have to manage patients for prolonged periods of time. This manuscript presents an innovative approach to teaching complex operational medicine concepts (including Prolonged Casualty Care [PCC]) to austere Role 1 maritime caregivers using a hypothetical scenario involving a patient with sepsis and septic shock. The scenario incorporates the Joint Trauma System PCC Clinical Practice Guidelines (CPG) and other standard references. The scenario includes a stem clinical vignette, expected clinical changes for the affected patient at specific time points (e.g., time 0, 1, 2, and 48h), and expected interventions based on the PCC CPG and available shipboard equipment. Epidemiology of sepsis in the deployed environment is also reviewed. This process also identifies opportunities to improve training, clinical skills sustainment, and standard shipboard medical supplies.


Subject(s)
Naval Medicine , Sepsis , Humans , Sepsis/therapy , Ships , Military Personnel/education , Shock, Septic/therapy , Military Medicine/methods , Time Factors , United States
18.
Clin Case Rep ; 12(7): e9095, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38911922

ABSTRACT

Key Clinical Message: Leptospirosis is an important zoonosis worldwide. Due to nonspecific clinical manifestation and poor recognition in non-epidemic area, there is often a delay in diagnosis and treatment. Early diagnosis from Metagenomic next-generation sequencing test is crucial for timely intervention. Abstract: We presented a case of a 19-year-old male patient who developed leptospirosis infection characterized by acalculous cholecystitis and septic shock after typhoon events. Metagenomic next-generation sequencing (mNGS) helped to early diagnose leptospirosis infection. Finally, the patient achieved full recovery following the antibiotic treatment in addition to supportive care and was discharged.

19.
Eur J Pediatr ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38916738

ABSTRACT

This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups. CONCLUSIONS: The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children.Prospero registration: CRD42020209066. WHAT IS KNOWN: • Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children. WHAT IS NEW: • BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia.

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