SHOCK最新文献

Objective: The causality between CMD and sepsis has remained largely unknown. To elucidate this, we conducted a Mendelian randomization (MR) and population study.

Methods: Firstly, we used univariable and multivariable MR analyses to investigate causal associations between CMD and sepsis-related outcomes. We obtained Genome-wide association study summary from both the MRC Integrative Epidemiology Unit and the FinnGen consortium. Subsequently, a two-step mediation MR analysis was performed to explore mediators. Afterward, we conducted an observational study using the MIMIC-IV database, in which multivariable logistic regression models were utilized to examine the relationship between CMD and sepsis-related outcomes.

Results: In the MR study, type 2 diabetes mellitus (T2DM) (OR = 1.058, 95%CI = 1.017-1.100, p = 0.005), obesity (OR = 1.113, 95%CI = 1.057-1.172, p < 0.001) and heart failure (HF) (OR = 1.178, 95% CI = 1.063-1.305, p = 0.002) were independently causally related to sepsis. Obesity (OR = 1.215, 95% CI = 1.027-1.437, p = 0.023) and HF (OR = 1.494, 95% CI = 1.080-2.065, p = 0.015) also showed independent causal associations with sepsis critical care admission. Mediation MR analysis identified 23 blood metabolites potentially causally linked to sepsis (p < 0.05), yet none mediated the relationship between CMD and sepsis. In the observational study, we found associations between sepsis and several conditions including T2DM, obesity, hypertension, stroke, HF, and hyperlipidemia after adjusting for confounding factors. Moreover, hypertension, stroke, HF, coronary artery disease, and hyperlipidemia were linked to sepsis critical care admission.

Conclusion: This study has, for the first time, revealed indicative evidence of a causal relationship between CMD and sepsis through observational and genetic evidence. Taken together, clinical attention to sepsis may be warranted among patients with CMD.

Background: Contrast-induced nephropathy (CIN) is a serious complication following acute coronary syndrome (ACS), leading to increased morbidity and mortality. Machine learning (ML), combined with parameters such as shock indices, can potentially improve CIN risk prediction by analyzing complex variable interactions and creating accessible, clinically applicable models.

Methods: This retrospective case-control study included 719 ACS patients who underwent percutaneous coronary intervention (PCI). Patients were divided into two groups (CIN and non-CIN), and clinical, procedural, and hemodynamic parameters, including shock indices, were analyzed using machine learning algorithms. A new predictive model, CIN-Predict 5, was developed using the Gradient Boosting Machine (GBM) algorithm, incorporating clinically relevant and statistically significant variables. Correlations between model predictions and secondary outcomes, including in-hospital mortality and hospitalization duration, were evaluated.

Results: Among the variables used in the GBM algorithm, the Modified Shock Index emerged as the most significant predictor, with an importance score of 0.25. The CIN-Predict 5 model achieved an AUC of 0.87, outperforming the Mehran Risk Score (AUC = 0.75) for predicting CIN. The secondary outcomes showed that CIN-Predict 5 correlated significantly with in hospital mortality (r = 0.16, p < 0.001) and hospitalization duration (r = 0.20, p < 0.001).

Conclusions: The GBM-based model we developed, utilizing shock indices and derived through ML, provides a practical tool for early identification of high-risk CIN patients post-ACS, enabling timely preventive strategies and improving clinical decision-making.

Background and hypothesis: Resuscitation strategies incorporating fresh frozen plasma have become the standard of care in the management of traumatic hemorrhagic shock. While plasma resuscitation has been shown to augment the circulation and reduce inflammation within the splanchnic and pulmonary circulation, its global effect on the kidney remains unknown. We hypothesized that plasma would improve intra-renal blood flow and reduce parenchymal inflammation when compared to resuscitation with lactated ringer's.

Methods: Animals were randomized into four groups (n = 8): a) baseline, b) hemorrhagic shock alone, c) lactated ringer's resuscitation, and d) fresh frozen plasma resuscitation. Multiplex immunoassays were used to evaluate cytokine and chemokine signaling within the renal cortex and immunohistochemistry was used to identify leukocyte infiltration. Doppler ultrasonography was used to evaluate changes in blood flow and maximum kidney diameter during hemorrhagic shock and resuscitation.

Results: While no difference in resistive index (surrogate for blood flow) within the renal artery or parenchymal vessels was observed between resuscitation strategies, plasma resulted in increased transverse kidney diameter. Plasma administration promoted cytokine/chemokine signaling, resulting in increased infiltration of leukocytes within the renal cortex when compared to lactated ringer's.

Conclusion: Although the clinical benefits of plasma resuscitation mandate its utilization, our current findings highlight the complexities of plasma resuscitation. While the increase in renal diameter may be related to augmentation of the microcirculation, plasma resuscitation did not enhance macro-circulatory blood flow. Furthermore, plasma resuscitation appears to exacerbate inflammation within the renal cortex after hemorrhage. The downstream physiologic implications of plasma-induced inflammation warrant further exploration.

Background: Age and comorbidity significantly impact the prognosis of septic patients and inform treatment decisions. To provide clinicians with effective tools for identifying high-risk patients, this study assesses the predictive value of the age-adjusted Charlson Comorbidity Index (ACCI) and its simplified version, the quick ACCI (qACCI), for mortality in septic patients.

Methods: This retrospective study included septic patients from four Chinese medical centers. The internal validation cohort comprised patients from Xinhua Hospital, Ruijin Hospital, and Huashan Hospital, while participants from Renji Hospital served as the external validation cohort. Machine learning models identified ACCI's feature importance. Restricted cubic spline regression and subgroup analysis assess the correlation between ACCI and mortality risk. The qACCI, derived from the ACCI components, was also evaluated for predictive reliability.

Results: A total of 3,287 septic patients were included: 2,974 in the internal cohort (mean age 67.96 years; 37.5% male) and 313 in the external cohort (mean age 67.90 years; 48.2% male). Machine learning models identified ACCI as a key predictor of in-hospital mortality. A linear correlation was confirmed between ACCI and risks of in-hospital, 30-day, and ICU mortality. Sensitivity analysis revealed consistent results across subgroups, demonstrating significantly higher mortality risks in the moderate- (HR 2.18, 95% CI 1.77-2.70) and high-ACCI (HR 3.72, 95% CI 2.99-4.65) groups compared to the low-ACCI group (HR 1, Reference). The ACCI achieved an AUC of 0.788 for in-hospital mortality, outperforming the SOFA in gastrointestinal (0.831 vs. 0.794) and central nervous system infections (0.803 vs. 0.739). The qACCI showed moderate predictive performance in both the internal (AUC, 0.734) and external (AUC, 0.758) cohorts.

Conclusions: As composite indicators of age and comorbidity, ACCI and qACCI provide valuable and reliable tools for clinicians to identify high-risk patients early.

Background: Adjunctive vasopressors are added to norepinephrine in one-third of adults with septic shock in the United States. However, effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. We sought to synthesize the direct evidence for adjunctive vasopressor administration in adults with septic shock.

Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to June 7, 2023. We included randomized clinical trials of adults with septic shock comparing adjunctive treatment with a vasopressin analogue, angiotensin II, methylene blue, hydroxocobalamin, or catecholamine analogue to standard care vasopressors. The primary outcome was short-term mortality (at or before 28-30 days or intensive care discharge). Secondary outcomes included kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Random-effects meta-analyses were conducted to derive risk ratios (RRs) and 95% CIs. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation.

Results: Of 6763 records, 17 trials (3813 participants) were included. Compared with standard care, adjunctive vasopressor administration may reduce short-term mortality risk (RR, 0.92 [95% CI, 0.85 to 1.00], low certainty, 17 trials [18 participants]) and likely reduces kidney replacement therapy receipt (RR, 0.92 [95% CI, 0.84 to 1.01], moderate certainty, 8 trials [2408 participants]). Adjunctive vasopressor treatment may increase risk of digital/peripheral ischemia (RR, 2.44 [95% CI, 1.17 to 5.10], low certainty, 9 trials [2981 participants]) and venous thromboembolism (RR, 16.48 [95% CI, 0.96 to 283.17], low certainty, 1 trial [321 participants]). There was some evidence that the pooled estimate for short-term mortality was different (interaction P = 0.13) for trials adjudicated as low risk of bias (RR, 0.95 [95% CI, 0.87 to 1.05]) compared with trials adjudicated as some concerns or high risk of bias (RR, 0.82 [95% CI, 0.69 to 0.97]). The findings were robust to multiple sensitivity and subgroup analyses.

Conclusions: In adults with septic shock, adjunctive vasopressors may lower short-term death risk and likely lower kidney replacement therapy risk, but may increase risk of adverse effects. In the United States, adjunctive vasopressor use prevalence in septic shock is disconnected from the low evidence certainty for a favorable mortality-to-risk profile.

Registration: PROSPERO CRD42023427984.

Background: Veno-arterial extracorporeal membrane oxygenation (VA ECMO) and Impella, a transluminal microaxial ventricular assist device, are well-established in the management of cardiogenic shock. No randomised controlled trials (RCTs) directly compare Impella versus VA ECMO to inform their safety and efficacy in cardiogenic shock.

Purpose: This study aims to conduct a systematic review and meta-analysis of propensity score matched / adjusted studies to compare the clinical outcomes of Impella vs. VA ECMO in cardiogenic shock patients.

Methods: A systematic review was undertaken to identify comparative studies of Impella and VA ECMO in cardiogenic shock, which in the absence of RCTs, was limited to observational trials with propensity matched or adjusted outcomes to account for important confounding factors between populations. In-hospital/30-day survival and bleeding events requiring transfusion were meta-analysed using the random effects method.

Results: Five propensity score matched/adjusted studies comparing short-term survival following treatment with Impella vs. VA ECMO were included. A statistically significant difference in in-hospital/30-day mortality was detected between patients treated with Impella (39.6%) vs. VA ECMO (53.8%) (odds ratio [OR] 95% confidence interval [95% CI]: 0.57 [0.44, 0.74]; p < 0.0001). Impella was associated with significantly fewer bleeding events requiring transfusion compared with VA ECMO (19.9% vs. 28.8%, respectively) (OR = 0.61 [0.46, 0.80]; p = 0.0004).

Conclusion: In the absence of RCTs, this meta-analysis of propensity matched/adjusted observational trials represents the highest level of evidence available to date. Impella was associated with improved short-term survival and decreased bleeding events compared to VA ECMO in patients with cardiogenic shock.

Background: Oxidative stress and inflammation are key factors contributing to the complex pathogenesis of abdominal aortic aneurysm (AAA). Tissue inhibitor of metalloproteinases-4 (TIMP-4) expression is reduced in AAA patients. In this study, we investigated the impact of TIMP-4 on the phenotype alterations induced by angiotensin II (Ang-II) in human vascular smooth muscle cells (VSMCs).

Methods: The expression profiling of TIMP-4 and A-kinase anchoring protein (AKAP1) in AAA samples was analyzed using the GSE7084 and GSE140947 datasets. Levels of TIMP-4 and AKAP1 in Ang-II-exposed VSMCs and AAA tissues and serum samples were detected. RNA immunoprecipitation (RIP) experiment and mRNA stability analysis were used to examine the interaction between AKAP1 and TIMP-4 mRNA. The impact of the AKAP1/TIMP-4 cascade on Ang-II-induced VSMC phenotype alterations was determined by evaluating cell viability, apoptosis, oxidative stress, and inflammation.

Results: TIMP-4 and AKAP1 levels were decreased in Ang-II-exposed VSMCs. Increased TIMP-4 expression protected VSMCs against Ang-II-evoked growth impairment in vitro. Moreover, TIMP-4 upregulation diminished Ang-II-evoked oxidative stress and inflammation in VSMCs. Mechanistically, RNA binding protein (RBP) AKAP1 stabilized TIMP-4 mRNA to elevate TIMP-4 expression. TIMP-4 reduction partially abrogated AKAP1-driven suppression on oxidative stress, inflammation, matrix metalloproteinase (MMP9) expression, and nuclear factor kappa B (NF-κB) pathway activation in Ang-II-exposed VSMCs. Additionally, TIMP-4 and AKAP1 levels were downregulated in AAA patients in their AAA tissues and serum samples. TIMP-4 and AKAP1 had good diagnostic values for AAA with high Area under the ROC curve (AUC).

Conclusion: Our study provides evidence for the role of the AKAP1/TIMP-4/NF-κB pathway in Ang-II-induced VSMC inflammation and oxidative stress.

Background: The literature provides hints of seasonal influences on burn injury occurrence and outcomes in temperate climates. Still, data for geographic regions experiencing significant changes in climate throughout the year is scarce. Especially the influence of seasonal differences in burn incidence and outcomes for older adults (≥60 years old), a particularly vulnerable patient cohort with increased mortality and morbidity compared to adults (18-59 years old), has not been investigated so far. Since burns pose a significant public health concern, we aimed to understand seasonal burn injury admission patterns and outcomes to utilize them for targetable prevention measures and effective resource allocation.

Methods: This retrospective single-center cohort study examined data from adult burn patients (≥18 years) with reported %TBSA (Total Body Surface Area) treated between 2006 and 2020 at a provincial burn center in Ontario, Canada. Patients were stratified based on age group: adults (18-59 years) and older adults (≥60 years) Demographic data, comorbidities, and clinical outcomes were compared.

Results: A total of 2445 eligible patients were enrolled in this study. Most burn injuries occurred in Summer, in which the burn patient population was also significantly younger compared to Winter. Summer admissions showed a greater median %TBSA. In contrast, length of stay per %TBSA (LOS:TBSA) revealed a shorter hospitalization in Summer compared to Winter. However, mortality did not show differences across seasons.

Conclusion: Seasonal variations in the incidence and severity of burn injuries, along with associated fluctuations in LOS:TBSA, exist between age groups. This understanding can assist in tailoring burn prevention programs and aid in anticipating the types of burn injuries that may occur during specific times of the year to enhance patient care strategies.

Background: Proteolyse is one of the causes of loss of lean body mass, and depend of insulin. Proteintyrosine phosphatase 1B (PTP1B) and intestinal permeability (evaluated by zonulin) contribute of insulin metabolism. The objectives were to explore the relationship between PTP1B, Zonulin level and body composition during septic shock in humans.

Material and methods: Prospective study including patients admitted to intensive care unit (ICU) for septic shock. Blood samples were collected on days 1 (D1) and 4 (D4) for study expression of PTPT1b (PCR) and zonulin. Muscle mass was evaluated by Fat-Free Mass (FFM) (by Bioelectrical impedance analysis) and rectum femoris cross-sectional area by ultrasound.

Results: We included 52 patients with a mean IGSII 53 [39-65], and a mortality in ICU of 32%. Between D1 and D4, aera of right quadriceps muscle (ARQ) and average of quadriceps muscles (AAQ) decreased (p = 0.002 and 0.009 respectively). We observed no modification in FFM. Median of PTP1b at D1 was 5.03 [2.36-10.96]. Median of plasmatic zonulin at D1 was 156.6 ng/ml [56.3-277.9]. We did not find any correlation between PTP1b, zonulin expression and muscle composition. The mortality rate was more important in patients with a low average quadriceps thickness (QT) or quadriceps area (QA) (p < 0.01), and tendency for patients who had an elevated zonulin in admission. By contrast, we did not observe significant associations between fat-free mass and PTP1B and mortality at D28.

Conclusion: We observed a trend of correlation between the whole blood PTPN1 gene expression at D1 and D4/D1 TLQ, because this is the only data which has a potential to address the relationship body mass change and proteolysis.Keys words: Body composition, malnutrition, PTB1B, septic shock, Zonulin.