Critical Care Medicine最新文献

Objectives: Sepsis triggers both excessive inflammation and immunosuppression, the latter partly characterized by CD4+ T-cell depletion. The mechanisms underlying this depletion, especially its interplay with cytokine storms driven by inflammatory factors such as interleukin (IL)-6, remain unclear. This study aimed to elucidate the molecular mechanisms contributing to CD4+ T-cell depletion in sepsis, focusing specifically on the IL-6/Janus kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3) signaling axis and programmed cell death.

Design: Prospective cohort study.

Setting: Adult ICUs at a university hospital.

Patients: Adult sepsis and septic shock patients without any documented immune comorbidity.

Interventions: None.

Measurements and main results: A prospective analysis enrolled 151 patients (93 sepsis, 58 septic shock) and 20 controls. Flow cytometry and enzyme-linked immunosorbent assay were used to assess immune cell populations and cytokine profiles, with multivariate analyses exploring their interrelationships. An additional 30 sepsis patients and ten controls were recruited to investigate mechanisms. Peripheral blood mononuclear cells (PBMCs) underwent RNA sequencing (RNA-seq). Isolated CD4+ T cells were stimulated with IL-6 in vitro, followed by treatment with specific inhibitors targeting pyroptosis, apoptosis, necroptosis, the JAKs/STAT3 pathway, or receptor-interacting protein kinase 1 (RIPK1). Western blotting, flow cytometry, immunofluorescence, Cell Counting Kit-8 assays, and interferon-gamma staining evaluated cell death pathways, PANoptosome (a complex mediating apoptosis, pyroptosis and necroptosis)-assembly, and function. Significant CD4+ T-cell loss occurred in both sepsis and septic shock groups, strongly correlating with elevated IL-6 levels. Sepsis PBMC RNA-seq revealed activated IL-6/JAKs/STAT3 signaling and upregulated apoptosis/pyroptosis/necroptosis genes. In vitro, IL-6 induced pyroptosis, apoptosis, and necroptosis (PANoptosis) in CD4+ T cells via IL-6/JAKs/STAT3-dependent RIPK1-PANoptosome assembly. Inhibiting JAKs/STAT3 or RIPK1 significantly reduced PANoptosis, partially restored CD4+ T-cell viability and functional capacity.

Conclusions: PANoptosis has been observed to be a form of CD4+ T-cell death in sepsis patients. Evidence suggests that IL-6 may be associated with the exhaustion process, mechanistically involving the activation of the JAKs/STAT3 pathway. It is also hypothesized that this process might be linked to RIPK1-PANoptosome-mediated PANoptosis.

Objectives: To evaluate the diagnostic performance of a rapid point-of-care immunoassay measuring pancreatic stone protein (PSP) for early sepsis identification within the first three days of ICU admission. Subgroup analyses (sex, age, febrile status) were conducted, and the combined diagnostic value of PSP and C-reactive protein (CRP) was assessed.

Design: Multicenter, prospective, observational study.

Patient: Four hundred sixty-six adults the ICU.

Setting: Six ICUs in the United States who were expected to required at least 24 hours of ICU care.

Interventions: None.

Measurements and main results: We calculated the Youden Index to evaluate the clinical performance of the PSP assay, and the resulting threshold was used to identify patients with sepsis. Diagnostic performance metrics included sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-). Receiver operating characteristic analysis were performed for PSP and CRP. At the optimal PSP cutoff point of 117 ng/mL, PSP demonstrated a sensitivity of 74.2%, specificity of 67.8%, accuracy of 71.0%, PPV of 70.3%, NPV of 71.9%, and LR+ and LR- ratios of 2.30 and 0.38, respectively. Combining PSP and CRP improved diagnostic specificity to 95.2%. Subgroup analyses demonstrated consistent performance across sex, and higher specificity was observed in patients 18-60 years old. In febrile patients, PSP achieved high specificity (87.5%) but lower sensitivity (63.6%). In non-febrile patients, sensitivity and specificity were 67.7% and 76.6%, respectively.

Conclusions: PSP can serve as a biomarker for the early identification of sepsis. Diagnostic performance across diverse ages, sex, and clinical presentation supports the assay's broad applicability. The combination of PSP and CRP enhances diagnostic specificity for sepsis detection, offering a complementary approach to improve sepsis detection and lead to earlier appropriate management.

Objectives: While potential risks for limb ischemia have been explored in studies of venoarterial extracorporeal membrane oxygenation (ECMO), they remain inadequately defined for patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). We identified risk factors for the development of lower limb ischemia during ECPR using a large nationwide ECPR cohort.

Design: A post hoc analysis was conducted using a nationwide, multicenter, retrospective study (Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan II [SAVE-J II]).

Setting: Thirty-six institutions from 2013 to 2018.

Patients: Adult patients who underwent ECPR for out-of-hospital cardiac arrest.

Interventions: None.

Measurements and main results: Lower limb ischemia was defined as the requirement for a therapeutic distal perfusion catheter (DPC), fasciotomy, or amputation. Risk factors for lower limb ischemia were assessed using multivariate logistic regression models that included patient characteristics, ECPR-related information, and resuscitation content as potential confounders. Of the 969 patients, 72 (7.4%) developed lower limb ischemia. No significant differences were observed regarding background characteristics, cannulation location, puncture method, or venoarterial ECMO catheter size between patients with and without limb ischemia. However, a prophylactic DPC was less frequently employed in patients with lower limb ischemia than in those without (4 [5.6%] vs. 219 [24.4%]; p < 0.001). Higher incidences of cannulation-related bleeding and cannula malposition were observed in patients with limb ischemia than in those in patients without limb ischemia (22 [30.6%] vs. 162 [18.1%]; p = 0.009 and 9 [12.5%] vs. 29 [3.2%]; p < 0.001, respectively). Multivariable analyses revealed that prophylactic DPC placement was associated with a lower risk of limb ischemia (0.20 [0.07-0.55]; p = 0.002), whereas cannulation-related bleeding and cannula malposition were linked to an increased risk of lower limb ischemia (1.83 [1.06-3.14]; p = 0.030 and 3.81 [1.68-8.64]; p = 0.001, respectively).

Conclusions: Lower limb ischemia during ECPR would be anticipated in patients with cannulation-related complications, and prophylactic DPC placement may be considered to mitigate the risk of lower limb ischemia.

Objectives: To evaluate the feasibility of randomizing children on extracorporeal membrane oxygenation (ECMO) to one of two prophylactic platelet transfusion thresholds.

Design: Randomized controlled trial.

Setting: Ten ECMO centers (nine in United States, one in Israel).

Patients: Critically ill children (0 to younger than 18 yr), supported on ECMO, with no or minimal bleeding within 24 hours of cannulation.

Interventions: Children were randomized to a higher platelet threshold (transfused when platelet count < 90 × 10 9 /L) or a lower platelet threshold (transfused when platelet count < 50 × 10 9 /L). Primary feasibility outcome was pre-transfusion platelet count to test for a difference between strategies. Primary safety outcome was progression to severe bleeding, severe clotting, and/or all-cause mortality.

Measurements and main results: Of 159 patients screened for eligibility, 77% (123/159) met eligibility criteria. Sixty-five percent (80/123) of caregivers were approached for consent. Consent was obtained in 63% (50/80). Enrolled children had a median age of 0.2 years (interquartile range 0.0; 1.7) and 88% (44/50) were supported by veno-arterial (V-A) ECMO. The model-adjusted mean difference in pre-transfusion platelet count between the groups was 32 × 10 9 /L ( p < 0.001). Compliance with assigned transfusion threshold was 99.2%. Eleven (22%) children experienced the primary safety outcome. Progression to severe bleeding occurred in 14% (7/50) of patients, whereas progression to severe clotting was observed in 4% (2/50).

Conclusions: Non-bleeding children on ECMO can be screened, enrolled and randomized to different platelet transfusion strategies within 24 hours of cannulation. Compliance with the protocol was excellent with significant separation in pre-transfusion platelet counts between the arms. Severe bleeding and severe clotting occurred at similar rates in both thresholds. A larger, definitive trial is feasible and needed.

Objectives: To review the systems of care, logistics, staffing considerations, and best practices to facilitate safe interhospital transfer of critically ill patients with cardiac pathology.

Data sources: Publications were identified using a Medline search using terms related to interhospital transfer, systems of care, published guidelines, and cardiac conditions.

Study selection: A screening and shortlisting process was carried out by three of the authors to identify relevant studies, case reports, and guidelines.

Data extraction: Data from relevant articles were qualitatively evaluated.

Data synthesis: The interhospital transfer of critically ill cardiac patients presents significant clinical and logistical challenges. These patients benefit from access to specialized care but require meticulous physiologic management during transport and are at risk of deterioration. Structured communication systems, telemedicine, and specialized critical care transfer teams enhance patient selection, pre-transfer optimization, and in-transit management. The use of mechanical circulatory support devices, such as intra-aortic balloon pumps and microaxial flow pumps, adds further complexity.

Conclusions: Despite the high-acuity nature of these transfers, evidence from case series and observational studies demonstrates that, with appropriately trained teams and rigorous protocols, critically ill cardiac patients can be safely transported between facilities. This review highlights the importance of structured protocols, telemedicine, and specialized transport teams.

Objectives: The evidence supporting the use of noninvasive positive pressure ventilation (NPPV) during severe asthma exacerbations is limited. We determined the annual trend in NPPV use, endotracheal intubations, and in-hospital mortality among all hospitalizations for an asthma exacerbation. We additionally evaluated the association between NPPV use and subsequent endotracheal intubation and in-hospital mortality.

Design: Retrospective, propensity-score-matched cohort study.

Setting: Administrative data from Healthcare Cost and Utilization Project's State Inpatient Databases for New York and Florida, 2006-2019.

Patients: Patients 5-80 years old hospitalized with an asthma exacerbation.

Interventions: Receipt of NPPV.

Measurements and main results: Among 296,788 hospitalizations for an asthma exacerbation between 2006 and 2018, NPPV use for an asthma exacerbation increased from 1.2% to 7.4% (absolute difference, 6.1%; 95% CI, 5.6-6.7%) in adults and from 0.7% to 7.1% (absolute difference, 6.4%; 95% CI, 5.5-7.3%) in pediatric patients. Among 41,902 ICU encounters, we propensity-score matched 1,972 adult and 1,622 pediatric patients who received NPPV with 6,510 adults and 4,766 pediatric patients who did not receive NPPV. NPPV use was associated with a decreased risk of subsequent intubation (risk ratio [RR], 0.48; 95% CI, 0.40-0.57) and improved in-hospital mortality (RR, 0.33; 95% CI, 0.21-0.54) in adults. In pediatric patients, use of NPPV was associated with a decreased risk of intubation (RR, 0.50; 95% CI, 0.29-0.89), but not significant for an improvement in in-hospital mortality (RR, 0.41; 95% CI, 0.15-1.11).

Conclusions: NPPV use for asthma exacerbations has increased. In adult and pediatric patients, NPPV use for an asthma exacerbation was associated with a decreased risk of endotracheal intubation. Furthermore, NPPV use for an asthma exacerbation was associated with improved in-hospital mortality in adult patients.