Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Objective To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis. Design Multicentre, double blinded, placebo controlled phase 3 trial. Setting 22 centres in China, September 2016 to December 2020. Participants 1106 adults aged 18-85 years with a diagnosis of sepsis according to sepsis-3 criteria and randomly assigned in a 1:1 ratio to receive thymosin α1 (n=552) or placebo (n=554). A stratified block method was used for randomisation, and participants were stratified by age (<60 and ≥60 years) and centre. Interventions Subcutaneous injection of thymosin α1 or placebo every 12 hours for seven days unless discontinued owing to discharge from the intensive care unit, death, or withdrawal of consent. Main outcome measure The primary outcome was 28 day all cause mortality after randomisation. All analyses were based on a modified intention-to-treat set, including participants who received at least one dose of study drug. Results Of 1106 adults with sepsis enrolled in the study, 1089 were included in the modified intention-to-treat analyses (thymosin α1 group n=542, placebo group n=547). 28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test). No secondary or safety outcome differed statistically significantly between the two groups. The prespecified subgroup analysis showed a potential differential effect of thymosin α1 on the primary outcome based on age (<60 years: hazard ratio 1.67, 1.04 to 2.67; ≥60 years: 0.81, 0.61 to 1.09; P for interaction=0.01) and diabetes (diabetes: 0.58, 0.35 to 0.99; no diabetes: 1.16, 0.87 to 1.53; P for interaction=0.04). Conclusions This trial found no clear evidence to suggest that thymosin α1 decreases 28 day all cause mortality in adults with sepsis. Trial registration ClinicalTrials.gov NCT02867267.

Background: Despite advances in understanding sepsis pathophysiology and extensive research, few treatments effectively target its underlying immune dysfunction. Thymosin α1 (Tα1) shows promise as an immunomodulator, but its impact on sepsis remains unclear.Methods: A search strategy was designed to include any prospective clinical studies using Tα1 for assessing 28-day mortality in patients with sepsis, excluding combination therapy studies. We conducted trial sequential analysis (TSA) to assess the robustness of meta-analyses findings. Heterogeneity of treatment effects (HTE) was conducted based on individual data from two multicenter randomized clinical trials (RCTs), with result credibility assessed through the instrument to assess the credibility of effect modification analyses (ICEMAN).Results: Out of 3003 identified studies, 11 RCTs met the inclusion criteria (967 patients in Tα1 group and 960 patients in control group). The comprehensive meta-analysis demonstrated a significant reduction in 28-day mortality associated with Tα1 administration (OR 0.73, 95%CI: 0.59-0.90, P = 0.003). Nonetheless, analyses of high-quality (OR 0.82, 95%CI: 0.65-1.03, P = 0.09) and multi-center (OR 0.86, 95%CI: 0.68-1.08, P = 0.20) subgroups did not reveal a mortality benefit. The HTE analysis of multiple subgroups in two large RCTs (representing 75% of the total patients) showed heterogeneity. Potential benefits were noted in subgroups of cancer (moderate credibility), diabetes (low credibility), and coronary heart disease (low credibility). Furthermore, the trial sequential analysis (TSA) suggests that the current sample size is inadequate.Conclusion: Tα1 has the potential to decrease 28-day mortality rates in patients with sepsis; however, it is crucial to recognize that its efficacy differs among various subgroups. These observations underscore the significance of personalized immunotherapy strategies in forthcoming clinical trials.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024628937.

Background: Skeletal muscle is an important organ strongly associated with prognosis in critically ill patients. 60-day mortality represents a key endpoint for evaluating the transitional phase from ICU survival to functional recovery, yet the association between ultrasound-derive muscle indices at ICU admission and 60-day mortality remains unclear. Methods: This dual-center, prospective observational study was performed from January to December 2024. Four ultrasound indices of muscle quantity [thickness and cross-sectional area of the rectus femoris (RF-TH and RF-CSA), thickness of the vastus intermedius (VI-TH), thickness of the quadriceps femoris (QF-TH)], and one index of quality (tibialis anterior pennation angle, TA-PA) were assessed within 24 h of ICU admission. The primary endpoint was 60-day all-cause mortality. To identify predictive factors, multivariable logistic regression analysis was employed. Additionally, a predictive nomogram model was developed. Results: A total of 247 critically ill adult patients were included, with a median age of 61.0 years (51.0–72.0), including 171 males (69.20%). During 60-day follow-up, 53 patients (21.50%) died. Compared with the survivors, the non-survivors exhibited significantly lower RF-TH (0.54 [0.43–0.70] vs. 0.64 [0.48–0.85]cm; P = 0.022), VI-TH (0.64 [0.47–0.86] vs. 0.77 [0.64–1.04]cm; P = 0.002), QF-TH (1.32 [0.96–1.63] vs. 1.48 [1.24–1.97]cm; P =0.005) and TA-PA (7.08[5.63–8.48] vs. 7.94[6.62–9.32]; P =0.002). Among them, TA-PA was identified as an independent predictor of 60-day mortality (β = −0.216, P = 0.035). TA-PA, in conjunction with APACHE II score and prealbumin level, constructed a predictive nomogram, with a consistency index (C-index) of 0.785 (95%CI: 0.728–0.834). Calibration assessed by Spiegelhalter Z -test showed P > 0.05 indicating adequate calibration for the predicted and observed models. Decision curve analysis (DCA) confirmed that the nomogram prediction model had good clinical benefits. Internal validation demonstrated stable model performance, with a concordance statistic (C-index) of 0.785. Compared to the ROC curve based solely on APACHE II score, the nomogram exhibited significantly higher area under the curve (AUC) (0.785, 95%CI: 0.728–0.834 vs. 0.726, 95%CI: 0.666–0.781, P = 0.023). Conclusions: Lower TA-PA at ICU admission is an independent predictor of 60-day mortality. Incorporating this ultrasound-derived muscle quality index with APACHE II score and prealbumin level may improve early risk stratification in critically ill patients.

Background The performance of muscular ultrasound in diagnosing intensive care unit (ICU)-acquired weakness (ICUAW) is debated. We conducted this systematic review and meta-analysis to assess the diagnostic efficacy of muscular ultrasound in ICUAW. Methods Three researchers independently searched PubMed, Web of Science, Embase, Cochrane library, CNKI, VIP and Wanfang databases for articles published before May 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was employed to evaluate the methodological quality of the studies. A random-effects model was utilized to drive the summary estimates of sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI), and summary receiver operating characteristic (SROC) curve was estimated. Additionally, a Fagan nomogram was constructed to calculate the post-test probabilities. Sources of heterogeneity were explored by subgroup analysis and meta-regression. Results This meta-analysis comprised nine prospective studies involving 485 participants, of whom 207 (42.68%) were diagnosed as ICUAW. Overall, the muscular ultrasound exhibited good performance for diagnosing ICUAW, with the area of SROC curve of 0.84 (95%CI 0.81–0.87), sensitivity of 0.76 (95%CI 0.70–0.82), specificity of 0.79 (95%CI 0.73–0.83), and DOR of 11.61 (95%CI 7.43–18.13). The included studies exhibited heterogeneity. Upon subgroup analysis, rectus femoris exhibited significantly superior discriminatory ability in identifying ICUAW when compared to the non-rectus femoris, with higher specificity (0.84 [95%CI 0.76–0.90] versus 0.71 [95%CI 0.64–0.77], p = 0.04) and SROC (0.89 [95%CI 0.86–0.91] versus 0.76 [95%CI 0.72–0.79], p < 0.01). Moreover, cross-sectional area was more effective than thickness, with higher specificity (0.84 [95%CI 0.77–0.89] versus 0.74 [95%CI 0.68–0.79], p = 0.02) and SROC (0.85 [95%CI 0.82–0.88] versus 0.76 [95%CI 0.72–0.80], p < 0.01). Furthermore, the integrated analysis of these two indicators revealed that the cross-sectional area of rectus femoris was statistically superior to the thickness of rectus femoris, with higher SROC (0.87 [95%CI 0.83–0.89] versus 0.80 [95%CI 0.76–0.83], p < 0.01). Conclusion Muscular ultrasound has potential to be a reliable tool for ICUAW diagnosis. Comparing to alternative indices, the cross-sectional area of the rectus femoris exhibits superior diagnostic efficacy and may be considered as a valuable parameter for clinical application.