Institut Mérieux (France)

Vaccines based on Outer Membrane Vesicles (OMVs) against Neisseria meningitidis require the quantification and characterization of residual capsular polysaccharides (CapsPS) that are not completely removed during the production process. This task is challenging due to the complexity of the CapsPS composition and the presence of OMVs in the samples. Micellar Electrokinetic Chromatography (MEKC) using a negatively charged polyelectrolyte multilayer coating (SMIL) enabled complete separation of CapsPS and OMV residues in approximately 40min. The use of a 4-layer SMIL coating was crucial for achieving good repeatability of migration times (tm). The method allowed the quantification of CapsPS at concentrations between 80 and 600mgL-1. The average number and weight degrees of polymerization were also determined for each batch of OMVs, with polydispersity indexes between 1.2 and 1.5 and degrees of polymerization (DPn) between 30 and 70. This method can be readily implemented in the pharmaceutical industry for the monitoring and documentation of process development.

Cirrhosis progresses through distinct stages, with increasing severity and susceptibility to infections due to cirrhosis-associated immune dysfunction. Lymphocyte-based functional assays are considered the gold standard for assessing immune function, although none have been evaluated across different cirrhosis stages. We conducted a pilot study to assess whether performing interferon-γ (IFN-γ) release assays (IGRA), in response to a nonantigenic mitogen (phytohemagglutinin [PHA]), could help classify immune function and disease severity in 70 patients with cirrhosis awaiting liver transplantation. Disease severity ranged from chronic cirrhosis to acute-on-chronic liver failure. We measured IFN-γ release in response to PHA using a fresh heparinized whole-blood protocol. Progressive reduction in IFN-γ release correlated with increased disease severity parameters (with respect to total bilirubin level and number of organ failure instances). A moderate but highly significant correlation was observed between IFN-γ release and CD8+ T lymphocyte count (r=0.52, P <0.001). As a non-antigen-dependent mitogen, PHA enables the global assessment of lymphocyte IFN-γ-releasing capacity. Our whole-blood results suggest that PHA-IGRA testing may provide a useful parameter for characterizing immune dysfunction in patients with cirrhosis. These findings require further validation in larger cohorts to better define the clinical applicability of PHA-IGRA testing.

BackgroundEarly identification of septic patients who will require vasopressor support could provide a critical window for hemodynamic optimisation, yet current bedside cues often appear only when shock is imminent.ObjectiveWe aimed to develop and validate an interpretable electronic health record (EHR)–based machine-learning model that predicts vasopressor initiation several hours before therapy in intensive care unit (ICU) patients with sepsis.MethodsWe conducted a retrospective study using the MIMIC-IV v2.2 database (2008–2019). We screened adult Sepsis-3 ICU stays and labeled the patients who commenced continuous vasopressor infusions 6 to 48 hours after admission as cases; we defined controls as sepsis patients with ICU stays ≥48 hours and no vasopressor exposure. We performed one to one nearest neighbour matching on age, sex, Charlson index, SOFA score with the cardiovascular component removed, weight, and early lactate/hematocrit availability to minimise confounding. We engineered demographic, physiological, and laboratory features measured from −6 to −2 hours relative to vasopressor initiation (or a matched time point) under multiple parameter combinations. We trained seven algorithms with Monte Carlo cross validation and evaluated performance on an independent validation set. We assessed model interpretability with Shapley values.ResultsWe analyzed 1,539 cases and 1,431 controls; the independent validation set comprised 751 stays (~25%). A Random Forest classifier achieved an area under the receiver operating characteristic (AUROC) of 0.75 (95% CI, 0.72–0.79), a sensitivity of 0.74 (95% CI, 0.69–0.78), a specificity of 0.65 (95% CI, 0.60–0.70), a precision of 0.70 (95% CI, 0.66–0.74) and a F1 score of 0.72 (95% CI, 0.68–0.75) at the Youden’s index threshold. The model outperformed simple surrogates—mean blood pressure (AUROC, 0.68; 95% CI, 0.64–0.72) and modified shock index (AUROC, 0.65; 95% CI, 0.62–0.69)—and a reproduced bidirectional LSTM (AUROC, 0.73; 95% CI, 0.70–0.77). Key predictors included declining mean blood pressure at − 2 to −4 hours, elevated lactate ( > 2.5 mmol/L), and hematocrit outside 30–37%. Model alerts would occur two to four hours before vasopressor initiation, providing actionable lead time for clinicians.ConclusionsThis proof-of-concept study shows that routinely collected ICU data can predict impending vasopressor initiation with clinically interpretable outputs. However, these findings reflect internal validation only and should be interpreted with caution. External validation on multi-center retrospective cohorts, followed by silent-mode prospective evaluation, is warranted to confirm generalisability and to assess the real-world impact on time-to-vasopressor, fluid balance, and patient outcomes.Supplementary informationThe online version contains supplementary material available at 10.1186/s12911-025-03274-3.

Owing to faster identification of sepsis and improvement of patient management, most septic patients now survive the early phase of sepsis. Therefore, one of the major challenges in sepsis management today is to identify those patients at risk and propose effective personalized therapy. The complexity of the mechanisms involved in the septic immune response and its dysregulation is reflected in the diversity of immune profiles among sepsis patients. It is now well recognized that this heterogeneity is a major obstacle to stratifying patients based on their susceptibility to secondary infections. Since sepsis can originate from different anatomical sites, some studies have investigated their impact to decipher the heterogeneity. They concluded that the site of infection affects patient outcomes and leads to different immune alterations. This narrative review focuses on pulmonary sepsis to highlight the importance of studying organ response directly with local immune cells. Understanding the persistent dysregulation within the lung, whether it involves pulmonary immune cells or other lung components, is critical. Some studies have already examined the remodeling and loss of functionality of alveolar macrophages after the initial insult. Ongoing research is also investigating the impact of imbalances in other lung players, such as epithelial cells or the microbiota, on susceptibility to pulmonary reinfection.

Evaluating the impact of cardiac surgery on humoral and cellular immunity in pediatric congenital heart disease patients with prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection or vaccination is crucial for postoperative care planning. This study enrolled 61 pediatric patients undergoing cardiac surgery with cardiopulmonary bypass at a single institution. Measurements were taken before the operation, immediately postoperation, and during the first follow-up examination at least 1 month later. The evaluations included SARS-CoV-2-specific immunoglobulin G (IgG) and neutralizing antibodies for humoral immunity assessment, as well as specific and nonspecific T-cell immune responses to gauge T-cellular immunity and functionality. The results demonstrated that the serum titers of IgG and neutralizing antibodies remained comparable postsurgery to preoperative levels. Nevertheless, significant decreases in specific and nonspecific T-cell immune responses, along with a decline in CD3+ T-cell numbers, were observed immediately following surgery. This was followed by a gradual recovery of immune response to preoperative levels approximately 1 month later. These findings suggest that in the first month following cardiac surgery in pediatric patients, residual specific antibodies, potentially derived from the original production or plasma transfusion, may provide partial protection against COVID-19 infection. Subsequently, T-cellular immunity gradually recovers and resumes its protective role. The study provides important insights into the dynamics of immune recovery following cardiac surgery in this vulnerable patient population, which may be essential for optimizing postoperative management and reducing the risk of COVID-19 infection.

PurposeSeptic patients simultaneously experience hyperinflammation and immunosuppression, the latter driving ICU-acquired infections, prolonged stays in ICU, and increased mortality. As immunostimulant therapies enter clinical trials, effective stratification is critical to identify patients with the most profound immune dysfunction. Monocyte HLA-DR expression (mHLA-DR) has emerged as the most reliable and actionable biomarker of sepsis-induced immunosuppression.MethodsWe conducted a real-world, 20-year cohort study of 1023 septic shock patients, measuring mHLA-DR by standardized flow cytometry during the first week of ICU admission. Primary outcomes included day-28 and day-90 mortality, and ICU-acquired infections.ResultsLow mHLA-DR (< 8000 AB/C, a threshold already used in phase II trials) was significantly associated with increased mortality and ICU-acquired infections. This association held across static and dynamic measures, multivariate analyses, Kaplan–Meier survival curves, and trajectory clustering (K-means).ConclusionsThis large real-world study confirms that mHLA-DR is a robust enrichment biomarker for identifying the most immunosuppressed septic shock patients at higher risk of adverse outcomes. Importantly, time-course analysis suggests that early immune downregulation may represent a physiological adaptation, while delayed and persistent immunosuppression is associated with worse outcomes. Early single time-point measurements may fail to identify patients who are unlikely to develop delayed immunosuppression. Tracking mHLA-DR trajectories after the initial ICU days is essential for detecting persistent immune dysfunction and selecting patients in case of immunostimulant approaches.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00134-025-08110-w.

BackgroundPostoperative rectovaginal fistula leads to a loss of patients’ quality of life and presents significant challenges to the surgeon. The literature focusing specifically on postoperative rectovaginal fistulas is limited. The objective of the present study is to identify factors that can enhance the success of the management of this postoperative rectovaginal fistula.MethodsThis retrospective multicentric study included all patients undergoing surgery for rectovaginal fistulas, excluding those for whom the etiology of rectovaginal fistula was not postoperative. The major outcome measure was the success of the procedure.ResultsA total of 82 patients with postsurgical fistulas were identified, of whom 70 were successfully treated, giving a success rate of 85.4%. On average, these patients required 3.04 ± 2.72 interventions. The creation of a diversion stoma did not increase the success rate of management [odds ratio (OR) = 0.488; 95% confidence interval (CI) 0.107–2.220]. Among the 217 procedures performed, 69 were successful, accounting for a 31.8% success rate. The number of interventions and the creation of a diversion stoma did not correlate with the success of management. However, direct coloanal anastomosis was significantly associated with success (OR = 35.06; 95% CI 1.271–997.603; p = 0.036) as compared with endorectal advancement flap (ERAF). Other procedures such as Martius flap did not show a significantly higher success rate.ConclusionThe creation of a diversion stoma is not necessary in closing a fistula. ERAF should be considered as a first-line treatment prior to proposing more invasive approach such as direct coloanal anastomosis.