Towards personalized medicine: a scoping review of immunotherapy in sepsis.

Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy.

Protocol for a systematic review and meta-analysis investigating the impact of continuous versus intermittent enteral feeding in critically ill patients.

INTRODUCTION: Enteral nutrition (EN) is the recommended nutritional support in most critically ill populations. When given by feeding tube, EN may be administered either continuously or intermittently. It is unclear which approach is superior in reducing gastrointestinal complications-such as diarrhea-and meeting nutritional targets. The main objectives of this systematic review and meta-analysis are to (1) determine whether continuous or intermittent enteral nutrition is associated with higher incidence of adverse gastrointestinal outcomes, including diarrhea, and (2) determine which feeding modality is associated with reaching nutritional goals. METHODS AND ANALYSIS: This systematic review protocol is reported in accordance with guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement. We will search MEDLINE, Embase, the Cochrane Library, and the World Health Organization (WHO) International Clinical Trials Registry (ICTRP) search portal for studies comparing continuous EN and intermittent EN in critically ill patients with no date or language restrictions. Studies will be screened, selected, and extracted independently and in duplicate. We will assess the risk-of-bias assessment using the Cochrane Collaboration's Risk of Bias (RoB) 2 tool. The primary outcome will include the incidence of diarrhea; secondary outcomes include other adverse GI outcomes (nausea, vomiting, abdominal pain, and constipation), as well as reaching nutritional goals, and length of ICU and hospital stay and mortality. We will pool data using a random-effects model and assess the certainty of the evidence for each outcome using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. ETHICS AND DISSEMINATION: Ethics approval is not required for this study as no original data will be collected. We will disseminate results through peer-reviewed publication and conference presentations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022330118.