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BACKGROUND: Sepsis is a life-threatening syndrome with complex pathophysiology and great clinical heterogeneity which complicates the delivery of personalized therapies. Our goals were to demonstrate that some biomarkers identified as regulatory immune checkpoints in preclinical studies could 1)improve sepsis prognostication based on clinical variables and 2)guide the stratification of septic patients in subgroups with shared characteristics of immune response or survival outcomes. METHODS: We assayed the soluble counterparts of 12 biomarkers of immune response in 113 internal medicine patients with bacterial sepsis. RESULTS: IL-1 receptor-associated kinase M (IRAK-M) exhibited the highest hazard ratios (HRs) for increased 7-day (1.94 [1.17-3.20]) and 30-day mortality (1.61 [1.14-2.28]). HRs of IRAK-M and Galectin-1 for predicting 1-year mortality were 1.52 (1.20-1.92) and 1.64 (1.13-2.36), respectively. A prognostic model including IRAK-M, Galectin-1, and clinical variables (Charlson Comorbidty Index, multiple source of sepsis, and SOFA score) had high discrimination for death at 7 days and 30 days (area under the curve 0.90 [0.82-0.99]) and 0.86 [0.79-0.94], respectively). Patients with elevated serum levels of IRAK-M and Galectin-1 had clinical traits of immune suppression and low survival rates. None of the 12 biomarkers were independent predictors of 2-year mortality. CONCLUSIONS: Two inhibitory immune checkpoint biomarkers (IRAK-M and Galectin-1) helped identify 3 distinct sepsis phenotypes with distinct prognoses. These biomarkers shed light on the interplay between immune dysfunction and prognosis in patients with bacterial sepsis and may prove to be useful prognostic markers, therapeutic targets, and biochemical markers for targeted enrollment in targeted therapeutic trials.
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INTRODUCTION: Data on seizure course during pregnancy in women with epilepsy are limited. In particular, little is known about the causes underlying possible seizure worsening in this population. We therefore set out to explore worsening, in pregnancy, of sleep-related hypermotor epilepsy (SHE), a syndrome in which seizures are known to be triggered by sleep fragmentation, a condition common in pregnancy. METHODS: From a cohort of consecutive patients with epilepsy who had one or more deliveries between January 2008 and March 2018, we retrospectively compared the rates of seizure worsening during pregnancy in SHE versus other epilepsies (NSHE). Worsening was defined as an increase in seizure frequency compared with the rate for the year prior to conception, including seizure recurrence after a year of seizure freedom, and/or new occurrence of tonic-clonic seizures. RESULTS: We considered data on 11 pregnancies in women with SHE and 104 pregnancies in women with NSHE. Seizures worsened in six SHE pregnancies (54.5%) versus 18 NSHE ones (17.3%) (OR adjusted for preconception seizure frequency and polytherapy = 5.7, 95% CI = 1.6-20.8, p = 0.019). CONCLUSIONS: Women with SHE have a higher risk of seizure worsening in pregnancy. This finding should be considered from the perspective of patient counseling.