Obstetric neuraxial anesthesia at low platelet counts in the context of immune thrombocytopenia: a systematic review and meta-analysis.

PURPOSE: Primary immune thrombocytopenia (ITP) is an autoimmune condition affecting women of childbearing age that is characterized by diminished platelet quantity with preserved function. Although pregnant women with ITP are often denied obstetric neuraxial anesthesia (OBNA) with low platelet counts for fear of neuraxial hematoma, the true magnitude of neuraxial hematoma for ITP parturients is unknown. The aim of this systematic review and meta-analysis was to examine OBNA outcomes in ITP parturients with platelet counts below 100 x 109·L-1. SOURCE: Articles published in MEDLINE, Embase, Web of Science, Scopus, Cochrane, and PubMed in process until May 14, 2018 were searched. Two reviewers independently screened 954 articles by title and abstract, reviewed 62 full-texts, extracted data, and assessed risk of bias for 26 articles. PRINCIPAL FINDINGS: Of 291 pregnant women with ITP and platelet counts below 100 x 109·L-1, 166 received OBNA and 61 of these had platelet counts below 80 x 109·L-1. No neuraxial hematomas were reported. Meta-analysis of six studies showed higher platelet counts in those with OBNA than without (mean difference [MD], 19 x 109·L-1; 95% confidence interval [CI], 11 to 26; P < 0.001), with no difference between epidural and spinal anesthesia (MD, 0.4 x 109·L-1; 95% CI, -4 to 4; P = 0.86). CONCLUSION: Our study highlights continued reluctance to offer OBNA below the commonly quoted 80 x 109·L-1 platelet count, based largely on consensus and theoretical presumption of risk. This further negatively influences the accrual of large-scale data. The evidence of no neuraxial hematoma after OBNA provided herein offers support for considering neuraxial anesthesia at lower platelet count thresholds. Each patient should be afforded individualized discussion of risk and benefit relative to other analgesic measures. TRIAL REGISTRATION: PROSPERO (CRD42018059220); registered 2 August, 2018.

Mice lacking NOX2 are hyperphagic and store fat preferentially in the liver.

Chronic low-grade inflammation is an important contributor to the development of insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Obesity and high-fat feeding lead to infiltration of immune cells into metabolic tissues, promoting inflammation and insulin resistance. We hypothesized that macrophages from mice lacking NOX2 (Cybb), an essential component of the NADPH oxidase complex highly expressed in immune cells and associated with their inflammatory response, would be less inflammatory and that these mice would be protected from the development of high-fat-induced insulin resistance. Bone marrow-derived macrophages from NOX2 knockout (NOX2-KO) mice expressed lower levels of inflammatory markers (Nos2, Il6); however, NOX2-KO mice were hyperphagic and gained more weight than wild-type (WT) mice when fed either a chow or a high-fat (HF) diet. Surprisingly, NOX2-KO mice stored less lipid in epididymal white adipose tissue but more lipid in liver and had higher indexes of liver inflammation and macrophage infiltration than WT mice. Contrary to our hypothesis, HF-fed NOX2-KO mice were hyperinsulinemic and more insulin resistant than HF-fed WT mice, likely as a result of their higher hepatic steatosis and inflammation. In summary, NOX2 depletion promoted hyperphagia, hepatic steatosis, and inflammation with either normal or high-fat feeding, exacerbating insulin resistance. We propose that NOX2 participates in food intake control and lipid distribution in mice.