Small Bowel Obstruction Following Congenital Diaphragmatic Hernia Repair-Incidence and Risk Factors.

BACKGROUND: Small bowel obstruction (SBO) is a known complication following congenital diaphragmatic hernia (CDH) repair, resulting in significant morbidity and potential mortality. Our study aims to evaluate the incidence and risk factors for SBO following CDH repair. METHODS: A single-institution retrospective review evaluated all CDH births between January 2010 and September 2022 (n = 120). Risk factors for SBO were analyzed, including operative approach, type of repair, need for extracorporeal membrane oxygenation (ECMO), and additional abdominal surgeries (gastrostomy tube and fundoplication). RESULTS: 120 patients were included. 16 (13%) patients developed an SBO, of which 94% were due to adhesive bands. The median time to SBO was 7.5 months. 15/16 (94%) patients required operative intervention. Need for ECMO (P < 0.01), prior gastrostomy tube (P < 0.01), and prior fundoplication (P < 0.01) were associated with an increased risk of SBO, as were longer time to initial CDH repair (6 days vs 3 days; P < 0.01) and longer length of initial hospitalization (63 days vs 29 days; P = 0.01). DISCUSSION: Neonates with increased acuity of illness (ie, those requiring ECMO, additional abdominal operations, longer time to repair, and longer initial hospitalizations) appear to have an increased risk of developing adhesive SBO after CDH repair. More than 90% of patients who developed SBO required surgery.

Cerebrospinal fluid immunoglobulins in primary progressive multiple sclerosis are pathogenic.

Multiple sclerosis is clinically characterized by relapses and remissions (relapsing-remitting multiple sclerosis) that over time may evolve to a progressive course (secondary progressive multiple sclerosis) or as having a progressive course from disease onset (primary progressive multiple sclerosis). At present, it is not definitively known whether these clinical entities constitute a single pathological disease or whether these manifestations represent two distinct disease entities sharing inflammatory demyelination as a pathological feature. Here we show using a novel mouse model that CSF of primary progressive multiple sclerosis patients is unique in its capacity to induce motor disability and spinal cord pathology including demyelination, impaired remyelination, reactive astrogliosis and axonal damage. Notably, removal of immunoglobulin G from primary progressive multiple sclerosis CSF via filtration or immunodepletion attenuates its pathogenic capacity. Furthermore, injection of recombinant antibodies derived from primary progressive multiple sclerosis CSF recapitulates the pathology. Our findings suggest that the clinical and pathological features of primary progressive multiple sclerosis are antibody-mediated and pathogenically distinct from relapsing-remitting and secondary progressive multiple sclerosis. Our study has potentially important implications for the development of specific therapies for patients with primary progressive multiple sclerosis.

Multiplex Quantification Identifies Novel Exercise-regulated Myokines/Cytokines in Plasma and in Glycolytic and Oxidative Skeletal Muscle.

Exercise is known to confer major health benefits, but the underlying mechanisms are not well understood. The systemic effects of exercise on multi-organ systems are thought to be partly because of myokines/cytokines secreted by skeletal muscle. The extent to which exercise alters cytokine expression and secretion in different muscle fiber types has not been systematically examined. Here, we assessed changes in 66 mouse cytokines in serum, and in glycolytic (plantaris) and oxidative (soleus) muscles, in response to sprint, endurance, or chronic wheel running. Both acute and short-term exercise significantly altered a large fraction of cytokines in both serum and muscle, twenty-three of which are considered novel exercise-regulated myokines. Most of the secreted cytokine receptors profiled were also altered by physical activity, suggesting an exercise-regulated mechanism that modulates the generation of soluble receptors found in circulation. A greater overlap in cytokine profile was seen between endurance and chronic wheel running. Between fiber types, both acute and chronic exercise induced significantly more cytokine changes in oxidative compared with glycolytic muscle. Further, changes in a subset of circulating cytokines were not matched by their changes in muscle, but instead reflected altered expression in liver and adipose tissues. Last, exercise-induced changes in cytokine mRNA and protein were only minimally correlated in soleus and plantaris. In sum, our results indicate that exercise regulates many cytokines whose pleiotropic actions may be linked to positive health outcomes. These data provide a framework to further understand potential crosstalk between skeletal muscle and other organ compartments.