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Background: Obesity is associated with increased morbidity and mortality in trauma scenarios; however, there has been conflicting evidence on outcomes of obesity and penetrating injuries, specifically gunshot wounds and stab wounds. We hypothesized that obesity may be protective due to a "cushioning effect" attributed to increased adiposity. Methods: This was a retrospective cohort study of patients presenting to a Level 1 Trauma Center with a penetrating trauma (gunshot/stab) injury during 2008-2021. Patients with a BMI ≥ 30 were compared to those with a BMI < 30. The primary outcome was Injury Severity Score (ISS). Secondary outcomes included intensive care unit (ICU) length of stay, days on ventilation, length of hospital stay, service of admission (trauma surgery, general surgery, discharged home, general medical floor), the body region of injury(s), Abbreviated Injury Scale (AIS), OR requirement, type of surgery, and discharge status. Statistical analysis was performed using χ2-test or Fisher's exact tests for categorical data, and Student's t-test or Mann-Whitney U-test for continuous variables with p < 0.05 as statistically significant. Subgroup analysis was performed based on the mechanism of injury. Results: There were 721 patients that met inclusion criteria, of which 540 were classified in the non-obese group and 181 (25.1%) in the obese group. The primary outcome, mean ISS score, in obese patients (9.0, SD = 13.0) and non-obese patients (9.4, SD = 13.8) was similar between groups respectively. Secondary outcomes, which included rates of severe abdominal injury (AIS ≥ 3), rates of intra-abdominal organ injury, and rates of gastro-intestinal resection, were also similar between non-obese and obese patients. Conclusion: This study did not demonstrate the existence of a "cushioning effect" in the setting of penetrating traumatic injury. Patients with increased BMI had similar a ISS score and patterns of injury as their non-obese counterparts.
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BACKGROUND: Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. A subset of these patients possess defects in natural killer (NK) cells, lymphocytes that recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK-cell and B-cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported to date. OBJECTIVES: The investigators aimed to identify the genetic cause of NK-cell immunodeficiency in 2 families and herein describe the functional consequences of 2 novel loss-of-function variants in PLCG2. METHODS: The investigators employed whole-exome sequencing in conjunction with mass cytometry, microscopy, functional assays, and a mouse model of PLCG2 haploinsufficiency to investigate 2 families with NK-cell immunodeficiency. RESULTS: The investigators identified novel heterozygous variants in PLCG2 in 2 families with severe and/or recurrent herpesvirus infections. In vitro studies demonstrated that these variants were loss of function due to haploinsufficiency with impaired NK-cell calcium flux and cytotoxicity. In contrast to previous PLCG2 variants, B-cell function remained intact. Plcg2+/- mice also displayed impaired NK-cell function with preserved B-cell function, phenocopying human disease. CONCLUSIONS: PLCG2 haploinsufficiency represents a distinct syndrome from previous variants characterized by NK-cell immunodeficiency with herpesvirus susceptibility, expanding the spectrum of PLCG2-related disease.