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Background Necrotizing soft tissue infections (NSTI) represent a heterogeneous group of rapidly progressive skin and soft tissue infections associated with significant morbidity and mortality. Efforts to identify factors associated with death have produced mixed results, and little or no data is available for other adverse outcomes. We sought to determine whether admission variables were associated with mortality, limb loss, and discharge disposition in patients with NSTI. Methods We analyzed prospectively collected data of adult patients with surgically confirmed NSTI from an NSTI registry maintained at a quaternary referral center. Factors independently associated with mortality, amputation, and skilled nursing facility discharge were identified using logistic regression. Results Between 2015 and 2018, 446 patients were identified. The median age was 55 years (interquartile range, 43-62). The majority of patients were male (65%), white (77%), and transferred from another facility (90%). The perineum was most commonly involved (37%), followed by the lower extremity (34%). The median number of operative debridements was 3 (interquartile range, 2-4). Overall mortality was 15%, and 21% of extremity NSTI patients required amputation. Age greater than 60 years; creatinine greater than 2 mg/dL; white blood cell count greater than 30 x 10^ /μl, platelets less than 150 × 10/μL, and clostridial involvement were independently associated with greater odds of death; perineal involvement was associated with lower odds of death. Age greater than 60 years; sex, male; nonwhite race; diabetes; chronic wound as etiology; leg involvement; transfer status; and sodium, less than 130 mEq/L were independently associated with amputation. Age greater than 60 years; sex, female; nonwhite race; perineal involvement; and amputation were associated with skilled care facility discharge. Conclusion Necrotizing soft tissue infections are a heterogeneous group of infections involving significantly different patient populations with different outcomes; efforts to differentiate and predict adverse outcomes in NSTI should include laboratory data, comorbidities, infection site, and/or etiology to improve predictions and better account for this heterogeneity. Level of evidence Prognostic, Level III.

Objective Determine whether variation in the HLA region is associated with the development of post-traumatic sepsis and septic shock. Background Sepsis-related deaths remain a major source of mortality after traumatic injury. Genetic characteristics may contribute to susceptibility to adverse outcomes including sepsis and septic shock. Recent advances in next-generation sequencing technology now allow comprehensive genotyping of the HLA region. Methods White adult trauma patients requiring more than 2 days of mechanical ventilation underwent HLA genotyping, and were followed for the development of sepsis and septic shock. Odds ratios (OR) for the associations between our outcomes and HLA variants were estimated, a correction for multiple comparisons was applied, and significant variants were included in regression models adjusting for potential confounders. Results A total of 1184 patients were included. Patients were severely injured (median injury severity score 33); 33% developed sepsis, 6% septic shock, and in-hospital mortality was 14%. An amino acid variant (156Q) within the HLA-A peptide-binding groove was associated with greater odds of sepsis [OR 1.50, (1.18-1.89)]. HLA-A02:01 was associated with lower odds of septic shock [OR 0.52, (0.32-0.82)]. These associations remained significant after adjusting for potential confounders. Conclusions This is the first study to apply next-generation sequencing techniques to evaluate associations between immunogenetic factors and post-traumatic sepsis and septic shock. Associations with class I HLA variants are novel as they implicate adaptive immunity in post-traumatic sepsis. These findings are a step towards developing a panel of genetic markers assessing risk of infection-related complications as we move towards more personalized medicine.

BACKGROUND: Following trauma, persistent inflammation, immunosuppression, and catabolism may characterize delayed recovery or failure to recover. Understanding the metabolic response associated with these adverse outcomes may facilitate earlier identification and intervention. We characterized the metabolic profiles of trauma victims who died or developed chronic critical illness (CCI) and hypothesized that differences would be evident within 1-week postinjury. METHODS: Venous blood samples from trauma victims with shock who survived at least 7 days were analyzed using mass spectrometry. Subjects who died or developed CCI (intensive care unit length of stay of ≥14 days with persistent organ dysfunction) were compared with subjects who recovered rapidly (intensive care unit length of stay, ≤7 days) and uninjured controls. We used partial least squares discriminant analysis, t tests, linear mixed effects regression, and pathway enrichment analyses to make broad comparisons and identify differences in metabolite concentrations and pathways. RESULTS: We identified 27 patients who died or developed CCI and 33 who recovered rapidly. Subjects were predominantly male (65%) with a median age of 53 years and Injury Severity Score of 36. Healthy controls (n = 48) had similar age and sex distributions. Overall, from the 163 metabolites detected in the samples, 56 metabolites and 21 pathways differed between injury outcome groups, and partial least squares discriminant analysis models distinguished injury outcome groups as early as 1-day postinjury. Differences were observed in tryptophan, phenylalanine, and tyrosine metabolism; metabolites associated with oxidative stress via methionine metabolism; inflammatory mediators including kynurenine, arachidonate, and glucuronic acid; and products of the gut microbiome including indole-3-propionate. CONCLUSIONS: The metabolic profiles in subjects who ultimately die or develop CCI differ from those who have recovered. In particular, we have identified differences in markers of inflammation, oxidative stress, amino acid metabolism, and alterations in the gut microbiome. Targeted metabolomics has the potential to identify important metabolic changes postinjury to improve early diagnosis and targeted intervention. LEVEL OF EVIDENCE: Prognostic/epidemiologic, level III.

Firearm storage method is a potentially modifiable risk factor for suicide. Using data from a large, multi-state survey, we sought to determine whether there is an association between mental health and household firearm storage practices, and characterize that association by state of residence. Participants who endorsed the presence of a household firearm and answered the mental health questions in the 2016–2017 Behavioral Risk Factor Surveillance System from eight states were included (n=26,949). Exposures were recent poor mental health (≥14 vs. 0–13 days/past month), and diagnosis of depression. Outcomes were household firearm storage practices (loaded, and both loaded and unlocked). Using Poisson regression, we calculated adjusted prevalence ratios (aPR) overall and stratified by state of residence. Of adults endorsing a household firearm, 35.1% reported storing a firearm loaded, and of those, 53.4% reported that the firearm was both loaded and unlocked. Neither recent poor mental health nor depression was associated with loaded (aPR 1.14 [95% CI: 0.95–1.37] and aPR 0.94 [95% CI 0.80–1.09], respectively) or loaded and unlocked (aPR 1.08 [95% CI 0.88–1.42] and aPR 1.04 [95% CI 0.88–1.22], respectively) firearm storage. In the setting of highly prevalent loaded firearm storage, no differences in storage practices by mental health indicators were observed across eight states despite disparate firearm policies and local culture. The lack of difference in storage practices by mental health indicators across several states highlights an opportunity to improve means safety counseling practices, and the need for dedicated evaluation of state-level firearm storage policies.

Background β-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. Methods Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of β-hemolytic streptococci or clindamycin-resistant β-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use–related etiology. Results Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. β-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of β-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07–3.01), as was the presence of clindamycin resistance among β-hemolytic streptococci infections (1.86; 1.10–3.16). Conclusions β-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with β-hemolytic streptococci—particularly clindamycin-resistant strains—may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.

Background Transversus abdominis release is a novel approach for myofascial advancement in ventral hernia repair and has been hypothesized to have lower rates of wound complication than anterior component separation. Methods Patients who had a ventral hernia repair with either transversus abdominis release or minimally invasive anterior component separation from January of 2010 to January of 2016 were enrolled in this retrospective cohort study. Patient characteristics were collected through chart review. Primary outcomes were operative time and wound complications. Multiple linear/Poisson regression and Fisher's exact test were used to determine statistical significance. Results Of 142 patients analyzed, 75 subjects underwent Butler minimally invasive anterior component separation and 67 underwent transversus abdominis release. There were no differences in baseline characteristics between groups, except that the anterior component separation group had more immunosuppressed patients (35 percent versus 19 percent). Median operative time for anterior component separation was 6.3 hours versus 6.1 hours for transversus abdominis release (p = 0.6). Overall wound complications did not differ between the groups (p = 0.5). Compared with anterior component separation, transversus abdominis release had a similar incidence of seroma/hematoma (relative risk, 0.9; 95 percent CI, 0.5 to 1.7), wound infection (relative risk, 1.1; 95 percent CI, 0.5 to 2.2), and mesh infection (relative risk, 0.7; 95 percent CI, 0.2 to 3.4). Hernia recurrence was 12 percent for anterior component separation and 6 percent for transversus abdominis release (relative risk, 0.6; 95 percent CI, 0.2 to 1.7). Reoperation was required in 19 percent of anterior component separation and 12 percent of transversus abdominis release subjects (relative risk, 0.5; 95 percent CI, 0.2 to 1.2). Conclusions Transversus abdominis release patients had similar operative times, wound complications, reoperations, and hernia recurrences compared with Butler minimally invasive anterior component separation patients. This contemporary comparison helps inform operative decisions for reconstructive surgeons. Clinical question/level of evidence Therapeutic, III.

Here we present a case series from a primate research facility. The index case, a 4-year-old pig-tailed macaque (Macaca nemestrina) experimentally infected with chimeric simian-human immunodeficiency virus (SHIVSF162 P4), developed weight loss and was euthanized. Based on necropsy results the animal was diagnosed with opportunistic atypical mycobacteriosis associated with simian AIDS (SAIDS). Subsequently, tissues from the index animal, as well as tissues and oral mucosal swabs from six SHIV-infected contacts, were analyzed using molecular methods and found to contain nucleic acid sequences characteristic of Mycobacterium tuberculosis complex (MTBC). These data suggest that existing protocols fail to reliably detect MTBC infection in laboratory primates used as experimental models.