Regulatory T-cells and GARP expression are decreased in exercise-associated chikungunya viral arthritis flares.

Objective: Chikungunya virus (CHIKV) causes persistent arthritis, and our prior study showed that approximately one third of CHIKV arthritis patients had exacerbated arthritis associated with exercise. The underlying mechanism of exercise-associated chikungunya arthritis flare (EACAF) is unknown, and this analysis aimed to examine the regulatory T-cell immune response related to CHIKV arthritis flares. Methods: In our study, 124 Colombian patients with a history of CHIKV infection four years prior were enrolled and 113 cases with serologically confirmed CHIKV IgG were used in this analysis. Patient information was gathered via questionnaires, and blood samples were taken to identify total live peripheral blood mononuclear cells, CD4+ cells, T regulatory cells, and their immune markers. We compared outcomes in CHIKV patients with (n = 38) vs. without (n = 75) EACAF using t-tests to assess means and the Fisher's exact test, chi-squared to evaluate categorical variables, and Kruskal-Wallis tests in the setting of skewed distributions (SAS 9.3). Results: 33.6% of CHIKV cases reported worsening arthritis with exercise. EACAF patients reported higher global assessments of arthritis disease ranging from 0-100 (71.2 ± 19.7 vs. 59.9 ± 28.0, p=0.03). EACAF patients had lower ratios of T regulatory (Treg)/CD4+ T-cells (1.95 ± 0.73 vs. 2.4 ± 1.29, p = 0.04) and lower percentage of GARP (glycoprotein-A repetitions predominant) expression per Treg (0.13 ± 0.0.33 vs. 0.16 ± 0.24 p= 0.020). Conclusion: These findings suggest relative decreases in GARP expression may indicate a decreased level of immune suppression. Treg populations in patients with CHIKV arthritis may contribute to arthritis flares during exercise, though current research is conflicting.

Racial Disparities in 30-Day Outcomes After Colorectal Surgery in an Integrated Healthcare System.

BACKGROUND: Racial disparities in colorectal surgery outcomes have been studied extensively in the USA, and access to healthcare resources may contribute to these differences. The Veterans Health Administration (VHA) is the largest integrated healthcare network in the USA with the potential for equal access care to veterans. The objective of this study is to evaluate the VHA for the presence of racial disparities in 30-day outcomes of patients that underwent colorectal resection. METHODS: Colon and rectal resections from 2008 to 2019 were reviewed retrospectively using the Veterans Affairs Surgical Quality Improvement Program database. Patients were categorized by race and ethnicity. Multivariable analysis was used to compare 30-day outcomes. Cases with "unknown/other/declined to answer" race/ethnicity were excluded. RESULTS: Thirty-six-thousand-nine-hundred-sixty-nine cases met inclusion criteria: 27,907 (75.5%) Caucasian, 6718 (18.2%) African American, 2047 (5.5%) Hispanic, and 290 (0.8%) Native American patients. There were no statistically significant differences in overall complication incidence or mortality between all cohorts. Compared to Caucasian race, African American patients had longer mean length of stay (10.7 days vs. 9.7 days; p < 0.001). Compared to Caucasian race, Hispanic patients had higher odds of pulmonary-specific complications (adjusted odds ratio with 95% confidence interval = 1.39 [1.17-1.64]; p < 0.001). CONCLUSIONS: The VHA provides the benefits of integrated healthcare and access, which may explain the improvements in racial disparities compared to existing literature. However, some racial disparities in clinical outcomes still persisted in this analysis. Further efforts beyond healthcare access are needed to mitigate disparities in colorectal surgery. CLASSIFICATIONS: [Outcomes]; [Database]; [Veterans]; [Colorectal Surgery]; [Morbidity]; [Mortality].

Effect of Perioperative Transfusion on Postoperative Morbidity Following Minimally Invasive Hysterectomy for Benign Indications.

STUDY OBJECTIVE: To examine the impact of perioperative allogeneic blood transfusion (ABT) on postoperative infectious wound occurrences, sepsis-related events. and venous thromboembolism. DESIGN: Retrospective cohort study. SETTING: Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). PATIENTS: Patients who underwent a minimally invasive hysterectomy for benign indications between 2012 and 2016 were selected from the ACS-NSQIP. Patients with concurrent open hysterectomy, prolapse, or malignancy were excluded. Those with preoperative, intraoperative or postoperative red blood cell transfusion were considered positive for perioperative ABT. INTERVENTION: Minimally invasive hysterectomy for benign indications. MEASUREMENTS AND MAIN RESULTS: Univariate analyses were performed to determine associations of preoperative and intraoperative patient variables and postoperative outcomes with perioperative ABT. Multivariate analysis was completed to test the independent associations of perioperative ABT with outcomes while adjusting for possible confounders. Of the 90,231 patients who met our inclusion criteria, 1447 had a perioperative transfusion (1.6%). Perioperative ABT was associated with multiple preoperative variables. After multivariate analysis, perioperative ABT remained significantly associated with infectious wound events (adjusted odds ratio [aOR], 1.96; 95% confidence interval [CI], 1.9-2.58; p < .001), thromboembolic events (aOR, 2.75; 95% CI, 1.5-5.05; p = .001), and sepsis events (aOR, 6.49; 95% CI, 4.29-9.79, p < .001). CONCLUSION: ABT is a commonly used to treat perioperative anemia in patients undergoing gynecologic surgery. The results of this study, however, show that perioperative ABT increases a patient's risk of postoperative complications following minimally invasive hysterectomy. Gynecologic surgeons should consider the use of alternative treatments for perioperative anemia, including intravenous iron supplementation, erythropoiesis-stimulating agents, normovolemic hemodilution, and preoperative hormonal suppression, to help reduce the morbidity associated with perioperative ABT.

Gut Colonization with Methanogenic Archaea Lowers Plasma Trimethylamine N-oxide Concentrations in Apolipoprotein e-/- Mice.

A mechanistic link between trimethylamine N-oxide (TMAO) and atherogenesis has been reported. TMAO is generated enzymatically in the liver by the oxidation of trimethylamine (TMA), which is produced from dietary choline, carnitine and betaine by gut bacteria. It is known that certain members of methanogenic archaea (MA) could use methylated amines such as trimethylamine as growth substrates in culture. Therefore, we investigated the efficacy of gut colonization with MA on lowering plasma TMAO concentrations. Initially, we screened for the colonization potential and TMAO lowering efficacy of five MA species in C57BL/6 mice fed with high choline/TMA supplemented diet, and found out that all five species could colonize and lover plasma TMAO levels, although with different efficacies. The top performing MA, Methanobrevibacter smithii, Methanosarcina mazei, and Methanomicrococcus blatticola, were transplanted into Apoe-/- mice fed with high choline/TMA supplemented diet. Similar to C57BL/6 mice, following initial provision of the MA, there was progressive attrition of MA within fecal microbial communities post-transplantation during the initial 3 weeks of the study. In general, plasma TMAO concentrations decreased significantly in proportion to the level of MA colonization. In a subsequent experiment, use of antibiotics and repeated transplantation of Apoe-/- mice with M. smithii, led to high engraftment levels during the 9 weeks of the study, resulting in a sustained and significantly lower average plasma TMAO concentrations (18.2 ± 19.6 µM) compared to that in mock-transplanted control mice (120.8 ± 13.0 µM, p < 0.001). Compared to control Apoe-/- mice, M. smithii-colonized mice also had a 44% decrease in aortic plaque area (8,570 µm [95% CI 19587-151821] vs. 15,369 µm [95% CI [70058-237321], p = 0.34), and 52% reduction in the fat content in the atherosclerotic plaques (14,283 µm [95% CI 4,957-23,608] vs. 29,870 µm [95% CI 18,074-41,666], p = 0.10), although these differences did not reach significance. Gut colonization with M. smithii leads to a significant reduction in plasma TMAO levels, with a tendency for attenuation of atherosclerosis burden in Apoe-/- mice. The anti-atherogenic potential of MA should be further tested in adequately powered experiments.

Variation in Kidney Stone Composition Within the United States.

INTRODUCTION AND OBJECTIVES: Kidney stone incidence has been known to vary with temperature and climate. However, little is known about any variation in the composition of kidney stones across different regions of the United States. We attempted to evaluate whether stone composition changes depending on region. METHODS: We were given access to de-identified data from LABCORPs database of kidney stone composition from August 1, 2016, to October 24, 2016, for states in seven representative areas of the country: Virginia, Minnesota, Florida, Arizona, Colorado, California, and Texas. We analyzed each component of kidney stones with optical microscopy supplemented with Fourier-transform infrared spectroscopy (FT-IR) spectrometry using both the percentage of the stone that was composed of that component as well as a binary variable coded none vs any. Univariate associations between component and state were examined using chi-square or Fisher's exact test for the binary indicator, and analysis of variance for the continuous percentage. The same set of analyses was used for decade of age vs each component. The association between age and state was examined using analysis of variance. RESULTS: Data were available for 4335 kidney stones, from patients in the 7 states mentioned. The most common components across all stones were calcium oxalate monohydrate and calcium phosphate (both present in 93% of stones), calcium oxalate dihydrate (in 57% of stones), and uric acid (in 12% of stones). Stone composition did not vary widely across regions, except for uric acid stones, which were more prevalent in Florida compared to other states, with an odds ratio of 1.43 (95% confidence interval 1.12, 1.83). CONCLUSION: Kidney stone composition does not vary widely by region within the United States. Although temperature and humidity play a role in stone incidence, there does not appear to be a large variation between different climates, with the exception of uric acid stone formation in Florida.

Follow-up after gastric electrical stimulation for gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) is used to treat medically refractory gastroparesis. However, there are few large series with outcomes beyond 12 months. This study reports surgical outcomes of GES for patients up to 8 years receiving treatment from a single institution. STUDY DESIGN: A prospective database was reviewed from 2003 to 2013 for patients undergoing GES. Baseline patient characteristics were recorded, including age, sex, cause of gastroparesis, gastric emptying, and Hgb A1C. Outcomes variables included nutrition supplementation, additional operations, 30-day morbidity, and mortality. Pre- and postoperative pain and function scores are analyzed over time using generalized estimating equations. Patient outcomes in terms of reoperation rates and types of operations are also reviewed. RESULTS: Seventy-nine patients underwent GES with a mean ± SD age of 43 ± 11 years and a BMI of 27 ± 8 kg/m(2). Symptom scores were available for 60 patients: 60 patients at baseline, 52 patients at 1 year, 14 patients during years 2 to 3, and 18 patients during years 4 to 8. Symptom scores decreased considerably in all categories. At 1-year follow-up, 44% and 31% of patients had at least a 25% reduction in symptom distress for functional and pain symptoms, respectively. Preoperatively, 9 patients required nutrition supplementation. After implantation, 34 (43%) patients underwent additional operations, with a mean of 2.15 operations per patient. Generator-related causes were the most common indication for reoperation, including battery exchanges and relocation. Other operations included 8 gastrectomies and 7 median arcuate ligament releases. Postoperatively, 4 patients required supplemental nutrition. There were no 30-day mortalities, but 11 patients died during the study period. CONCLUSIONS: Gastric electrical stimulation was significantly associated with reductions in both functional and pain-related symptoms of gastroparesis. Patients who undergo GES have a high likelihood of additional surgery.