Consumption of sucralose- and acesulfame-potassium-containing diet soda alters the relative abundance of microbial taxa at the species level: findings of two pilot studies.

Sucralose and acesulfame-potassium consumption alters gut microbiota in rodents, with unclear effects in humans. We examined effects of three-times daily sucralose- and acesulfame-potassium-containing diet soda consumption for 1 (n = 17) or 8 (n = 8) weeks on gut microbiota composition in young adults. After 8 weeks of diet soda consumption, the relative abundance of Proteobacteria, specifically Enterobacteriaceae, increased; and, increased abundance of two Proteobacteria taxa was also observed after 1 week of diet soda consumption compared with sparkling water. In addition, three taxa in the Bacteroides genus increased following 1 week of diet soda consumption compared with sparkling water. The clinical relevance of these findings and effects of sucralose and acesulfame-potassium consumption on human gut microbiota warrant further investigation in larger studies. Clinical trial registration: NCT02877186 and NCT03125356.

Ligamentum teres cardiopexy for post vertical sleeve gastrectomy gastroesophageal reflux.

PURPOSE: Vertical sleeve gastrectomy (VSG) evolved in the early 2000s into the standalone weight loss procedure we see today. While numerous studies highlight VSG's durability for weight loss, and improvements co-morbidities such as type 2 diabetes mellitus and cardiovascular disease, patients with gastroesophageal reflux disease (GERD) have been counseled against VSG due to the concern for worsening reflux symptoms. When considering anti-reflux procedures, VSG patients are unable to undergo traditional fundoplication due to lack of gastric cardia redundancy. Magnetic sphincter augmentation lacks long-term safety data and endoscopic approaches have undetermined longitudinal benefits. Until recently, the only option for patients with a history of VSG with medically refractory GERD has been conversion to roux en Y gastric bypass (RNYGB), however, this poses other risks including marginal ulcers, internal hernias, hypoglycemia, dumping syndrome, and nutritional deficiencies. Given the risks associated with conversion to RNYGB, we have adopted the ligamentum teres cardiopexy as an option for patients with intractable GERD following VSG. METHODS: A retrospective chart review was conducted of patients who had prior laparoscopic or robotic VSG and subsequently GERD symptoms refectory to pharmacological management who underwent ligamentum teres cardiopexy between 2017 and 2022. Pre-operative GERD disease burden, intraoperative cardiopexy characteristics, post-operative GERD symptomatology and changes in H2 blocker or PPI requirements were reviewed. RESULTS: Of the study's 60 patients the median age was 50 years old, and 86% were female. All patients had a diagnosis of GERD through pre-operative assessments and were taking antisecretory medication. Of the 36 patients who have completed their one year follow up, 81% of patients had either a decrease in dosage or cessation of the antisecretory medication at one year following ligamentum teres cardiopexy. CONCLUSION: Ligamentum teres cardiopexy is a viable alternative to RNYGB in patients with a prior vertical sleeve gastrectomy with medical refractory GERD.

Use of medical chaperones by colon and rectal surgeons in outpatient practice.

BACKGROUND: The purpose of this study is to determine the frequency and motivations for medical chaperone use during anorectal exams by colon and rectal surgeons in the outpatient setting. STUDY DESIGN: This cross-sectional study examined factors impacting chaperone use via an anonymous online survey distributed via the American Society of Colon and Rectal Surgeons email list. Routine chaperone use was defined as ≥ 90%. RESULTS: Of 1,380 emailed board-certified colon and rectal surgeons, 402 (29.1%) completed the survey in November 2019. Median years in practice was 14, and 72.3% were male. Overall, 65.2% reported routine use of chaperones during anorectal exams. Over half (56.3%) felt chaperones should be mandatory and were more likely to report routine use than those who did not (85.7 vs. 39.1%; p < 0.001). Only 23.7% reported that their institutions had formal chaperone policies. The most common reason for use was medicolegal (91.8%), and the most common barrier was chaperone availability (56.7%). When chaperones were used, 42% did not document use in the medical record. On multivariable analysis, increased odds of routine chaperone use were independently associated with: being ≤ 10 years in practice, routine chaperone use during fellowship, and chaperones being routinely available. CONCLUSION: Half of surgeons felt that chaperones should be mandatory, suggesting lack of consensus among the cohort. Despite expressing legal concerns, one-third did not use chaperones and nearly half who used chaperones did not document their use. Efforts to improve chaperone availability, documentation of chaperone use, and knowledge of policies are necessary.

Twitter Use Among Departments of Surgery With General Surgery Residency Programs.

OBJECTIVE: To examine patterns of Twitter use by surgery departments with residency programs and understand relevant motivations and concerns. The primary outcome was to quantify account prevalence and activity. The secondary outcomes were to identify reasons for use and perceived benefits and concerns. DESIGN SETTING, AND PARTICIPANTS: A cross-sectional study was performed on Twitter accounts of departments of surgery with Accreditation Council of Graduate Medical Education accredited general surgery residencies. An anonymous survey was distributed to all programs with accounts. Data acquisition was completed in August 2019 and analysis was completed in February 2020. RESULTS: Among the 319 departments of surgery, only 80 (25%) had department of surgery Twitter accounts. Mean account age was 3.5 years (range: 0-9.8), with the highest account creation in 2017 (n = 23, 29%). Median total tweets per account was 314 (range 3-21,893), and median number of followers was 454 (range 18-22,353). Having a Twitter account was associated with program type: 66/123 (54%) university-based, 1/9 (11%) military, 13/124 (11%) community/university-affiliated, and 0/63 (0%) community (p < 0.01). Survey response rate was 40% (n = 32). Only 59% had formal posting guidelines. Daily logins (78%) and daily tweeting (53%) were common. The most frequent perceived benefits were "highlighting new research and major events" (97%), "increasing visibility within the academic community" (91%), and "improving resident engagement" (75%). The most common concerns were "professionalism" (72%), "privacy" (63%), and "time commitment" (53%). CONCLUSIONS: Though only a quarter of departments of general surgery had Twitter accounts, they were felt to be key for improving academic reach. Formal posting guidelines existed for 59% of survey respondents, although concerns about privacy and content were common. An underutilized tool for surgery departments to promote academic achievements, Twitter use represents a potential opportunity to engage the surgical community more broadly.

Linagliptin, when compared to placebo, improves CD34+ve endothelial progenitor cells in type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin: a randomized controlled trial.

BACKGROUND: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP4 inhibitors such as linagliptin (LG) on CVD risk, in patients with T2DM with established CKD has not been established. Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) population. METHODS: 31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 diabetes subjects (30-70 years old), HbA1c of 6.5-10%, CKD Stage 1-3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value < 0.05 considered significant. RESULTS: A double positive CD34/CD184 cell count had a statistically significant increase (p < 0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p < 0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p < 0.04). Urinary exosome protein examining podocyte health (podocalyxin, Wilms tumor and nephrin) showed reduction or improvement. CONCLUSIONS: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34 + progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks. Trial Registration Number NCT02467478 Date of Registration: 06/08/2015.

Consumption of Diet Soda Sweetened with Sucralose and Acesulfame-Potassium Alters Inflammatory Transcriptome Pathways in Females with Overweight and Obesity.

SCOPE: Low-calorie sweetener (LCS) consumption is associated with metabolic disease in observational studies. However, physiologic mechanisms underlying LCS-induced metabolic impairments in humans are unclear. This study is aimed at identifying molecular pathways in adipose impacted by LCSs. METHODS AND RESULTS: Seven females with overweight or obesity, who did not report LCS use, consumed 12 ounces of diet soda containing sucralose and acesulfame-potassium (Ace-K) three times daily for 8 weeks. A subcutaneous adipose biopsy from the left abdomen and a fasting blood sample were collected at baseline and post-intervention. Global gene expression were assessed using RNA-sequencing followed by functional pathway analysis. No differences in circulating metabolic or inflammatory biomarkers were observed. However, ANOVA detected 828 differentially expressed annotated genes after diet soda consumption (p < 0.05), including transcripts for inflammatory cytokines. Fifty-eight of 140 canonical pathways represented in pathway analyses regulated inflammation, and several key upstream regulators of inflammation (e.g., TNF-alpha) were also represented. CONCLUSION: Consumption of diet soda with sucralose and Ace-K alters inflammatory transcriptomic pathways (e.g., NF-κB signaling) in subcutaneous adipose tissue but does not significantly alter circulating biomarkers. Findings highlight the need to examine molecular and metabolic effects of LCS exposure in a larger randomized control trial for a longer duration.

Reassessing the effects of continuous positive airway pressure (CPAP) on arterial stiffness and peripheral blood derived CD34+ progenitor cells in subjects with sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular diseases (CVD) and vascular health. Peripheral blood-derived CD34+ progenitor cells have been used as biomarker for CVD risk and may play a similar role in OSA and CVD risk assessment. Although there are some controversial results in the literature, OSA patients may have a reduction in the number and function of CD34+ cells. The damages promoted by OSA in CD34+ cells may lead to an increase in endothelial oxidative stress and endothelial inflammation which may lead to a reduced endothelial repair capacity. In this study, we explored the effect of continuous positive airway pressure (CPAP) on peripheral blood-derived CD34+ cells and arterial stiffness (another predictor of endothelial health and CVD risk) in OSA patients. METHODS AND RESULTS: Nine overweight and obese subjects without prediabetes or diabetes were recruited. Eight out of nine subjects had moderate to severe degree of OSA. CD34+ cells were isolated from peripheral blood. Number and function of these cells were monitored before and after 3 months of treatment with CPAP. No significant changes were observed in the number of CD34+ cells, CFU-Hill's colony formation unit (CFU) count or migratory response to the chemotactic factor SDF-1a after CPAP use. However, CXCR4 mRNA expression significantly increased by 2.2-fold indicating that CPAP may have a positive effect on SDF1a receptor (CXCR4), thereby improving migration of CD34+ cells mediated by SDF1a after the 3 month period. Interestingly, in clinical arena our results showed a reduction of pulse wave velocity (an established parameter of arterial stiffness) following CPAP therapy. CONCLUSIONS: Our findings suggest that 3-month CPAP intervention does not show statistical significant increase in CD34+ cell number and function, in mostly moderate to severe OSA subjects; however, it did demonstrate a positive trend. CPAP therapy, did help improve arterial stiffness parameter.

The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.

AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients. METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for < 10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (p < 0.05). RESULTS: Although there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (p < 0.05) and a downregulation in CD34- cells for IL-6 (p < 0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (p < 0.05). CONCLUSION: Saxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477.

The Correlation of Arterial Stiffness with Biophysical Parameters and Blood Biochemistry.

INTRODUCTION: Type 2 diabetes presents with numerous macrovascular and microvascular impairments, which in turn lead to various co-morbidities. Vascular co-morbidities can be seen when examining arterial stiffness (AS), which is a predictor for endothelial health and cardiovascular disease risk. Pulse wave analysis (PWA) and pulse wave velocity (PWV) are two tests that are commonly used to measure AS. Currently, disease states and progression are tracked via blood biochemistry. These gold standards in monitoring diabetes are expensive and need optimization. RESEARCH QUESTION: To investigate which biophysical and biochemical parameters correlated best with AS, which may reduce the number of biochemical tests and biophysical parameter measurements needed to track disease progression. METHODS: Data from 42 subjects with type 2 diabetes mellitus for ≤10 years, aged 40-70 years, were analyzed at a single time point. We investigated various blood biochemistry, body composition, and AS parameters. RESULTS: A combination of fat mass and fat-free mass was most associated with PWA over any other parameters. Leptin and high-sensitivity C-reactive protein seem to be the next two parameters that correlate with augmentation index. No other parameters had strong correlations to either PWA or PWV values. CONCLUSIONS: Body composition methods seemed to be better predictors of type 2 diabetes mellitus patient's vascular disease progression. Our study indicates that body composition measurements may help replace expensive tests. This may have public health and health surveillance implications in countries facing financial challenges.