Colorectal cancer (CRC) is the third most common newly diagnosed cancer in both men and women in the Unites States. Colonoscopy has become increasingly popular in CRC screening and represents the gold standard for detecting and removing pre-cancerous lesions. Although colonoscopy is considered a relatively safe procedure, it is invasive and bowel preparation can be challenging for patients. As interest in the gut microbiome has expanded, there have been new links established between bacteria and the development of CRC. These developing associations could prove to be a useful adjunct to colonoscopy for CRC screening in the future. This review examines current research evaluating multiple proposed pathogenic microorganisms including sulfidogenic bacteria such as , as well as, and . This discussion primarily focuses on bacterial pathogenesis, evidence of association with CRC, and the proposed mechanisms of carcinogenesis.

Background and Aims: NASH is a common disease associated with increased rates of thromboembolism (TE). Although exercise training can lessen thrombotic risk in patients with vascular disease, whether similar findings are observed in patients with NASH is open for study. Approach and Results: We conducted a 20-week randomized controlled clinical trial involving patients with biopsy-confirmed NASH. Patients were randomly assigned (2:1 ratio) to receive either an exercise training program or standard clinical care. The primary endpoint was change in plasminogen activator inhibitor 1 (PAI-1) level, an established thrombotic biomarker. Twentyeight patients were randomly assigned (18 exercise training and 10 standard clinical care). PAI-1 level was significantly decreased by exercise training when compared to standard clinical care (−40 ± 100 vs. +70 ± 63 ng/ml;

Antithrombotic therapy with oral aspirin or clopidogrel (PlavixR) is associated with an attenuated skin vasodilator response and a greater rate of rise in core temperature in healthy, middle-aged individuals during passive heating in a water perfused suit. Purpose The present double-blind, crossover study examined the functional consequences of 7 days of low-dose aspirin (ASA, 81 mg/day) vs. clopidogrel (CLO, 75 mg/day) treatment in 14 healthy, middle-aged (50–65 yrs) men and women during passive heating in air (40 min at 30°C, 40% rh) followed by exercise (60% V̇O2peak). Methods Oral temperature (Tor) was measured in the antechamber (23.0 ± 0.1°C) before entering a warm environmental chamber. After 40 minutes of rest subjects cycled on a recumbent cycle ergometer for up to 120 minutes. Esophageal temperature (Tes) and laser Doppler flux were measured continuously, and the latter was normalized to maximal cutaneous vascular conductance (%CVCmax). Results Prior to entry into the environmental chamber there were no differences in Tor among treatments; however, after 40 minutes of rest in the heat, Tes was significantly higher for ASA and CLO vs. placebo (37.2±0.1°C, 37.3±0.1°C, vs. 37.0±0.1°C, both P<0.001), a difference that persisted throughout exercise (P<0.001 vs. placebo). The mean body temperature thresholds for the onset of cutaneous vasodilation were shifted to the right for both ASA and CLO during exercise (P<0.05). Conclusion ASA and CLO resulted in elevated core temperatures during passive heat stress and shifted the onset of peripheral thermoeffector mechanisms toward higher body temperatures during exercise heat stress.

Background Most patients with nonalcoholic fatty liver disease (NAFLD) are physically inactive despite the well-known benefits of physical activity. Telehealth offers promise as a novel way to deliver an exercise training program and increase physical activity. However, the feasibility, safety, and efficacy of telehealth-based exercise programs is unknown in patients with NAFLD. Objective The aim of this study was to determine the feasibility of a directly supervised exercise training program delivered exclusively with telehealth to patients with nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD. Methods In response to COVID-19 research restrictions, we adapted an existing clinical trial and delivered 20 weeks of moderate-intensity aerobic training 5 days a week under real-time direct supervision using an audio–visual telehealth platform. Aerobic training was completed by walking outdoors or using a home treadmill. Fitness activity trackers with heart rate monitors ensured exercise was completed at the prescribed intensity with real-time feedback from an exercise physiologist. Results Three female patients with biopsy-proven NASH were enrolled with a mean age of 52 (SD 14) years. The mean body mass index was 31.9 (SD 5.1) kg/m2. All patients had metabolic syndrome. All patients completed over 80% of exercise sessions (mean 84% [SD 3%]) and no adverse events occurred. Body weight (mean –5.1% [SD 3.7%]), body fat (mean –4.4% [SD 2.3%]), and waist circumference (mean –1.3 in. [SD 1.6 in.]) all improved with exercise. The mean relative reduction in magnetic resonance imaging-proton density fat fraction (MRI-PDFF) was 35.1% (SD 8.8%). Mean reductions in hemoglobin A1c and Homeostatic Model Assessment for Insulin Resistance were also observed (–0.5% [SD 0.2%] and –4.0 [SD 1.2], respectively). The mean peak oxygen consumption (VO2peak) improved by 9.9 (SD 6.6) mL/kg/min. Conclusions This proof-of-concept study found that supervised exercise training delivered via telehealth is feasible and safe in patients with NASH. Telehealth-based exercise training also appears to be highly efficacious in patients with NASH, but this will need to be confirmed by future large-scale trials. Trial Registration ClinicalTrials.gov NCT03518294; https://clinicaltrials.gov/ct2/show/NCT03518294

Anti-tumor necrosis factor alpha (ATA) therapy plays a significant role in the treatment of moderate to severe inflammatory bowel disease (IBD). There are concerns regarding risks associated with their use, including malignancy and, specifically, lymphoma. Many previous studies have sought to determine whether there is a true link between ATA therapy in IBD and development of lymphoma. However they have been hindered by short follow-up times, few cases, and confounding factors such as previous thiopurine exposure. This review seeks to update the literature by evaluating more recent studies assessing the link between ATA monotherapy and lymphoma development. It also summarizes findings of those studies and provides additional clinical guidance pertaining to this class of biologic therapy.

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Platelet P₂Y₁₂-ADP and COX-1 receptor inhibition with oral clopidogrel (CLO) and low-dose aspirin (ASA), respectively, attenuates reflex-mediated cutaneous vasodilation, but little is known about how these medications affect local vasodilatory signaling. Reactive hyperemia (RH) results in vasodilation that is mediated by sensory nerves and endothelium-derived hyperpolarization factors (EDHF) through large-conductance calcium-activated potassium channels, whereas slow local heating (LH) elicits vasodilation largely through the production of nitric oxide (NO). We hypothesized that CLO and ASA would attenuate locally mediated cutaneous vasodilation assessed by RH and LH (0.5°C/min). In a randomized, cross-over, double-blind placebo-controlled study, nine healthy men and women (56 ± 1 yr) took CLO (75 mg), ASA (81 mg), and placebo for 7 days. Skin blood flow was measured (laser-Doppler flowmetry, LDF) and cutaneous vascular conductance (CVC) was calculated (LDF/mean arterial pressure) and normalized to maximal CVC (%CVCmax: 43°C and 28 mM sodium nitroprusside). RH response parameters, including area under the curve (AUC), total hyperemic response (THR), and the decay constant tau (λ) were calculated. NO-dependent vasodilation during LH was assessed by calculating the difference in %CVCmax between a control site and an NO synthase-inhibited site (10 mM l-NAME: intradermal microdialysis). CLO augmented the AUC and THR (AUCclo = 3,783 ± 342; THRclo = 2,306 ± 266% CVCmax/s) of the RH response compared with ASA (AUCASA = 3,101 ± 325; THRASA = 1,695 ± 197% CVCmax/s) and placebo (AUCPlacebo = 3,000 ± 283; THRPlacebo = 1,675 ± 170% CVCmax/s; all P < 0.0001 vs. CLO). There was no difference in the LH response or calculated NO-dependent vasodilation among treatments (all P> 0.05). Oral CLO treatment augments vasodilation during RH but not LH, suggesting that CLO may improve cutaneous microvascular function.