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BACKGROUND: Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is unclear which endocardial lesions delivered as part of hybrid therapy‚ will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence, then performing tailored endocardial ablation as part of hybrid therapy. METHODS: We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF. RESULTS: Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF ( P =0.017), but had no relationship to reconnection of PVs ( P =0.53) or PW isolation ( P =0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF ( P =0.002), long-standing persistent AF ( P =0.002), advanced age ( P =0.03), and elevated CHA 2 DS 2 -VASc ( P =0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications. CONCLUSIONS: After surgical ablation, AF may recur by several modes particularly related to localized mechanisms near low voltage zones, recovery of posterior wall or pulmonary vein isolation, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.

The optimal methods for measuring and analyzing anal resting and squeeze pressure with high-resolution manometry (HRM) are unclear.Anal resting and squeeze pressures were measured with HRM in 90 healthy women, 35 women with defecatory disorders (DD), and 85 with fecal incontinence (FI). Pressures were analyzed with Manoview™ software and a customized approach. Resting pressures measured for 20, 60, and 300 s were compared. During the squeeze period, (3 maneuvers, 20 s each), the squeeze increment, which was averaged over 5, 10, 15, and 20 s, and squeeze duration were evaluated.Compared to healthy women, the anal resting pressure, squeeze pressure increment, and squeeze duration were lower in FI (p ≤ 0.04) but not in DD. The 20, 60, and 300 s resting pressures were strongly correlated (concordance correlation coefficients = 0.96-0.99) in healthy and DD women. The 5 s squeeze increment was the greatest; 10, 15, and 20 s values were progressively lower (p 0.001). The squeeze pressure increment and duration differed (p 0.01) among the three maneuvers in healthy and DD women but not in FI women. The upper 95th percentile limit for squeeze duration was 19.5 s in controls, 19.9 s in DD, and 19.3 s in FI. Adjusted for age, resting pressure, and squeeze duration, a greater squeeze increment was associated with a lower risk of FI versus health (OR, 0.96; 95% CI, 0.94-0.97).These findings suggest that anal resting and squeeze pressures can be accurately measured over 20 s. In most patients, one squeeze maneuver is probably sufficient.

Context SARS-CoV-2 infects the gastrointestinal tract and may be associated with symptoms that resemble diabetic gastroparesis. Why patients with diabetes who contract COVID-19 are more likely to have severe disease is unknown. Objective We aimed to compare the duodenal mucosal expression of SARS-CoV-2 and inflammation-related genes in diabetes gastroenteropathy (DGE), functional dyspepsia (FD), and healthy controls. Methods Gastrointestinal transit, and duodenal mucosal mRNA expression of selected genes were compared in 21 controls, 39 DGE patients, and 37 FD patients from a tertiary referral center. Pathway analyses were performed. Results Patients had normal, delayed (5 FD [13%] and 13 DGE patients [33%]; P = 0.03 vs controls), or rapid (5 FD [12%] and 5 DGE [12%]) gastric emptying (GE). Compared with control participants, 100 SARS-CoV-2-related genes were increased in DGE (FDR Conclusion Several SARS-CoV-2-related genes were differentially expressed between DGE vs healthy controls and vs FD but not between DGE patients with normal vs delayed GE, suggesting that the differential expression is related to diabetes per se. The upregulation of CTSL and CTSB and replication genes may predispose to SARS-CoV2 infection of the gastrointestinal tract in diabetes.

BACKGROUND AND AIMS: Diagnostic tests for defecatory disorders (DDs) asynchronously measure anorectal pressures and evacuation and show limited agreement; thus, abdominopelvic-rectoanal coordination in normal defecation and DDs is poorly characterized. We aimed to investigate anorectal pressures, anorectal and abdominal motion, and evacuation simultaneously in healthy and constipated women. METHODS: Abdominal wall and anorectal motion, anorectal pressures, and rectal evacuation were measured simultaneously with supine magnetic resonance defecography and anorectal manometry. Evacuators were defined as those who attained at least 25% rectal evacuation. Supervised (logistic regression and random forest algorithm) and unsupervised (k-means cluster) analyses identified abdominal and anorectal variables that predicted evacuation. RESULTS. We evaluated 28 healthy and 26 constipated women (evacuators comprised 19 healthy subjects and 8 patients). Defecation was initiated by abdominal wall expansion that was coordinated with anorectal descent, increased rectal and anal pressure, and then anal relaxation and rectal evacuation. Compared with evacuators, nonevacuators had lower anal diameters during simulated defecation, rectal pressure, anorectal junction descent, and abdominopelvic-rectoanal coordination (P

To review the epidemiology, pathogenesis, clinical features, and management of primary constipation and fecal incontinence in the elderly. Among elderly people, 6.5%, 1.7%, and 1.1% have functional constipation, constipation-predominant IBS, and opioid-induced constipation. In elderly people, the number of colonic enteric neurons and smooth muscle functions is preserved; decreased cholinergic function with unopposed nitrergic relaxation may explain colonic motor dysfunction. Less physical activity or dietary fiber intake and postmenopausal hormonal therapy are risk factors for fecal incontinence in elderly people. Two thirds of patients with fecal incontinence respond to biofeedback therapy. Used in combination, loperamide and biofeedback therapy are more effective than placebo, education, and biofeedback therapy. Vaginal or anal insert devices are another option. In the elderly, constipation and fecal incontinence are common and often distressing symptoms that can often be managed by addressing bowel disturbances. Selected diagnostic tests, prescription medications, and, infrequently, surgical options should be considered when necessary.

Background & objectives: Tumour budding is a feature of epithelial-to-mesenchymal transformation that is characterized histologically within the tumour stroma by the presence of isolated cells or clusters of less than five cells which are different from the other malignant cells. This could be present around the invasive margin of the tumour, called peritumoural budding, or in the bulk of the tumour, called intratumoural budding. The aim of this study was to assess the predictive power of tumour budding for lymph node metastasis and its relationship with other features of tumour progression in colorectal carcinoma (CRC). Methods: Preoperative colonoscopic biopsies and consecutive resection specimens from 80 patients of colorectal cancer were taken. In the biopsy, intratumoural budding was looked for and graded. In the resection, peritumoural budding was seen and graded along with other features such as grade of the tumour, lymphovascular emboli and tumour border configuration. Results: Intratumoural budding was seen in 23 per cent (18/80) and peritumoural in 52 per cent (42/80) of cases. Intratumoural budding was associated with the presence of lymphovascular emboli (P=0.002) and irregular tumour border configuration (P=0.004). Peritumoural budding was also significantly associated with the presence of lymphovascular emboli and irregular margins (P