Citations

Abstract Background Minimally invasive colorectal surgery is characterized by significant procedural variability, a difficult learning curve, and complications that affect patient outcomes. Video-based assessment offers an opportunity to generate data-driven insights to reduce variability, optimize training, and improve surgical performance. This mixed-methods study aimed to develop and validate a video-based assessment tool for workflow analysis across minimally invasive colorectal procedures. Methods An international steering committee panel of seven members coordinated a three-round modified Delphi process. Experts in colorectal surgery and video-based assessment were invited to reach consensus (≥ 70% agreement) on the phases and steps that describe workflows across colorectal surgery procedural videos. The resulting framework informed the development of ColoWorkflow. Four independent raters then applied ColoWorkflow to a multicentre video data set of laparoscopic and robotic colorectal procedures. Applicability and inter-rater reliability were evaluated. Results Of 66 invited experts, 41 (62%) from 11 countries completed round 1, 40 (98%) completed round 2, 20 attended the final online consensus meeting, and all (40 of 40) approved the final workflow descriptors. Consensus was achieved on nine procedure-agnostic phases (port placement and abdomen exploration; vascular dissection and ligation, mesocolon/mesorectum dissection, additional lymphadenectomy; colon and/or rectum mobilization; colorectal transection; anastomosis; completion of operation; preplanned additional procedures; unplanned procedures; extracorporeal procedures) and 34 procedure-specific steps that describe colorectal surgery workflows. ColoWorkflow was developed and applied to 54 colorectal surgery videos (left and right hemicolectomies, sigmoid and rectosigmoid resections, and total proctocolectomies) from five centres in four countries. The tool demonstrated broad applicability, as all phase and step labels, except one, were represented in at least one video. Inter-rater reliability was moderate, with a mean Cohen’s κ value of 0.72 for phases and 0.67 for steps. Most discrepancies arose at phase transitions and step boundary definitions. Conclusion Based on this preliminary work, ColoWorkflow is a promising tool for workflow analysis across minimally invasive colorectal procedures. Its adoption may help standardize training, accelerate competency acquisition, and advance data-informed surgical quality improvement.

Abstract Optimal management of anticoagulation for patients with aortic mechanical heart valves (MHVs) receiving vitamin K antagonists (VKAs) undergoing gastrointestinal endoscopic procedures is clinically challenging. Risk of bleeding from an unanticipated polypectomy or biopsy further complicates this issue. Current guidelines on use of bridging with low-molecular-weight heparin (LMWH) for these procedures are based on low-quality evidence. We conducted a subanalysis of a retrospective, multicenter observational study of adult patients with aortic MHVs receiving VKAs who underwent elective gastrointestinal endoscopies (colonoscopy or upper endoscopy). We included patients who underwent the procedure between July 1, 2020, and July 1, 2023, at five centers in Canada and the United States Patients with procedures performed on separate days within a 30-day period were excluded. Efficacy and safety outcomes included thromboembolic events, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) in the 30 days post procedure. A total of 192 endoscopic procedures were analyzed. Median (interquartile range [IQR]) patient age was 66 years (58.2–72.8) and 22% were female. Warfarin was interrupted for 185 procedures (96%). Among these, 119 (64%) received LMWH bridging: 33 (17%) pre-procedure only, 10 (5%) post-procedure only, and 76 (40%) both pre- and post-procedure. Post-procedure LMWH was initiated a median (IQR) of 1 day (1–1) and discontinued 5 days post-procedure (3–8). MB occurred in two patients (1%), CRNMB in two patients (1%), and one death (0.5%) was identified; no thromboembolic events occurred. Prior to propensity score matching (PSM), post-procedure LMWH with or without pre procedure LMWH was associated with the composite outcome of MB and CRNMB (P = 0.034), although not with MB or CRNMB individually. After stepwise regression and PSM analyses, no significant differences in bleeding outcomes were observed between patients who received LMWH bridging and those who did not. Our findings indicate that although adverse thrombotic events were rare and use of post-procedure LMWH bridging was significantly associated with a small absolute increased risk of bleeding, it was not significant after PSM. Larger prospective studies are needed to better inform antithrombotic management guidelines for patients with aortic MHVs undergoing gastrointestinal endoscopy.

Hypertension is the main risk factor for cardiovascular disease (CVD), affecting 20–40% of Latin American (LATAM) adults, and responsible for more than two million deaths annually due to CVD. The different ethnic, economic, geographic, and cultural characteristics of the LATAM population influence the high prevalence of all cardiovascular risk factors (CVRF), particularly metabolic disturbances such as type 2 diabetes (DM2), obesity and the metabolic syndrome. Their main determinants in LATAM includes environment, food quality, social inequity, low education, political aspects, contextual behaviour, and genetics. The prevalence of overweight and obesity in LATAM increased during the last four decades reaching figures of 10–20% in childhood, 30–40% in adolescence, and 60–70% in adults. Many studies in the region have reported the extremely low rates of awareness, treatment, and control of CVRF in the general population of LATAM, particularly in patients with metabolic disorders, and the consequent high cardiovascular morbidity and mortality. This 2026 LATAM consensus is developed by a large group of experts from different LATAM countries, the USA and Europe, representing areas of internal medicine, cardiology, nephrology, endocrinology, geriatrics, paediatrics, pharmacology, and epidemiology. A careful search for novel studies in LATAM, together with new evidence that has emerged since the 2019 LATAM consensus, support the statements and recommendations in the current report. This update aims to provide clear and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated CVRF in the region.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), with acute interstitial nephritis (ICI-AIN) being the most common irAE. While the exact mechanism remains unclear, upregulation of IFN-γ and TNF-α pathways has been implicated. This study used a humanized chimeric PD-1/PD-L1 mouse model to assess renal effects of ICIs, alone or combined with proinflammatory cytokines, and to test if selective TNF-α blockade could prevent ICI-AIN. Mice were randomly divided into 4 experimental groups: Control, ICI-Only, ICI-Cytokines (ICI-Cyt), and ICI-Block (ICI-TNF-α blockade). Renal function and cytokine profiles were assessed, while kidney tissue was analyzed using microscopy and single-cell RNA-seq. Histology revealed increased renal infiltration of CD4 + /CD8 + T cells in ICI-treated groups and decreased TNF-α expression following TNF-α blockade. Additionally, kidney tissue ELISA demonstrated reduced IFN-γ levels following TNF-α blockade. Plasma IL-6, MCP-1, and TNF-α were lower in ICI-Block mice. Single-cell RNA-seq revealed shifts in immune cell populations and genes of interest including Bcl2a1 , Icos , Il18r1 , Ccr2 , and Jaml . This humanized model replicates ICI-AIN key features, revealing a synergistic role of ICIs and proinflammatory cytokines. TNF-α blockade demonstrated protective effects, supporting its potential role in mitigating the risk of ICI-AIN.

LBA630 Background: Enfortumab vedotin (EV) + pembrolizumab (pembro) is the established first-line standard of care for locally advanced/metastatic urothelial carcinoma and represents a novel neoadjuvant and adjuvant treatment strategy for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy. The randomized phase 3 KEYNOTE-B15/EV-304 study (NCT04700124) evaluates neoadjuvant and adjuvant EV + pembro followed by radical cystectomy plus pelvic lymph node dissection (RC + PLND) vs neoadjuvant chemotherapy followed by RC + PLND in participants (pts) with MIBC who are eligible for cisplatin-based therapy. Methods: Pts with clinical stage T2-T4aN0M0 or T1-T4aN1M0 MIBC (confirmed by central pathology and central imaging assessment) who were eligible for cisplatin-based chemotherapy and RC + PLND were randomized 1:1 to receive either 4 cycles neoadjuvant EV 1.25 mg/kg IV on days 1 and 8 + pembro 200 mg IV on day 1 Q3W, followed by RC + PLND, and adjuvant 5 cycles EV + 13 cycles pembro (EV + pembro arm) vs 4 cycles neoadjuvant gemcitabine 1000 mg/m 2 on days 1 and 8 + cisplatin 70 mg/m 2 on day 1 Q3W, followed by RC + PLND (cis + gem arm). The primary endpoint was event-free survival (EFS) by blinded independent central review. Key secondary endpoints were pathological complete response (pCR) rate by blinded central pathological review and overall survival (OS). Safety was a secondary endpoint; AEs of special interest were based on distinct prespecified lists for each drug. Results: A total of 405 and 403 pts were randomized to EV + pembro and cis + gem, respectively. Median time from randomization to the data cutoff date of October 27, 2025 was 33.6 months (range, 22.5–53.6). Baseline characteristics were generally balanced between groups. EV + pembro significantly improved EFS (median NR vs 48.5 mo; 24-mo estimated EFS rate 79.4% vs 66.2%; HR 0.53, 95% CI 0.41–0.70; 1-sided P <.0001), OS (median NR vs NR; 24-mo estimated OS rate 86.9% vs 81.3%; HR 0.65, 95% CI 0.48–0.89; 1-sided P =.0029), and pCR rate (55.8% vs 32.5%; estimated difference 23.4%, 95% CI 16.7–29.8; 1-sided P <.0001) vs cis + gem. Grade ≥3 treatment-emergent AEs occurred in 75.7% of pts with EV + pembro and 67.2% with cis + gem. Most common grade ≥3 drug-related AE of special interest for EV was skin reactions (14.1%); most common grade ≥3 AE of special interest for pembro was severe skin reactions (13.9%). Conclusions: Neoadjuvant and adjuvant EV + pembro significantly improved EFS, OS, and pCR rate compared with neoadjuvant gem + cis in pts with MIBC who were eligible for cisplatin-based chemotherapy. The safety profile of EV + pembro was consistent with prior experience with the combination. These results support EV + pembro as an effective perioperative treatment option in this setting. Clinical trial information: NCT04700124 .

PURPOSE BRCA carriers face high risks of developing both breast and ovarian/fallopian tube cancers (hereafter referred to as ovarian ). Among BRCA carriers with ovarian cancer, it is not clear whether the risk of breast cancer is sufficiently high that risk-reducing mastectomy should be offered. This study aimed to assess the risk of breast cancer BRCA carriers after a diagnosis of ovarian cancer. METHODS We included women with a pathogenic/likely pathogenic variant in BRCA1 or BRCA2 , a diagnosis of ovarian cancer, and no other cancer history and no risk-reducing bilateral mastectomy. Women were followed for incident breast cancer from the date of ovarian cancer diagnosis or the date of baseline questionnaire, whichever came last. The 5-, 10-, and 15-year cumulative risks of breast cancer were compared for women with ovarian cancer and an age-matched set of control women without ovarian cancer. RESULTS A total of 960 participants with ovarian cancer were identified (814 BRCA1 and 146 BRCA2 carriers). After a mean follow-up of 4.9 years, 41 women (4.3%) developed breast cancer, at a mean age at diagnosis of 57.5 years (range, 39-74). Actuarial cumulative breast cancer risks after ovarian cancer were 4.4%, 8.9%, and 11.5% at 5, 10, and 15 years, respectively. Only three breast cancer–related deaths occurred. Among 741 age-matched BRCA carriers without ovarian cancer, actuarial cumulative risks of breast cancer were 20.9%, 38.6%, and 47.2% at 5, 10, and 15 years, respectively. The hazard ratio for breast cancer, after an ovarian cancer diagnosis, compared with no ovarian cancer, was 0.18 ([95% CI, 0.12 to 0.27]; P < .0001). CONCLUSION After ovarian cancer, BRCA carriers have a relatively low risk of breast cancer. Risk-reducing mastectomy should not be recommended routinely, but might be considered for long-term survivors. Magnetic resonance imaging surveillance and/or mammography is a realistic alternative.

We provide the first longitudinal and most comprehensive analysis of the intrarenal microvasculature in a slowly progressive model of autosomal dominant polycystic kidney disease (ADPKD) and integrate the findings with studies in a young cohort of individuals with ADPKD. We identified vasculature-related pathways that could be targeted for therapeutic interventions and contribute promising, noninvasive biomarkers in patients with ADPKD. Alterations of the intrarenal microcirculation may affect drug delivery; a better understanding of its longitudinal changes may aid in treatment management.

Abstract Background Exercise stress echocardiography (ESE) is recommended in patients with mitral regurgitation (MR) when resting echocardiographic findings and symptoms do not align. However, the role of MR assessment in patients undergoing ESE for any indication remains uncertain. Purpose This study aimed to investigate whether the assessment of MR during ESE provides prognostic value beyond the evaluation of inducible regional wall motion abnormalities (RWMA) in patients undergoing ESE for any clinical indication, including suspected coronary artery disease (CAD). Methods Data were analyzed from a large multicenter and multinational prospective study. Current analysis included patients who underwent ESE for any indication and had MR (from 0= absent, to 3= severe) assessed at rest and peak exercise with an integrated qualitative, semi-quantitative, and (in selected cases) quantitative assessment. The primary endpoint was all-cause mortality. Results Of 1,351 included patients (age 56±16 years; 66% women; 30% with known CAD). MR score increased during exercise (rest=0.74±0.7 vs. peak=0.89±0.8, p&lt;0.001), with severe MR present in 2% of patients at rest and 7% at peak ESE. Patients with severe MR during exercise (n=96, Group 1) compared to those with non-severe MR during exercise (n=1255, Group 2) showed more B-lines, lower left ventricular contractile and chronotropic reserve, and trend (p=0.09) to more frequent decrease in ejection fraction during ESE (Table 1). After a median follow-up of 2.1 years (IQR 1.0–6.9), 99 patients (7%) had died. Severe MR at rest was associated with increased mortality (log-rank p&lt;0.001). Patients with severe MR at peak ESE had a higher risk of death compared to the other patients (log-rank p 0.035) (Figure 1). After adjusting for age, CAD, and inducible RWMA, severe MR with exercise remained strongly associated with an increased risk of death (adjusted-HR: 2.2, 95%CI 1.3-3.8, p=0.002). Similar results were seen with further adjustment for rest MR severity (adjusted-HR:1.9, 95%CI 1.02-3.5, p=0.004). Conclusion Patients, with and without CAD, with severe MR during ESE have greater functional impairment expressed by more pulmonary congestion, blunted heart rate reserve, and lower left ventricular contractile reserve. The assessment of MR during ESE provides significant prognostic information, independent of resting RWMA or inducible ischemia. Incorporating MR evaluation into routine ESE protocols may improve clinical decision-making and patient outcomes.Fig 1 Survival by MR at peak exercise Table 1

Abstract Background The functional significance of the left ventricular (LV) hypercontractile phenotype (HP) in hypertrophic cardiomyopathy (HCM) remains unclear. Purpose To assess the systemic and coronary hemodynamic correlates of HP in HCM. Methods We enrolled 1533 HCM patients (age 51 ± 15 years, 965 males, 63%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 27 laboratories from 13 countries. Two-dimensional volumetric TTE assessment included LV outflow tract gradient (LVOTG), end-diastolic volume (EDV), end-systolic volume (ESV), EF, and LV force (systolic blood pressure + LVOTG/ESV, mmHg/mL). Coronary flow velocity in the mid-distal left anterior descending (LAD) coronary artery was assessed in 325 patients. HP was defined as the highest quartile of the force (&gt; 7.32 mmHg/ml). Results Force was moderately related to EF (r = 0.48, p &lt; 0.0001) and weakly to LVOTG (r = 0.36, p &lt; 0.0001). Compared to non-HP patients, HP showed higher heart rate (72 ± 14 vs 67 ± 14 beats per minute, p &lt;0.0001), lower stroke volume (50 ± 22 vs 67 ± 22 ml, p &lt; 0.0001), larger left atrial volume index (44 ± 16 vs 40 ± 16 ml/m2, p = 0.011) and higher coronary flow velocity in the LAD (n = 325, 41 ± 12 vs 37 ± 14 cm/s, p = 0.021), see Figure. Abnormal B-lines (≥ 2) were present in 11 of the 39 HP compared to 39 of the 271 non-HP patients (28% vs 14 %, p = 0.05). E/e’ ratio was higher in HP (n = 59) vs. non-HP (n = 571) patients (11 ± 5.4 vs 9.6 ± 4.2, p = 0.018). Conclusion In patients with HCM, preserved EF, and no history of coronary artery disease, HP identified by resting TTE with supernormal LV force was associated with an unfavorable systemic hemodynamic and coronary flow profile. Compared to non-HP HCM patients, the HP was characterized by reduced stroke volume, impaired diastolic function, and increased resting coronary flow velocity. HP may reflect inefficient myocardial mechanics, with disproportionate energy expenditure mirrored by higher resting coronary flow despite reduced stroke volume generation, ultimately contributing to adverse remodeling and worse prognosisNon-HP vs HP LAVI and coronary LAD flow