Verastegui, Alfredo

Abstract Purpose To evaluate the association of long-term, continuous tirzepatide use with cardiometabolic risk parameters and estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk in real-world practice. Methods This multicenter retrospective observational study included 1,028 adults with overweight or obesity who received weekly subcutaneous tirzepatide for at least 12 months within the Mayo Clinic Health System from June 2022 through May 2024. ASCVD risk analyses included 275 individuals with complete baseline and 12-month follow-up data. Outcomes were changes in cardiometabolic parameters, estimated 10-year ASCVD risk, and ASCVD risk category. Results At 12 months, median total body weight loss (TBWL) was 12.6%. Fasting glucose, HbA1c, triglycerides, and alanine aminotransferase decreased by 19.5%, 16.0%, 8.5%, and 10.6%, respectively, whereas HDL cholesterol increased by 11.3% (all P < .001). Mean 10-year ASCVD risk did not change significantly overall (mean relative change, −3.7%; P = .18), but changes differed by TBWL category (ANOVA, P < .001). ASCVD risk decreased among individuals achieving 10%–20% TBWL (−9.6%; P = .009) and >20% TBWL (−14.2%; P = .005), but not among those achieving <10% TBWL (+7.7%; P = .22). Low-risk prevalence increased from 38.3% to 46.4% (P < .001), with 11.7% transitioning from higher-risk categories to low risk. Main findings Continuous tirzepatide use for at least 12 months was associated with clinically meaningful improvements in cardiometabolic parameters. Reductions in estimated 10-year ASCVD risk were observed among individuals achieving at least 10% TBWL, supporting greater weight loss as an important marker of cardiovascular risk improvement.

ABSTRACT Objective This study assessed the impact of sex and age on weight loss outcomes in patients receiving tirzepatide in real‐world clinical practice. Methods We conducted a retrospective cohort study of adults with overweight or obesity who initiated tirzepatide at Mayo Clinic between June 2022 and May 2024 and completed ≥ 12 months of continuous therapy. Primary outcome was total body weight loss percentage (TBWL%) at 15 months, stratified by sex and age groups (≤ 45, 46–59, ≥ 60 years). Results Among 1039 patients (57% women; mean age 56 ± 11 years), women achieved significantly greater TBWL% than men after 15 months of treatment (15.1% vs. 10.7%, p < 0.001). Patients aged ≤ 45 years had greater weight loss than those ≥ 60 years (15.1% vs. 12.3%, p = 0.024). In multivariable analyses, greater weight loss was independently associated with female sex, absence of type 2 diabetes, no prior obesity medication use, no concomitant weight gain‐promoting medications, and higher tirzepatide dosage. Age was not an independent predictor. Conclusions Sex, but not age, predicted weight loss with tirzepatide among individuals using the medication continuously for ≥ 12 months. These findings underscore the importance of incorporating sex‐specific considerations into personalized obesity treatment strategies.

Abstract Introduction Revascularization to prevent limb loss is not feasible or represents a very high risk in a significant proportion of patients with chronic limb-threatening ischaemia (CLTI). No standard definition currently exists to define this population of patients. The aim of this study was to develop a consensus-based, multidomain definition to improve clinical assessment and reporting of studies in people with ‘no option’ (NO) or ‘poor option’ (PO) CLTI. Methods A modified Delphi process was conducted with 164 specialists from 30 countries. Two iterative survey rounds were used to reach consensus, defined as ≥70% agreement with a score of ≥7 on a nine-point scale. Results Some 164 international vascular specialists participated in the study, averaging 19 years of experience. A multidomain framework including arterial disease anatomy, biology, risk, function, and context (ABRFC) achieved 83% consensus. A ‘desert foot’ was defined as the absence of distal arterial revascularization targets on advanced non-invasive imaging, invasive digital subtraction angiography, and at least one failed endovascular revascularization attempt (81.6% agreement). Inadequate autogenous bypass conduit was defined as the lack of usable autologous vein across all four limbs (85% agreement). Patients were classified as NO for revascularization if they present with ‘desert foot’, prohibitive medical risk, a non-functional limb, or in those patients who refused arterial revascularization. PO revascularization patients combined factors such as severe infection, lack of autologous vein, or treatment non-compliance (72.1% agreement). Conclusion This consensus study established a structured, expert-validated definition of no option or poor option for revascularisation of patients with CLTI. The multidomain ABRFC framework provides a foundation for standardized clinical assessment, trial design, and future guideline development.

Background/Objectives: Individuals with type 2 diabetes (T2D) achieve less total body weight loss (TBWL) with obesity medications compared to those without T2D. The individualized metabolic surgery (IMS) score, originally developed to predict T2D remission after bariatric surgery, inversely correlates with TBWL response to semaglutide. IMS reflects T2D severity, incorporating HbA1c and T2D duration and medication use. This study aims to evaluate TBWL with tirzepatide across IMS severity categories and identify predictors of response in a real-world cohort. Methods: This retrospective analysis included 717 adults with T2D using tirzepatide for overweight or obesity within the Mayo Clinic Health System. Patients were stratified by IMS severity (mild, moderate, severe) and quartiles. Primary endpoint: TBWL% at 15 months. Secondary endpoints: categorical thresholds (≥5%, ≥10%, ≥15%, ≥20%) and predictors of TBWL%. Linear mixed-effects models and regression models were employed. Results: At 15 months, TBWL was greater in mild versus severe IMS groups (14.8% vs. 11.0%, p = 0.015), with similar trends across quartiles. The proportion achieving ≥ 20% TBWL was nearly two-fold higher in mild versus severe IMS (27% vs. 14%, p = 0.03). Female sex independently predicted greater TBWL, whereas insulin use, higher T2D medication burden (particularly weight-promoting agents), and HbA1c > 7% were associated with less TBWL. Conclusions: Tirzepatide produced clinically meaningful TBWL across all IMS categories, although TBWL declined with increasing IMS severity. Glycemic control and T2D medication use emerged as strong predictors of TBWL. The IMS score may serve as a practical tool to anticipate weight-loss trajectories, guide personalized treatment decisions, and inform patient counseling.

Background: Peripheral artery disease (PAD) is a global health challenge. Advances in artificial intelligence (AI), such as large language models (LLMs) and chain-of-thought (CoT) reasoning, offer novel approaches for clinical recommendations. This study compared the readability and guideline adherence of responses from physicians and AI for a standardized PAD case. Methods: This cross-sectional study gathered responses from 30 specialized physicians (11 cardiologists, 19 vascular surgeons) across seven Latin American countries and 13 LLM systems (10 standard, three CoT). Both groups addressed diagnosis, treatment, risks, and prognosis; LLMs responded as vascular specialists. Responses were blindly evaluated with five validated Spanish readability indices and compared to the 2024 ACC/AHA multisocietal PAD guideline. Three experts scored guideline adherence; nonparametric tests were applied. Results: Guideline adherence did not differ significantly between physicians (median 5.8 [3.4–7.6]) and LLMs (7.3 [4.7–9.7], p = 0.169), though CoT-LLMs achieved the highest scores (9.7 [8.5–11.0]). LLMs more often recommended supervised exercise (84.6% vs 30.0%, p = 0.002) and revascularization for quality of life (69.2% vs 20.0%, p = 0.004), whereas physicians favored cilostazol (60.0% vs 30.8%, p = 0.104). LLM responses had lower Readability μ values (46.9 vs 51.4, p = 0.012). Inter-rater reliability was highest for CoT-LLMs (intraclass correlation coefficient [ICC] = 0.98) versus physicians (ICC = 0.76). Conclusion: LLM showed comparable guideline adherence to physicians although CoT models achieved the highest scores. The difference in physician and AI treatment preferences suggest the potential of AI as adjunct clinical tools and warrants further study.

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation.

Introduction Due to rising incidence of Hepato-Pancreato-Biliary (HPB) malignancies and more effective therapies, there are increased survivors after curative surgery but little emphasis is placed on survivorship. This study aims to evaluate the value and yield of postoperative surveillance of surgically treated HPB cancer patients within a single surgeon’s practice. Methods A retrospective 1-year (2024) review identified 128 unique patients with prior surgical resection of a HPB malignancy undergoing active cancer surveillance by the surgical team. We excluded patients with benign indications for surgery or active cancer surveillance outside of the surgical team. Results Of these, 112 (87.5%) and 16 (12.5%) underwent pancreatic and hepatobiliary resection, respectively. Median follow up was 1.5 years from the index operation (IQR: 0.7-2.8 years). Pancreatic pathology was pancreatic adenocarcinoma (PDAC), neuroendocrine, or miscellaneous in 70, 25, and 9 patients, respectively. Hepatobiliary pathology was cholangiocarcinoma (CCA), metastatic colorectal cancer, or hepatocellular carcinoma in 16, 6, and 2 patients, respectively. We identified 12 (9.3%) patients who had findings during the study time period resulting in a repeat HPB surgery. In addition, we identified 12 (9.3%) patients who required referral to another department for additional medical, surgical, or interventional treatments. The remaining 104 (81.2%) patients had findings of either no disease recurrence or stable disease with continued surveillance as a recommendation. Conclusion This study underscores the value of cancer surveillance for HPB cancer patients, demonstrating a yield of nearly 20% of patients with findings requiring repeat surgical intervention or referral to other departments.

Background Whistal (Whipple + Distal) is a rare parenchyma-preserving technique for select patients with disease in both the pancreatic head and tail, sparing a disease-free middle segment. It may also be used after prior partial pancreatectomy. Surgical resection remains the cornerstone of treatment for pancreatic diseases such as PDAC, RCC metastasis, and multifocal IPMN. Whistal may balance oncologic control with pancreatic function preservation. Though infrequent, it is practiced and reported in literature. Methods With IRB approval, a retrospective review of a prospective database (Aug 1999-Mar 2024) identified Whistal cases, categorized as staged Whistal (SW) or concomitant whistal (CW). Perioperative outcomes were assessed via Clavien-Dindo and ISGPS. A PubMed search identified reported middle segment pancreatectomy (Whistal) cases. Results Of 2008 resections (Aug 1999-Mar 2024), 5 were Whistals (3 CW, 2 SW) for PDAC (n = 3), RCC (n = 1), IPMN (n = 1), and bile duct stricture (n = 1). Rates for major morbidity, POPF, and DGE were each 40%. Literature review found 26 papers reporting 52 additional Whistal cases. Conclusion Whistal is safe for select patients, but wider adoption and long-term data are needed to confirm its efficacy.

Background: Despite advances in surgical techniques and perioperative care, pancreatic resections such as pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) remain high-risk procedures. Postoperative complications significantly impact morbidity, mortality, and patient quality of life. Methods: This narrative review summarizes recent literature on major complications following pancreatic surgery, including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), and post-pancreatectomy hemorrhage (PPH), with an emphasis on incidence, risk factors, outcomes, and current preventive strategies. Results: POPF is a leading complication, occurring in 5–22% of cases and often linked with sepsis and hemorrhage. Key risk factors include high BMI, soft pancreatic texture, and small duct size. Preventive measures like Pasireotide, modified anastomosis techniques, and neoadjuvant therapy show variable success. DGE affects up to 57% of PD patients and is associated with prolonged recovery; antecolic reconstruction and erythromycin may reduce incidence. PPH, though less frequent (3–13%), can be life-threatening, particularly when secondary to POPF. Endovascular approaches are now favored for late arterial bleeding. Other complications include wound infections, abscesses, bile leaks, and pulmonary issues, all contributing to extended hospital stays and diminished quality of life. Conclusions: Pancreatic surgery continues to carry significant risks, with POPF, DGE, and PPH being the most impactful complications. While multiple interventions have shown promise, standardized protocols and predictive tools are still needed. Surgery should be performed in high-volume centers with experienced multidisciplinary teams to optimize outcomes.

Background Pancreatoduodenectomy (PD) is the only curative treatment for pancreatic cancer. Neoadjuvant therapy (NAT) has enhanced survival, especially for downstaging advanced tumors, while also introducing complexities and new complications. Despite surgical advances, some PD attempts remain unsuccessful. The management of these cases is not well defined. This study analyzes outcomes of repeat PD performed by two high-volume surgeons following previously unsuccessful attempts. Methods We retrospectively analyzed patients with pancreatic neoplasm undergoing successful pancreaticoduodenectomy (2013-2024) at two high-volume centers under two experienced surgeons. Only cases with prior aborted PD attempts for non-metastatic disease were included. Data from institutional records provided outcomes on failure reasons, procedure timing, surgical details, and 90-day complications. Results Of the 858 PD cases, 18 patients (2.1%; 12 males, 6 females; median age 69 years) had prior unsuccessful PD attempts at other institutions. Initial tumors were borderline resectable (33.3%), resectable (22.2%), or locally advanced (22.2%). Main causes for initial failure were vascular involvement (41.2%) and tumor infiltration (17.6%). Median time between attempts was 246 days, with 77.8% receiving chemotherapy before the second attempt. The second procedure achieved R0 resection in 94.4% of cases. Major 90-day complications occurred in 23.5% of patients, with no perioperative mortality. Disease recurrence occurred in 38.9% within the first year. Conclusion Repeat PD after an aborted attempt is feasible in select patients at specialized centers. However, complication and recurrence rates emphasize the need for careful patient selection. Further research is needed to optimize management strategies.