Toronto General Hospital

To provide recommendations for the most appropriate endovascular intervention of femoropopliteal (FP) arterial disease based on plaque characterization. A panel of 22 physicians from multiple disciplines participated in a modified Delphi consensus, leveraging the RAND/UCLA Appropriateness Method. Panelists engaged in 2 rounds of voting, following a literature review, with an in-person discussion prior to the second round of voting. A rigorous statistical approach was used to analyze the points of agreement and disagreement. Consensus-based recommendations on the most appropriate endovascular approaches for treating patients with FP lesions, stratified by lesion morphology, were generated. Overall, 490 individual items were included in the voting, 458 (93%) of which achieved consensus and 32 (7%) were nonconsensus items, based on a priori criteria under the following categories: (a) recommendations on method for determining plaque morphology, (b) preferred endovascular devices for vessel preparation and definitive treatment stratified by (i) plaque morphology and (ii) Tosaka classification of in-stent restenosis, and (c) vessel preparation device safety-related considerations. This international, multidisciplinary consensus provides evidence- and expert-informed recommendations for vessel preparation and definitive treatment of FP arterial disease, tailored to plaque morphology. These consensus recommendations aim to support clinical decision making and promote best interventional practices by serving as an expert opinion supplement to existing guideline-based care pathways.

Statins, used for cardiovascular disease (CVD) prevention, may offer hepatoprotective benefits. However, adherence to treatment indications and the associations between statin use, metabolic dysfunction-associated steatotic liver disease (MASLD), and elevated liver stiffness in the general population remain poorly understood. This prospective, population-based study included adults aged ≥40 years between 2011 and 2020. We evaluated statin indications for CVD risk using prevailing European Society of Cardiology/European Atherosclerosis Society clinical practice guidelines based on SCORE2 and SCORE2-Older Persons algorithms. We used multivariable regression to examine associations between statins, MASLD, and elevated liver stiffness, adjusting for demographic, socioeconomic and metabolic covariables. We performed dose-response analyses using WHO defined daily dosages. Of 6,405 eligible individuals, 6,055 participants were included in the analysis (median age 64 years; 56% female); MASLD was present in 32%, elevated liver stiffness in 4.8%, and statin use in 21%. Participants with MASLD had higher predicted 10-year CVD risk compared to participants without MASLD (p <0.001), yet were less likely to use statins: 33% of individuals with MASLD and an indication for statin treatment remained untreated, compared to 19% of those without MASLD (p <0.001). Statin use was associated with lower prevalence of MASLD (adjusted odds ratio 0.76; 95% CI 0.63-0.92) and elevated liver stiffness (adjusted odds ratio 0.65; 95% CI 0.46-0.92) relative to untreated individuals with a statin treatment indication. The highest statin WHO defined daily dosage category was associated with lower prevalence of MASLD (p = 0.033) and elevated liver stiffness (p = 0.035). Individuals with MASLD are less likely to use statins despite a contemporary guideline-based indication. Statin use is independently associated with lower prevalence of both MASLD and elevated liver stiffness. These findings underscore the need to improve CVD risk management in this population with the potential added benefit of mitigating MASLD. In this large prospective, population-based study, statins were underutilized in metabolic dysfunction-associated steatotic liver disease (MASLD) compared to non-MASLD individuals, even though they had the highest cardiovascular risk and met guideline-based treatment criteria. Our findings further demonstrate that individuals who used statins had a lower likelihood of MASLD and elevated liver stiffness compared with statin-eligible individuals who were not treated. Taken together, these results highlight a missed opportunity: optimizing statin use in people with MASLD could strengthen cardiovascular disease prevention while also offering potential benefits for liver health.

Abstract Background Postoperative delirium is a common complication in surgical patients, and is associated with a multitude of negative outcomes, including mortality, dementia, and increased healthcare costs. Therefore, a better understanding of what factors contribute to postoperative delirium, especially those that can be easily obtained, is important. Methods We conducted a retrospective cohort study using patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Adult patients undergoing procedures in abdominal surgery who did not have pre-existing delirium were included in the study. Overall, we included 8022 procedures across 7212 patients. For each admission, we extracted values obtained from common blood tests, the Charlson and Elixhauser comorbidity score, and patient demographic information. We used stepwise logistic regression to identify predictive factors of postoperative delirium in this cohort. Results The model isolated factors well known to be associated with postoperative delirium, such as age, comorbidity (as represented by the Elixhauser comorbidity score), and Parkinson’s disease. The model also selected variables that are less studied, such as minimum preoperative platelets and maximum preoperative sodium levels. We hypothesize that the former is associated with postoperative delirium as a surrogate marker for inflammation as an acute phase reactant, and the second due to it being a marker for cerebral edema and altered neurotransmission. Conclusion Preoperative blood tests contain valuable information that can be used alongside patient demographics and past medical history to better predict the risk of postoperative delirium.

Preserving health and quality of life are priorities of care for living liver donors (LLDs) due to their altruistic contribution to recipients. No study has examined the role of multimodal prehabilitation for living donor liver transplantation (LDLT). Prior to determining the efficacy of prehabilitation in LLDs, a feasibility study is required. The objective of this feasibility randomized controlled trial (RCT) was to assess the feasibility of conducting a large-scale RCT of prehabilitation prior to LDLT. Thirty LLDs at Toronto General Hospital were randomized 2:1 to receive multimodal prehabilitation or usual care, respectively. The prehabilitation intervention comprised: (1) exercise, (2) nutrition support, (3) psychological counselling, and (4) LLD peer mentor sessions. The primary outcome was feasibility via rates of recruitment, retention, adverse events, adherence, and healthcare provider engagement. Clinical, patient-reported, and physical fitness outcomes were collected at baseline, preoperatively, and at 4 and 12 weeks postoperatively. Qualitative interviews were used to assess feasibility and satisfaction with the intervention. Sixty-three patients were eligible and 30 enrolled (48%). Participants' mean age was 42 ± 8 and 67% were female. There were no intervention-related adverse events. Attrition was 33% and adherence across each of the components of prehabilitation was ≥75%. Interviews demonstrated satisfaction with the prehabilitation intervention and areas for improvement for a Phase III RCT. This study demonstrates a Phase III RCT of prehabilitation versus usual care may be feasible in LLDs. The Phase III trial will confirm the preliminary and exploratory physical and psychosocial benefit reported in this study. ClinicalTrials.gov identifier: NCT0543136.

Introduction: Cardiogenic shock (CS) is a life-threatening syndrome of cardiac pump failure. In this setting, inadequate renin-angiotensin-aldosterone system (RAAS) activity may contribute to impaired organ perfusion. Angiotensin-converting enzyme 2 (ACE2) counter-regulates RAAS by degrading angiotensin II into vasodilatory peptides and thus, may exacerbate hypoperfusion in CS. To date, soluble ACE2 (sACE2) activity has not been characterized in this population. This study compared sACE2 activity between patients with CS and stable heart failure (sHF) and investigates its association with mortality. Methods: Plasma samples were obtained from 339 CS patients within 24 hours of admission to the Toronto General Hospital between January 2014 and December 2020 and from 343 sHF patients, matched for age, sex, ejection fraction, and HF etiology. sACE2 enzymatic activity was measured using a fluorometric assay. Fine–Gray subdistribution hazard models were used to assess the association between sACE2 and mortality, accounting for the competing risks of left ventricular assist device placement and orthotopic heart transplantation. Models were adjusted for age, sex, CS severity, etiology, mechanical ventilation, creatinine, and sodium. Spearman correlation tested associations between sACE2 activity and 48 cytokines. Results: For the 682 patients included, the mean age was 56 (SD 15) with 27% being female. sACE2 activity was significantly higher in CS vs. sHF patients (median [IQR] 42.5 [21.9 to 76.7] ng/mL vs. 25.3 [16.0 to 38.0] ng/mL, p< 0.001). In CS patients, elevated sACE2 activity (>28.5 ng/mL) was independently associated with mortality at six months (HR 1.92, 95% CI 1.15-3.83, p=0.020), one year (HR 1.80, 95% CI 1.13-2.86, p=0.013) and three years (HR 1.90, 95% CI 1.12-3.23, p=0.018) post-admission. Elevated sACE2 activity was not associated with mortality in sHF. sACE2 activity positively correlated with the concentration of pro-inflammatory cytokines IL6 (ρ=0.169, p=0.002), IL8 (ρ=0.229, p< 0.001), and CXCL10 (ρ=0.140, p=0.012). Conclusions: Soluble ACE2 activity is elevated in CS compared to sHF and is associated with long-term mortality in this population. Further studies are needed to assess the prognostic value of sACE2 and its role in identifying patients who may benefit from RAAS-modulating therapies.