Montreal General Hospital

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder lacking disease-modifying therapies, and its management is limited by the absence of accessible biomarkers for disease progression and treatment response. We implemented an ultra-deep plasma proteomics workflow integrating Mag-Net extracellular vesicle enrichment with Orbitrap Astral mass spectrometry to profile longitudinal samples from PD patients. This approach quantified 6,481 plasma proteins, an unprecedented depth in PD studies, revealing distinct signatures associated with disease duration and dopaminergic therapy exposure. Candidate biomarkers were validated in an independent cohort using ELISA, demonstrating predictive utility in AI-driven models. To uncover mechanistic drivers, we intersected proteomic data with our new genome-wide overexpression screens for regulators of alpha-synuclein pre-formed fibril uptake, identifying MFN2, PSMD4, and EIF4G1 as major hubs that link systemic proteomic changes to mitochondrial dynamics and proteostasis. Additionally, a meta-analysis of brain transcriptomes responsive to Levodopa (L-DOPA) treatment identified 42 candidate genes, including NDUFS4, GNAS, TSC1, and NTS, some of which are targets of approved therapeutics. Finally, an integrative network analysis revealed that key pathological hubs, such as CD14, IFNG, and PLAT, are targets of approved pharmacological agents. Overall, these findings provide a systems-level resource for PD biomarker discovery and reveal druggable pathways for precision medicine strategies aimed at improving therapeutic outcomes.

Abstract Background Mirikizumab is approved for adults with moderate-to-severe ulcerative colitis (UC) based on evidence from randomised clinical trials.1 However, real-world evidence on treatment persistence and clinical outcomes in routine practice is limited. This analysis evaluated treatment persistence and effectiveness among patients with UC receiving mirikizumab in a Canadian real-world setting. Methods Adults (≥18 years) with moderate-to-severe UC enrolled in the LillyPlus® Patient Support Program in Canada who received at least 1 dose of mirikizumab (index date) between 26 October 2023 and 28 April 2025 were included. Persistence was defined as continuous mirikizumab treatment until reported discontinuation.2 Clinical outcomes assessed included bowel urgency (BU; scored 0-10), rectal bleeding (RB; scored 0-3), and stool frequency (SF; scored 0-3), with higher scores indicating more severe symptoms/higher symptom severity. Scores were collected at baseline and at weeks 4, 12, and 24 (+4-week window after each touchpoint). Persistence and clinical outcomes were evaluated up to 24 weeks post-index by prior advanced therapy (AT) subgroup (AT-naïve and AT-experienced) using descriptive statistics. Results The cohort (N = 774) was 51.9% female with a mean (standard deviation [SD]) age of 46.5 (17.4) years, and 87.0% of participants were AT-experienced. Treatment persistence rates were 98.0%, 92.6%, and 80.9% at 4, 12, and 24 weeks, respectively (Figure 1). Persistence rates trended higher in AT-naïve than in AT-experienced patients at week 24. At baseline, the overall mean (SD) BU, RB, and SF scores were 6.83 (2.90), 1.41 (1.08), and 2.22 (1.05), respectively (Figure 2). Changes to outcome scores were observed as early as week 4. By week 24, the overall mean (SD) BU, RB, and SF scores had decreased to 2.98 (2.67), 0.44 (0.72), and 0.86 (0.92), respectively. Conclusion In this real-world setting, which included a high proportion of AT-experienced participants (87.0%), mirikizumab demonstrated treatment persistence through 24 weeks of initial treatment. Improvements in BU, RB, and SF scores were observed as early as 4 weeks and continued over 24 weeks in both AT-naïve and AT-experienced patients.

The prevalence of overweight/obesity (OW/OB-defined by body mass index) in low- and middle-income countries is rising, and the sociodemographic characteristics of the most affected populations are changing. The relationship between education, widely recognized as a gender-related variable, and OW/OB in high-income countries is well understood; however, the impact in South Asian (SA) countries is less clear. This systematic review interrogated the relationship between educational attainment and OW/OB, by searching Ovid MEDLINE, CINAHL, EMBASE, and Web of Science for studies published after 2013, reporting the prevalence of OW/OB by educational attainment in eight SA countries. Data were extracted and the association between education and OW/OB was coded as direct, indirect, null, or U-shaped. A total of 32 studies were included in the review. The mean age was 38.5 years. The prevalence of OW/OB ranged between 4.6% and 64.4%. Females were reported to be at higher risk of OW/OB compared with males. Most of the studies reported women with higher education at greater risk of being OW/OB. SA countries are undergoing substantial transformations in their economic and social frameworks that influence how sex and gender mediate cardiovascular risk factors like OW/OB. Preventive strategies must be tailored to the unique characteristics of the SA population.

The most prevalent conditions affecting the pelvic floor include fecal incontinence (FI) and urinary incontinence (UI), both of which are particularly common among women with obesity. Although the effect of metabolic bariatric surgery (MBS) on FI remains a topic of ongoing discussion, the present study seeks to assess the impact of effective bariatric surgery on UI and FI in women with obesity. An observational prospective study was conducted at the Tours University Hospital, involving 212 women who underwent MBS. Participants completed pre-operative and post-operative questionnaires to evaluate UI and FI one-year after surgery. Additionally, urinary symptom profile (USP) and Wexner score (WS) were utilized for the assessment of UI and FI, respectively. Of the 212 patients, 148 achieved a weight loss of more than 20% of their weight one-year after surgery, and of these 40 (27.0%) completed all questionnaires. The median pre-surgical BMI was found to be 41.8 kg/m², which reduced to 29.1 kg/m² one-year post-surgery. A significant improvement was observed in stress urinary incontinence (SUI), which decreased from 32.5% pre-operatively to 22.5% post-operatively (p < 0.0001). FI showed slight exacerbation, with an increase in moderate FI (from 5.0% to 10.0%), frequency of liquid stool per week (from 2.5% to 5.0%), and gas-related symptoms (from 0 to 2.5%). The findings of this study indicate that MBS significantly improves SUI in women with obesity, yet has minimal impact on FI one-year postoperatively. Further studies are required to more accurately assess the impact of metabolic bariatric surgery on postoperative FI.

Compliance with training protocol is essential to achieve physiologic improvements associated with exercise. This study aimed to assess the compliance and response to a 4-week high-intensity interval training (HIIT)-based protocol as part of a multimodal prehabilitation program for patients with colorectal cancer awaiting surgery and to explore potential associated factors. The study analyzed 136 patients allocated to a prehabilitation exercise training program in a multicenter prehabilitation program. Compliance with training was defined based on intensity and time in HIIT during each session. Response to training was considered if patients increased peak oxygen uptake (VO2peak) ≥10 % or >2.5ml/kg/min after training. Data compliance was available for 104 patients. Non-compliant participants (n = 37, 35.6 %) had lower cardiorespiratory fitness (CRF) at baseline (mean difference, -2.74 ml/kg/min; p < 0.01) and tended to be older (p = 0.053). Approximately one of four patients exhibited a clinically meaningful response to exercise. Younger patients and those with lower CRF at baseline had greater odds of responding to training (Epx[B], 0.739; 95 % confidence interval {CI}, 0.58-0.93]) and Exp(B), 476 [95 % CI, 0.266-0.85 respectively). Furthermore, patients who increased VO2peak at least 2.5Mml/kg/min had no severe complications (Comprehensive Complication Index [CCI], ≤20) and experienced better postoperative recovery than the non-responding patients (p = 0.043 and p < 0.001 respectively). Compliance with a HIIT protocol among colorectal cancer patients was found to be affected by baseline CRF and age. Only one of four patients showed a clinically significant improvement in VO2peak after training, which was associated with less severe postoperative complications.

Limited operating room access in publicly funded institutions, particularly for emergencies, highlights the need for improved prioritization rules for common pathologies, including acute cholecystitis (AC). We compared the performance of our institution's surgical prioritization rules to the Tokyo diagnostic criteria and to develop a novel decision rule to predict AC on surgical pathology. All adult patients undergoing emergency cholecystectomy (EC) at a single academic institution (2017-2021) were reviewed. The primary outcome was the diagnosis of acute inflammation on final pathologic analysis. Multiple logistic regression was performed with a training subset using relevant clinical variables that were selected a priori. A simple weighted decision rule was created and compared to the Tokyo Guidelines and the institution's existing prioritization rules via an analysis of receiver operator curves. Among 756 patients undergoing EC, 97.6% met the criteria for AC as per Tokyo diagnostic criteria. Urgent booking category (area under the curve [AUC] = 0.58, sensitivity 89%, specificity 26%) and Tokyo criteria (AUC = 0.51, sensitivity 99%, specificity 3%) poorly discriminated for acute inflammation on final pathology. Discrimination of the hospital's case prioritization rules was moderate (AUC = 0.63, sensitivity 48%, specificity 78%), and a new decision rule was significantly higher (AUC = 0.71, sensitivity 72%, specificity 64%, P < 0.003). The Tokyo Guidelines were highly sensitive but nonspecific for the presence of acute inflammation on final pathology. An existing institutional case prioritization rule demonstrated moderate discrimination but was outperformed by a new rule incorporating clinical exam, fever, degree of leukocytosis, and inflammatory changes on imaging. These findings may aid AC prioritization in busy centers, though external validation is needed.

Objectif : Évaluer le degré de mise en œuvre de l’entente de pratique avancée en partenariat (EPAP) et ses répercussions sur le travail du pharmacien du CIUSSS du Centre-Ouest-de-l’Île-de-Montréal. Description de la problématique : L’EPAP est déployée dans plusieurs établissements de santé du Québec, y compris dans 16 secteurs cliniques du CIUSSS du Centre-Ouest-de-l’Île-de-Montréal. Cependant, il existe peu de données sur la pratique avancée en pharmacie. Un processus en trois étapes a été mis en place, incluant la comptabilisation des prescriptions issues de l’EPAP, l’envoi d’un questionnaire auto-administré et la réalisation d’entrevues auprès des pharmaciens pour explorer l’utilisation et les limites de l’EPAP. Cette démarche a permis de mettre en évidence une consignation insuffisante des actes cliniques et un manque de sensibilisation des pharmaciens aux nouvelles pratiques rendues possibles par l’entente de pratique avancée. Résolution de la problématique : Une augmentation de la consignation des actes effectués dans le cadre de l’EPAP a été notée à la suite de la présentation des données sur l’utilisation de l’EPAP, d’une discussion structurée avec les départements pour en standardiser l’application et de la diffusion de cartes-résumés aux postes des pharmaciens. Conclusion : Ce projet a permis aux pharmaciens de prendre davantage conscience des nouvelles pratiques possibles grâce à l’entente de pratique avancée. Cependant, des défis persistent concernant la sensibilisation des professionnels de la santé et la consignation des actes relevant de l’EPAP, éléments essentiels pour valoriser pleinement le rôle des pharmaciens prescripteurs. Abstract Objective: To assess the degree of implementation of the Advanced Practice Partnership Agreement (APPA) and its impact on the work of pharmacists at the CIUSSS du Centre-Ouest-de-l’Île-de-Montréal. Problem Description: The APPA has been deployed in several healthcare institutions across Quebec, including 16 clinical sectors of the CIUSSS du Centre-Ouest-de-l’Île-de-Montréal. However, there is limited data on advanced pharmacy practice. A three-step process was implemented, including the tracking of prescriptions issued under the APPA, the distribution of a self-administered questionnaire, and interviews with pharmacists to explore the use and limitations of the APPA. This approach highlighted insufficient documentation of clinical activities and a lack of awareness among pharmacists regarding the new practices enabled by the agreement. Problem Resolution: An increase in the documentation of activities performed under the APPA was observed following the presentation of data on APPA usage, structured discussions with departments to standardize its application, and the distribution of summary cards at pharmacists’ workstations. Conclusion: This project helped pharmacists become more aware of the new practices made possible by the Advanced Practice Partnership Agreement. However, challenges remain in raising awareness among healthcare professionals and in documenting activities related to the APPA, both essential for fully recognizing the role of prescribing pharmacists.