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The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014–2019; 2019–2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them. Responding to the needs of researchers within the CCNA teams, a unique sample of 1173 deeply phenotyped patients with various forms of dementia was accrued and studied over eight years (COMPASS-ND). In the second phase of funding (2019–2024), a national dementia prevention program (CAN-THUMBS UP) was set up. In a short time, this prevention program became a member of the World Wide FINGERS prevention consortium. In this article, the challenges, successes, and impacts of CCNA in Canada and internationally are discussed. Short-term deliverables have occurred, along with considerable promise of impacts in the longer term. The creation of synergy, networking, capacity building, engagement of people with lived experience, and economies of scale have contributed to the considerable success of CCNA by all measures. CCNA is evidence that an organized “centrally-organized” approach to dementia research can catalyze important progress nationally and yield significant and measurable results.

Importance Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined. Objective To develop consensus best practices for delivering NT to patients with localized PDAC. Design, Setting, and Participants This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders. Main Outcome and Measures Statements that reached 75% agreement or greater were included in final consensus statements. Results Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3). Conclusions Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice.

Blood flow restriction (BFR) is a popular resistance exercise technique purported to increase metabolic stress and augment training adaptations over time. However, short-term use may lead to acute neuromuscular fatigue and higher exertion ratings. Objective: The purpose of the current study was to examine acute physiological responses to low-load resistance exercise utilizing BFR compared to higher-load, non-BFR resistance exercise. Methods: Recreationally trained males (n = 6) and females (n = 7) (mean ± standard deviation, age: 20 ± 1 yrs.; height: 172 ± 8 cm; weight: 73 ± 11 kg; BMI: 24.4 ± 2.2 kg·m−2; training experience: 4 ± 2 yrs.) had limb occlusion pressure determined (50%; right leg: 118 ± 11 mmHg; left leg: 121 ± 13 mmHg) using an automated, self-inflating cuff system during baseline testing. In subsequent sessions, using a randomized, cross-over design, participants completed one of two experimental conditions: (1) Low-load + BFR and (2) High load + non-BFR. In both conditions, participants completed one set of back squats at either 30% (BFR) or 60% (non-BFR) of an estimated 1RM for a max of 30 repetitions, followed by three additional sets with the same loads and a target of 15 repetitions per set. Blood lactate and countermovement jump (CMJ) height were measured pre- and post-back squat. Ratings of perceived exertion (RPE) were assessed following each set. Results: When collapsed across all sets, participants completed significantly more total repetitions in the BFR condition compared to non-BFR (75.0 ± 0.0 vs. 68.23 ± 9.27 reps; p = 0.015; ES: 1.03), but a lower training load volume (2380 ± 728 vs. 4756 ± 1538 kg; p < 0.001; ES: 1.97). There was a significant time-by-condition interaction (p < 0.001), with a greater increase in blood lactate occurring from baseline to post-back squat in the non-BFR condition (11.61 mmol/L, 95%CI: 9.93, 13.28 mmol/L) compared to BFR (5.98 mmol/L, 95%CI: 4.30, 7.65 mmol/L). There was another significant time-by-condition interaction (p = 0.043), with a greater reduction in CMJ occurring in the non-BFR condition (−6.01, 95%CI: −9.14, −2.88 cm; p < 0.001) compared to BFR (−1.50, 95%CI: −1.50, 4.51 cm; p = 0.312). Conclusions: Utilizing a low-load BFR protocol may allow for a higher training volume, yet lower metabolic stress and reduce neuromuscular fatigue compared to lifting at a higher load without the use of BFR.

The National Cancer Database (NCDB) collects data from approximately 1,500 Commission on Cancer (CoC) facilities and represent 73.7% of newly diagnosed cancers nationwide. The American College of Surgeons Cancer Program developed it first annual report from the NCDB 2021 participant user file reporting new observations and recent trends of cancer diagnoses, patient demographics, and treatments as well as an in-depth report on treatment and outcomes in breast, pancreas, and colon cancers. Of the 1,328,131 cancers diagnosed in 2021 at 1,281 reporting CoC hospitals, one-fifth continue to be female breast cancer. In 2021, the NCDB’s 5 most common adult cancers were breast, prostate, lung, colon, and melanoma and varied by patient sex. Use of neoadjuvant systemic therapy increased in recent years in pancreas, breast, and urinary bladder cancer, although a slight decrease in pancreas and breast cancer was observed in 2021. Breast cancer has high survival rates, especially in lower-stage disease and estrogen receptor-positive/human epidermal growth factor receptor 2-negative disease. There is increase in neoadjuvant systemic therapy use, especially in human epidermal growth factor receptor 2-positive disease and estrogen receptor-negative disease. Colon cancer presents most commonly as stage III or II with a primary in the cecum or ascending colon in 38.9%. The majority are microsatellite instability stable, Kirsten rat sarcoma viral oncogene homologue normal, and CEA positive. Survival is most dependent on stage but also associated with microsatellite instability stability, abnormal Kirsten rat sarcoma viral oncogene homologue, and positive CEA. Pancreatic cancer presents with stage IV disease in nearly half, although an increase in stage I disease is seen. The most common location is pancreatic head. Survival is relatively low and most dependent on stage.

Abstract Background and Aims Active inflammatory bowel disease (IBD) at conception is associated with adverse pregnancy outcomes. International guidelines address antenatal care, but contraception counseling and risk assessment are not addressed. Data on healthcare professionals’ guidance for women with IBD regarding contraception are scarce. We aimed to describe contraceptive use, preferences, knowledge, and barriers among women with IBD. Methods A 34-item questionnaire was administered to female IBD patients aged 18-45. Disease control was measured using PRO-2 and IBD-control questionnaire, and contraceptive preferences were assessed by the contraceptive features survey. Logistic regression explored associations between contraceptive use, attitudes, disease remission status, and other factors. Results Of 338 women surveyed, 243 (74%) used some form of contraception. Oral birth control pills (28%) and barrier methods (18%) were most used but 20% used long-acting methods. Women with active disease were more likely to use long-acting contraception (23%) compared to those in remission (17%). Contraceptive priorities were effectiveness (78%), ease of use (75%), and minimal side effects (68%). Only 25% women had discussed reproductive issues with their IBD clinician, though 85% were comfortable to do so. Preferred sources for reproductive counseling were IBD nurses (79%), general practitioners (75%), IBD doctors (68%), and gynecologists (49%). Conclusions A quarter of women with IBD were not using any contraception, and long-acting contraceptive use was low. Women prefer effective, easy-to-use contraceptives with minimal side effects but lack knowledge on effective contraception-related issues. Better education and proactive discussions between healthcare providers and patients could improve reproductive health in women with IBD.

INTRODUCTION: Perception of the ascites burden and its effects on quality of life may be different between sexes. This study assessed sex differences in perception of ascites burden and its impact on health-related quality of life (HRQoL) in patients with recurrent or refractory ascites. METHODS: The North American Consortium for the Study of End-stage Liver Disease prospectively enrolled outpatients with cirrhosis and large ascites requiring repeat large volume paracenteses. Demographics, laboratory results, comorbidities, medications, frailty measurements, and self-reported questionnaires related to functional status, physical activities, and HRQoL (generic = Short Form 36 and ascites specific = Ascites Questionnaire) were compared between sexes. RESULTS: In total, 392 men (59.6 ± 10.7 years) and 184 women (59.5 ± 11.1 years) with predominantly alcohol-related liver disease (51% and 43%, respectively) and median Model for End-Stage Liver Disease-Na: 13 were enrolled. Both groups had similar comorbidities and cirrhosis complications, ascites duration and severity, and frailty scores ( P = 0.94). Women had more symptoms related to their ascites (Ascites Questionnaire score = 66 ± 21 vs 60 ± 21 in men, P = 0.001) (higher value = feeling worse). 35% of women felt depressed vs 22% of men ( P = 0.0009), with lower mental but not physical functioning components of Short Form 36 ( P = 0.019). Women continued to conduct their daily activities as adequately as men as indicated by Duke Status Activity Index ( P = 0.27) and Godin Leisure Activity Index ( P = 0.47). DISCUSSION: Women with cirrhosis and ascites experienced worse emotional HRQoL than men without difference in daily function. Our analyses underscore the differences in the lived experience of women vs men with cirrhosis and highlight the need for patient-reported metrics to provide patient-centered care.

The Neurohospitalist Core Competencies comprise a set of competency-based learning objectives that encapsulate the knowledge, skills, and attitudes of neurohospitalitists who specialize in the care of hospitalized patients with neurologic conditions. These competencies serve to characterize the rapidly expanding field of neurohospitalist medicine. The 27 chapters are divided into 3 sections entitled: neurological conditions, clinical interventions and interpretation of ancillary studies, and neurohospitalist role in the healthcare system. Each individual learning objective in the chapters describes a specific concept with an action verb to illustrate the behavior that the neurohospitalist exhibits. The individual neurohospitalist may not exhibit mastery in each of the topics included as individual practices vary in scope and practice pattern. A few examples of how the complete set of competencies may be used include in the creation of curricula for neurohospitalist fellowships, to assist in defining the scope of practice of neurohospitalists for administrative leaders of hospitals and departments, and in influencing the direction of further research and quality improvement in the field.

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive, malignant embryonal tumor with dismal long-term survival despite aggressive multimodal therapy. While this tumor typically presents in infancy or early childhood, there are published case reports of adult-onset ATRT. Making prognostic conclusions or therapeutic decisions for this older patient population remains challenging due to the paucity of these reports. A 25-year-old female with Down syndrome presented with dysphagia and facial droop and was found to have an avidly enhancing, cerebellopontine angle mass. Histology demonstrated sheets of rhabdoid cells with loss of INI1 expression, pathognomonic for ATRT. Further sequencing detected a frameshift SMARCB1 mutation and methylation profiling matched with high confidence to the MYC subclass of ATRT. The patient was treated with subtotal surgical resection and focal proton beam irradiation, followed by chemotherapy on a modified regimen due to concern for heightened risk of treatment-related toxicity. On most recent follow-up 22 months from diagnosis, the patient remains without evidence of disease. This report represents the first known case of ATRT in a young adult patient with Down syndrome, offering unique mechanistic insight into the tumorigenesis of ATRT. Further studies are needed to define an appropriate risk-adapted and standardized therapeutic approach for this patient population.

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility. Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Demographic, preoperative physical examination, and radiographic data were collected from a multicenter national prospective cohort of patients with OCD of the knee. Inclusion criteria included patients <19 years of age and patients with arthroscopically confirmed mobility status based on the Research on Osteochondritis Dissecans of the Knee arthroscopy classification. Multivariable logistic regression analysis using stepwise model selection was used to determine factors associated with the likelihood of a mobile versus an immobile lesion. A 75% partition of the data was used for model training, and 25% was used as a validation cohort. Quantitative model fit statistics were computed using the holdout data, including sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), along with the corresponding 95% CI. Results: A total of 407 patients in the prospective cohort met inclusion criteria, and 62% were male. The mean ± SD age was 13.7 ± 2.2 years, height 161.8 ± 5.3 cm, and weight 59.2 ± 42.2 kg. Arthroscopic evaluation yielded 235 immobile and 172 mobile lesions. Multivariable analysis determined that the best model to predict lesion mobility included chronologic age ≥14 years ( P < .001), effusion on physical examination ( P < .001), and any loss of range of motion on physical examination ( P = .07), while controlling for male sex ( P = .38) and weight >54.4 kg ( P = .12). In the 25% holdout validation sample (n = 102), a sensitivity of 83%, a specificity of 82%, and an AUC of 0.89 (95% CI, 0.82-0.95) were achieved with these predictive factors. Conclusion: Age, effusion, and loss of motion can predict knee OCD lesion mobility at the time of arthroscopy. Education about lesion mobility can help with surgical planning and patient and family counseling.