Citations

Reasonable accommodations in higher education are being more frequently requested by graduate occupational and physical therapy students within didactic and clinical contexts. Researchers aimed to describe the experiences of clinical educators in occupational and physical therapy mentoring graduate students with a disclosed accommodation during terminal clinical education, employing a qualitative design. Semi-structured interviews and one-time electronic survey were completed. Reflexive thematic analysis was conducted following the approach described by Braun and Clarke. Twelve occupational or physical therapy clinical educators participated in semi-structured interviews, each having mentored 1–2 students with a disclosed disability accommodation during a terminal clinical education experience. Four major thematic categories regarding accommodation use in terminal clinical emerged: 1) accommodation process, 2) team approach to accommodating, 3) fostering accommodations, and 4) ambiguity in facilitating accommodations. Clinical educators emphasized the importance of being informed about accommodations well in advance, adapting teaching methods, and maintaining regular communication between academic institutions, clinical sites, and students. Training for clinical educators on the disclosure process, legal obligations, and strategies for effective mentorship to ensure alignment of accommodation, academic requirements, and site expectations is essential.

RET fusions appear in 1%-2% of non–small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385 ) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET -altered NSCLC and RET fusion–positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion–positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion–positive NSCLCs, confirming previous findings with longer follow-up.

Abstract Background Valve-sparing aortic root replacement has increasingly been performed in Marfan patients. However, there is ongoing debate on whether the non-aneurysmal sized aortic arch should be prophylactically replaced during the index operation. The aim of our retrospective single-centre study was to investigate the long-term status of the aortic arch in these patients. Methods Between 1993 and 2021, a total of 723 patients underwent valve-sparing aortic root replacement with a straight tube graft (David I reimplantation) at our institution; 119 patients had confirmed Marfan disease. Of these 119 Marfan patients, 67 patients had isolated aortic root aneurysm with no aortic arch pathology. These 67 patients underwent isolated David I procedure in an elective setting (only aortic root and ascending aortic replacement) without any concomitant procedures and were included in the present study. Results This study includes 67 patients with Marfan syndrome who underwent isolated elective valve-sparing aortic root replacement. The median age of patients was 30 years (20-41), and 47 were male (70%). The cardiopulmonary time was 157.5 (145.8-178.3) min, and aortic clamp time was 117.0 ± 19.8 min. The in-hospital mortality and stroke rates were both 0%. Follow-up was 100% complete. Survival at 1, 5, 10, 15, and 20 years were 100%, 100%, 93%, 89%, and 85%, respectively. Freedom from aortic arch reoperation due to aneurysm at 1, 5, 10, 15, and 20 years was 100%, 100%, 100%, 100%, and 95%, respectively. In follow-up, no patient required aortic arch replacement due to aortic arch aneurysm. A total of 3 patients underwent aortic arch replacement for type B aortic dissection. Of these 3 patients, 1 had chronic type B dissection with aortic aneurysm, and 2 had acute type B dissection. Conclusions The long-term results after valve-sparing aortic root replacement with a straight tube graft (David I procedure) in Marfan patients are excellent. Our study shows that the risk for future aortic arch intervention after elective valve sparing aortic root replacement in Marfan patients is extremely low. Hence, our study supports the idea that concomitant prophylactic aortic arch replacement during elective valve sparing aortic root replacement in Marfan patients with non-aneurysmal aortic arch is not necessary.

Abstract Introduction We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks. Methods Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment. Results In the pooled population (n = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause. Conclusions Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification.

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. Design, Setting, and Participants Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. Main Outcomes and Measures Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. Results In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. Conclusions and Relevance Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

Abstract Study question What does the collaborative document on adenomyosis terminology, classification, and diagnosis by ESGE, ESHRE, and WES provides? Summary answer This good practice recommendations paper offers guidance on the technical aspects, terminology, classification, and diagnosis of adenomyosis in women of reproductive age. What is known already The existing literature on adenomyosis terminology is heterogeneous and confusing. Various classification systems based on ultrasound and MRI have been proposed, yet none have gained international acceptance or clinical validation. The contradictory data on the diagnostic accuracy of these modalities further complicate adenomyosis diagnosis in reproductive-age women. Study design, size, duration A working group from ESGE, ESHRE, and WES has collaborated to write recommendations concerning the terminology, classification, and diagnosis of adenomyosis. Participants/materials, setting, methods Focusing on terminology, classification, and diagnosis, this good practice paper paves the way for further recommendations on the management and surgical treatment of adenomyosis in reproductive-age women. Main results and the role of chance The document overviews adenomyosis terminology and reviews proposed classification systems based on histology, ultrasound, and MRI, concluding with diagnostic recommendations. Limitations, reason for caution Owing the scarcity of evidence, these recommendations predominantly rely on clinical expertise. Wider implications of the findings The recommendations aim to enhance existing adenomyosis guidelines. Study funding/Competing interests All costs were covered by ESHRE funds, with no external funding for the development process or manuscript production.