Citations

PURPOSE Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen deprivation therapy for oligometastatic castration-sensitive prostate cancer (omCSPC). Most patients with bone metastatic (BM) omCSPC recur with additional bone disease after MDT. We hypothesized the BM-targeting alpha-emitter radium-223 dichloride (Ra223) could target subclinical bone disease and delay progression. METHODS This is an investigator-initiated, multicenter, open-label phase II RCT. Eligible men with recurrent omCSPC with ≥one bone metastasis (≤three on conventional imaging and/or ≤five on molecular imaging) were randomly assigned (1:1) to stereotactic ablative radiation (SABR) MDT alone or SABR MDT with Ra223 (six cycles). Primary end point was composite PFS. RESULTS From August 9, 2019, to March 2, 2023, 64 patients were randomly assigned, 33 to SABR MDT and 31 to SABR MDT/Ra223 balancing for key covariates. Most SABR MDT/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT/Ra223 (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.79 to 2.56]; P = .24). Seven patients (11%) experienced grade 3 treatment-related adverse events (no grade 4 or 5), 2 of 33 (6%) with SABR and 5 of 30 (17%) with SABR MDT/Ra223. Patients with high-risk (HiRi) pathogenic mutations in ATM , BRCA1/2 , RB1 , or TP53 had worse PFS (HR, 5.95 [95% CI, 1.83 to 19.3]; P = .003). Greater T-cell receptor (TCR) unique productive rearrangements were prognostic for improved PFS independent of the treatment arm (aHR, 0.45 [95% CI, 0.21 to 0.96]; P = .04). CONCLUSION Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR repertoire as prognostic biomarkers in omCSPC treated with SABR MDT, highlighting the importance of collecting biological correlates in RCTs for omCSPC.

OBJECTIVE Despite the use of multiple glucose-lowering medications, glycemic targets are not met in a significant fraction of people with type 2 diabetes. In this prospective, observational study we assessed the prevalence of hypercortisolism, a potential contributing factor to inadequate glucose control. RESEARCH DESIGN AND METHODS Individuals with type 2 diabetes and HbA1c 7.5%–11.5% (58–102 mmol/mol) on two or more glucose-lowering medications with or without micro-/macrovascular complications or taking multiple blood pressure–lowering medications were screened with a 1-mg dexamethasone suppression test. Common causes of false-positive DSTs were excluded. The primary end point was the prevalence of hypercortisolism, defined as post-DST cortisol >1.8 μg/dL (50 nmol/L). Characteristics associated with hypercortisolism were assessed with multiple logistic regression. The percentage and characteristics of participants with hypercortisolism and adrenal imaging abnormalities were also assessed. RESULTS Post-DST cortisol was unsuppressed in 252 of 1,057 participants (prevalence 23.8%; 95% CI 21.3, 26.5). Hypercortisolism prevalence was 33.3% among participants with cardiac disorders and 36.6% among those taking three or more blood pressure–lowering medications. Adrenal imaging abnormalities were reported in 34.7% of participants with hypercortisolism. Use of sodium–glucose cotransporter 2 inhibitors (odds ratio 1.558), maximum-dose glucagon-like peptide 1 receptor agonists (1.544), tirzepatide (1.981), or a higher number of blood pressure–lowering medications (1.390); older age (1.316); BMI <30 kg/m2 (1.639); non-Latino/Hispanic ethnicity (3.718); and use of fibrates (2.676) or analgesics (1.457) were associated with higher prevalence (all P < 0.03). CONCLUSIONS Hypercortisolism was associated with hyperglycemia in approximately one-quarter of individuals with inadequately controlled type 2 diabetes despite multiple medications.

Introduction: Online self-triage/symptom checkers are a relatively new e-Health modality. We aimed to evaluate the degree to which patient’s chosen symptom during the use of an online self-triage tool was congruent with that chosen by a nurse performing phone triage. Methods: Patient encounters from September 1, 2022, to September 30, 2023, were reviewed for patients who completed both online self-triage and a subsequent nursing phone triage within 24 hours. The symptoms chosen by the patient for their self-triage encounter and the symptoms chosen by the nurse during the subsequent nurse triage were reviewed. The symptoms chosen in these two triage encounters were then compared for congruency. A subset of our database was evaluated for congruency between the self-triage and the nurse phone triage endpoint recommendations. Results: There were 5,443 encounters meeting inclusion criteria to study for congruency between self-triage and nurse triage symptom choice. The range of time between self-triage and nurse triage ranged from 0 min to 1,439 min (23.9 hours) with a median of 23 minutes between self and nurse triage encounters. Symptom congruency between the two methods found 74.2% (4,038) to be completely congruent while 989 (18.2%) were somewhat congruent. Only 7.6% (416) had no apparent congruency. Out of 1,705 self and nurse triage dyads eligible for study for agreement between endpoint recommendations, 244 (14.3%) were under-triaged, 1,110 (65.1%) were triaged to the same level of care and 351 (20.6%) were over-triaged. Conclusion: Congruency between symptoms chosen by the patient for triage and nurse triage were highly congruent with only 7.6% of the sample showing no apparent congruency between the self-triage symptom and the nurse triage symptom. When compared to nurse triage, most self-triage endpoint recommendations were either triaged to the same level of care or were over-triaged to a higher level of care.

Purpose This study investigates medical students’ opinions on the optimal timing for taking the emergency medicine (EM) clerkship and its effects on preparedness for subsequent clerkships and the USMLE (United States Medical Licensing Examination) Step 2 examination. Methods A cross-sectional survey was conducted among third- and fourth-year students at the Mayo Clinic Alix School of Medicine. The survey collected opinions on the optimal timing for the EM clerkship and its impact on self-efficacy as well as perceived preparedness for future clerkships and the USMLE Step 2 examination. Results Only 5% of third-year EM clerkship students felt they would have been more prepared in their fourth year. Conversely, 70% of fourth-year students believed they were more prepared than if they had taken it in their third year. Students were evenly split on if an earlier EM clerkship would have been helpful for subsequent clerkships. 88% of pre-USMLE Step 2 students found it helpful for Step 2, while 37% of post-USMLE Step 2 students felt it would have helped their preparedness. Additionally, 96% of students stated the EM clerkship increased their confidence in seeing patients. 43% of those who took the clerkship in their fourth year reported they would have considered EM as a specialty had they taken it earlier. Most students recommended taking the EM clerkship during the second 6 months of clerkships. Conclusion There are mixed opinions among medical students regarding the helpfulness of taking the EM clerkship earlier for subsequent clerkships and USMLE Step 2 preparedness. However, the majority recommend taking the EM clerkship earlier. A significant proportion of participants would have considered EM as a specialty if they had taken the clerkship earlier. Furthermore, 96% reported increased self-efficacy. Therefore, encouraging students to take the EM clerkship earlier may increase self-confidence and allow for earlier career exploration.

Abstract Background: Rectosigmoid endometriosis (RSE) presents with a diverse array of MRI findings that impact surgical planning. No standardized reporting and data system has been established for RSE. Purpose: We propose a novel MRI scoring system designed to predict the likelihood of muscularis propria (MP) involvement in RSE, which would, in turn, influence surgical planning. Material and Methods: The records of patients with bowel endometriosis treated surgically from May 2018 to June 2022 were retrieved. Surgery was classified as partial thickness discoid, full thickness discoid, or segmental resection. Each pre-treatment MRI was scored based on the mutual agreement of two abdominal radiologists (reference score). The MRI score was defined as (1) score 0: no evidence of RSE, (2) score 1: minimal tethering involving the serosal surface without MP involvement, (3) score 2: intermediate soft tissue thickening involving the rectosigmoid colon with indeterminate MP involvement, or (4) score 3: definite mushroom cap sign or definite MP involvement. In the reader study, two radiologists independently scored each exam. The area under the curve (AUC) was evaluated for predicting the need for segmental or full thickness discoid resection. Results: The cohort consisted of 95 patients (median age: 36 years); 16, 14, 30, and 35 patients had MRI score 0, 1, 2, and 3, respectively. Patients with MRI scores 3 and 2 underwent partial thickness discoid (6% vs 50%), full thickness discoid (6% vs 17%), and segmental resection (89% vs 33%), respectively. All patients with MRI scores 1 or 0 either underwent partial thickness discoid resection or did not undergo rectosigmoid surgery. The AUCs were 92.2%, 84.5% and 93.9% for MRI scores of the reference, reader 1, and 2, respectively. Conclusion: Our MRI scoring system based on suspected depth of bowel invasion showed good diagnostic performance to predict the type of surgical intervention needed. Summary Statement This novel MRI scoring system for rectosigmoid endometriosis is a concise and qualitative scale based on suspected depth of bowel wall invasion to best guide operative planning.

ABSTRACTIntroductionThe diagnosis of antibody‐mediated rejection (AMR) requires input from several transplant professionals. Bringing clinical and laboratory experts together may help standardize care. Yet, little is known about current global practices of multidisciplinary meetings for AMR management.MethodsThe Banff Antibody‐Mediated Injury Working Group approached professional societies worldwide to distribute a survey on the availability, content, participants, perceived value, and barriers to the implementation of multidisciplinary meetings.ResultsFour hundred two transplant professionals from six continents caring for kidney (90.55%), liver (21.14%), pancreas (20.65%), heart (15.17%), and lung (14.18%) transplant recipients participated in the survey, and 302 (75.12%) reported attending multidisciplinary meetings. Multidisciplinary meetings were more prevalent in academic centers, in high‐ versus low‐to‐middle‐income regions (81.03% and 65.99%, respectively; p < 0.001), and in mid‐to‐large size transplant programs compared to smaller programs. Perceived value included continued professional development (97.68%) and trainee education (95.70%). AMR was reported to be discussed at these meetings by 217 respondents with case presentations reviewing patient characteristics, histology, and HLA antibody data. A third of the respondents reviewed non‐HLA/pathogenic autoantibodies and/or molecular diagnostics, with the latter being more frequently applied in high‐ versus low‐to‐middle‐income regions (46.71% and 12.31%, respectively; p < 0.001). AMR case presentations allowed diagnosis revision, actionable management plans and were perceived as improving care. The primary barrier to the implementation of multidisciplinary meetings (63.27%) was the unavailability of transplant professionals (e.g., transplant immunologists).ConclusionFacilitating multidisciplinary meetings through the remote participation of pertinent experts and incentivizing participation through remuneration, protected time, or continued medical education may help standardize AMR diagnosis and harmonize its management.

ABSTRACT Long segment losses exceeding 10 cm in the sciatic nerve are challenging in both the reconstructive techniques and optimizing sensory and motor function recovery. This case report and literature review describes our experience of using a pedicled vascularized common peroneal nerve graft to repair a 14‐cm sciatic nerve defect, involving L4 , L5 , and S1 nerve roots. Additionally, we conducted a literature review of various types of nerve autografts for large sciatic nerve defects, summarizing their characteristics and outcomes to aid clinicians in decision‐making and expected results in different scenarios. The patient, a 23‐year‐old female diagnosed with neurofibromatosis type I, underwent R0 tumor resection of the proximal left sciatic nerve due to a malignant peripheral nerve sheath tumor. She received an ipsilateral pedicled vascularized common peroneal nerve graft. The reconstruction included the L4 , L5 , and S1 nerve roots beyond the greater sciatic foramen into the inner pelvis. The patient's postoperative course was uneventful. At the 26‐month follow‐up, she showed MRC grade 4/5 strength in hamstrings with 90°knee flexion and a steady gait pattern. At the 32‐month follow‐up, she could ambulate very well with an ankle‐foot orthosis. The outcomes support the use of a pedicled vascularized common peroneal nerve graft in a single‐staged surgery to restore motor function for large sciatic nerve defects. Our literature review revealed that in cases where sural nerves are insufficient or injured for sciatic nerve reconstruction, the common peroneal nerve is a viable alternative to help patients regain functional independence.