Citations

Abstract Anterior shoulder instability is a common cause of shoulder pain and dysfunction in young patients and may be associated with concomitant bony and soft tissue pathology. Humeral avulsion of the glenohumeral ligament (HAGL) and rotator cuff tears are often seen in the setting of traumatic anterior shoulder instability events, especially in patients over 40 years of age, and portend poor postoperative outcomes if not addressed appropriately. While arthroscopic repair of rotator cuff tears is standard of care, both arthroscopic and open approaches for HAGL repair have been described and are associated with good clinical outcomes. Open HAGL repair affords the ability to address additional pathologies, including subscapularis tears and biceps tendon tears/SLAP tears with open subpectoral tenodesis, with direct visualization of the tear, while affording protection of the neurovascular structures. In this Technical Note, the authors describe their preferred technique for combined arthroscopic rotator cuff tear and open HAGL repair. Technique Video video See video under supplementary data.

Abstract Background: Responsiveness to mood-stabilizing pharmacotherapy varies in bipolar disorder (BD). We investigated clinical correlates of second-generation antipsychotic (SGA) treatment response and conducted the first genome-wide association study (GWAS), including exploratory polygenic scores (PGS), of SGA pharmacogenomic treatment response in BD. Methods: Treatment response was quantified using the Alda scale, and GWAS was performed using Alda-A score, controlling for sex, genotyping batch, and the genomic principal components. Results: The cohort included 2,159 adults with BD (1,416 BD-I, 691 BD-II, 51 schizoaffective BD), mean age 41.8 years, 62% female, 84% white, and 14% Hispanic. Nearly half (48%) were treated with SGAs. Current SGA users were younger (41.2±14.7 vs. 42.5±15.3 years, p =0.040), more likely to be Hispanic (14% vs. 11%, p =0.047), had a higher body mass index (BMI; 30.4±7.6 vs. 29.5±7.1 kg/m 2 , p =0.005). Lifetime comorbidity patterns for current SGA users include higher rates of manic psychosis (29% vs. 17%, p <0.001) and eating disorders — Anorexia Nervosa (7% vs. 4%, p =0.003), Bulimia Nervosa (7% vs. 4%, p =0.003), and Binge Eating Disorder (14% vs. 11%, p =0.030). We detected a genome-wide significant association between SGA Alda-A scores and GAS7 variants (top variant: rs202127418, β =-2.998, p =4.96E-08). However, SGA response was not significantly associated with PGS for schizophrenia, BD, and major depression (FDR>0.05). Conclusions: SGAs are frequently utilized as mood stabilizers in patients with BD and are associated with manic psychosis and eating disorders. GAS7 variants may predict SGA response, but larger, more diverse cohorts are needed for validation.

Abstract Purpose : While it’s commonplace in medical education to train learners using simulated patient encounters, task trainers, or by practicing skills on healthy volunteers, little is known about how well learning and skills transfer to patient care. The purpose of this research is to quantify Point-of-Care Ultrasound (POCUS) skill transfer to patient care through performance assessment. Method : A quantitative analysis of aggregated data consisting of image quality of student-performed POCUS examinations from one midwestern Physician Assistant program was performed. Probabilities for scores of 1-2, 3, 4, and 5 were estimated using a multivariable cumulative logit model. Results : Forty-six PA students were included in the study. A total of 6,218 POCUS examinations were included; 4,506 on non-patients, and 1,712 on patients. When evaluating skill transfer from non-patients to patients, the probability of obtaining a high-quality examination decreases significantly, with a more substantial decrease in performance on more complex skills. The probability of a high-quality examination on the twenty-fifth examination was the highest when learning transfer happened earlier. Conclusion : While training medical providers using non-patient experiences is common, educators must understand the significant loss of quality upon skills transfer to patient care. More complex or higher risk skills likely require close monitoring at the point of skill transfer, to support the learner and ensure patient safety. Based on the findings of this research, earlier skill transfer is associated with worse immediate performance but better long-term re-learning outcomes. Increased deliberate practice prior to skill transfer is associated with better first-time performance on actual patients.

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients.

The NCCN Clinical Practice Guidelines (NCCN Guidelines) for Wilms Tumor (WT; nephroblastoma) cover strategies for the screening, diagnosis, and treatment of WT, which is the most frequent primary kidney tumor in children. WT can generally be separated into 2 histology types: favorable histology WT and anaplastic WT. Five-year survival is high for children with favorable histology WT who receive appropriate treatment; however, survival rates are much lower for patients who present with higher stage diffuse anaplastic WT. Treatment of WT can range from surgery alone to surgery plus intensive chemotherapy and radiation depending on whether the tumor is unilateral or bilateral, histology, and local stage. The goal of therapy is to maximize cure while minimizing long-term toxicities. The content featured in this issue covers the NCCN panel’s recommendations for overall management of both favorable histology WT and anaplastic WT.

The NCCN Guidelines for Uterine Neoplasms provide recommendations for diagnostic workup, clinical staging, and treatment options for patients with endometrial cancer and uterine sarcoma. The NCCN Cervical Uterine Panel meets at least annually to review comments from reviewers within their institutions; examine relevant new data from publications, abstracts, and recent FDA approvals; and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s deliberations on the new FIGO 2023 staging system and updates on the new systemic therapy recommendations for the management of endometrial cancer.

Abstract Background Direct measurement of low-density lipoprotein cholesterol (LDL-C) is widely used and recommended by professional society guidelines despite its potential limitations in patients with hypertriglyceridemia and low LDL-C. This study evaluated the performance of 3 direct LDL-C (LDL-CD) assays, 2 modern LDL-C calculation methods [LDL-C Martin (LDL-CM), LDL-C modified Sampson (LDL-CS)] and the conventional Friedewald (LDL-CF) method against the reference method, beta-quantification (LDL-CBQ). Methods A total of 181 remnant sera from patients with standard lipid panel orders or from patients with LDL-CBQ orders with triglycerides (TG) ≥ 400 mg/dL (4.5 mmol/L), or with TG ≥ 150 mg/dL (1.69 mmol/L) and LDL-C &lt; 70 mg/dL (1.8 mmol/L) were included. LDL-CD and lipid panel data were gathered from Abbott Alinity, Roche Cobas, and Siemens Atellica platforms. Results LDL-CD among the 3 platforms showed a median CV of 11.2%. In patients with TG &lt;400 mg/dL, LDL-CM and LDL-CS demonstrated less bias and less misclassification at the clinical decision LDL-C levels than LDL-CF or LDL-CD. In the 400 to 800 mg/dL (9.0 mmol/L) TG group, LDL-CS was superior to LDL-CD or LDL-CM in accuracy. When TG is ≥ 800 mg/dL, LDL-CD (Roche) showed substantial bias from LDL-CBQ while LDL-CS (Roche) showed smaller but significant bias. Conclusions In summary, LDL-CD or LDL-CF showed little advantage over the 2 modern LDL-C calculation methods. LDL-CS showed the best overall correlation with LDL-CBQ and therefore is recommended to replace LDL-CF and potentially LDL-CD when making clinical decisions in patients with low LDL-C and hypertriglyceridemia.

Abstract Background Malignant peripheral nerve sheath tumors (MPNSTs) are rare, aggressive sarcomas, with 40% associated with neurofibromatosis type 1 (NF1). Surgical excision is the main treatment for localized disease; however, local recurrence (LR) remains high. Radiotherapy (RTx) is increasingly used to enhance local control in STS, but its use remains controversial due to the potential for increased major wound complications and an increased risk of secondary malignancies in NF1 patients. This study investigated the use and impact of RTx on local control in MPNSTs, particularly in the NF1 setting. Methods Surgically treated primary MPNSTs from 1988 to 2019 in the MONACO multicenter cohort were included. Differences in demographics, treatment, and RTx use between NF1 and non-NF1 cases were examined. Factors influencing RTx administration and LR were assessed via multivariable analyses. Results Among 499 patients (33.1% NF1), 143 (28.7%) experienced LRs. Radiotherapy was administered to 56.3% of patients (57.0% in the NF1 group), with 27.3% receiving neoadjuvant and 72.7% adjuvant RTx. RTx was administered significantly more often to high-grade and extremity tumors. While RTx did not affect overall survival, it reduced LR risk in sporadic cases (hazard ratio [HR] 0.530; 95% confidence interval [CI], 0.354–0.793) but not in the NF1 subgroup (HR 1.00; 95% CI, 0.545–1.85). In NF1 patients, a microscopically positive margin (R1) was the only risk factor for LR development (HR 2.1; 95% CI, 1.19–3.79). Conclusions RTx is frequently used in the treatment of MPNSTs, regardless of NF1 status. While it may affect the LR rate in sporadic cases, its impact on NF1 patients is less clear.

While hormonal changes have been recognised to influence seizure control and have been studied in association with menstrual cycles and pregnancy, there is a paucity of data on the menopause transition in epilepsy. Given the known effects of sex steroid hormones on neuronal excitability, their endogenous fluctuations during perimenopause, as well as menopause hormone treatments, may alter seizure control. Epilepsy may also be associated with premature ovarian insufficiency and early menopause. This is especially important for epilepsy-related comorbidities, for which menopause can constitute a second hit, such as osteoporosis. Additional considerations for females with epilepsy across the menopause continuum include changes in antiseizure medication clearance and potential interactions with menopausal hormone therapy or other concomitant medications. This comprehensive review summarises the currently available literature on epilepsy and menopause, highlights gaps in knowledge, and underscores the need for research efforts, particularly longitudinal studies investigating the menopause transition.