Citations

This manuscript summarizes the first part of the proceedings of the 2023 Dublin ISUP Consensus Conference encompassing the best practice recommendations on the pathology of neoplasms of urachal origin. The rationale for convening this consensus conference was the lack of structured and consented histopathologic recommendations in these rare tumors. Consensus among the meeting participants (n=80) was reached on the following statements: (1) combination of gross, histologic, clinical and imaging findings with exclusion of secondary tumor metastasis are to be used in the diagnosis of urachal carcinoma; (2) the 2022 World Health Organization (WHO) separate criteria for the diagnosis of urachal adenocarcinoma and for nonglandular carcinoma should be applied; (3) specific elements are to be evaluated and recorded in the gross examination of resection specimens containing urachal tumors; (4) sampling considerations for resection specimens containing urachal tumors are advised; (5) participants are against using 5% or 10% cutoff for the extent of intraepithelial carcinoma in urachal mucinous cystic tumor of low malignant potential; (6) use of immunohistochemical markers for the differential diagnosis of urachal adenocarcinomas in transurethral resection (TUR) specimen is considered optional; (7) similar tumor classificatory (nosology) rules for carcinomas arising from bladder mucosa (eg, urothelial carcinoma, squamous cell carcinoma, and neuroendocrine carcinoma) should be applied for nonglandular urachal carcinomas; (8) a new staging approach other than the previously proposed systems should be designed for urachal carcinoma; (9) a system modifying the current Tumor-Node-Metastasis (TNM)/American Joint Committee on Cancer (AJCC) staging system for urinary bladder cancer is considered appropriate for a study in urachal carcinoma; and (10) several histologic elements are to be reported when diagnosing urachal carcinoma in TUR and resection specimens. This report from the Dublin ISUP consensus conference will serve as a practice recommendation for pathologists and as a guide for future standardized reporting protocols and research regarding urachal tumors. In addition, an international database for urachal cancers under the guidance of ISUP is being planned to be established to address pertinent issues in the pathology of urachal cancers.

Barriers to incorporating pharmacogenetics into routine clinical practice in the United States are well documented. Initial surveys by the Clinical Pharmacogenetics Implementation Consortium (CPIC) in 2009 and 2010 identified barriers across four key domains that have hindered the widespread adoption of clinical pharmacogenetic testing. These are presented verbatim as: (i) absence of a definition of the processes required to interpret genotype information and to translate genetic information into clinical actions; (ii) need for recommended drug/gene pairs to implement clinically now; (iii) clinician resistance to consider pharmacogenetic information at the bedside; and (iv) concerns about test costs and reimbursement. Over time, many of these challenges have been overcome, and clinical pharmacogenetic testing has subsequently reached broader implementation. Despite this progress, several barriers remain that block further adoption. This narrative review used authors' expertise and experience to identify and describe current barriers to pharmacogenetic implementation across seven domains in the United States: equity and inclusion; guidelines and supporting evidence; regulatory agency oversight; payer coverage and insurance; availability of quality pharmacogenetic tests; electronic health records; and provider and patient education. Within each domain, it revisits past successes and challenges and explores remaining barriers. We also propose solutions to address ongoing challenges across these domains, including further expansion of recommendations beyond pharmacogenetic‐specific guidelines, standards for designing clinical decision support tools, and broader pharmacogenetics education. Addressing these remaining obstacles directs work to enable broader adoption of clinical pharmacogenetic implementation to ultimately improve patient outcomes.

Objective To assess integration of a single-use robotic-assisted cochlear implant (RA-CI) electrode array insertion system into surgical workflows, identify potential challenges, and inform best practices. Study Design Survey. Setting Survey data from 16 surgeons across 10 US hospitals. Patients CI candidates 12 years and older with radiographically normal cochleae. Intervention CI surgery with single-use RA-CI insertion system during electrode array insertion. Main Outcome Measures Number of RA-CI to achieve proficiency, estimated additional time for RA-CI, and best practices to successfully incorporate the RA insertion system into CI surgery. Results A total of 121 RA-CI cases were performed. All surgeons completed the survey. Most surgeons (62.5%) reported they would feel comfortable using the device within five cases. Eight (50%) reported use of the RA system added 5 to 10 minutes to the case, and seven (44%) reported an added 10–15 minutes. Providing adequate incision size to secure the unit base superior to the temporal line and maximizing exposure of the facial recess were the most recommended best practices. Additional recommendations included pulling the receiver/stimulator forward within the pocket to facilitate a full electrode array insertion and considering drive head placement and mastoidectomy size to maximize overall visibility during electrode array insertion. Conclusions Proficiency with an RA electrode array insertion system during CI surgery can be achieved with minor adjustments to the surgical approach, within relatively few use cases (generally <5) and with minimal time addition (between 5 and 15 min). Training to specific best practices is important before initial clinical use.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

ABSTRACTIntroduction and ObjectiveProcedural therapies for overactive bladder (OAB) most often include intradetrusor onabotulinumtoxinA (BTX) injections, sacral neuromodulation (SNM), and percutaneous tibial nerve stimulation (PTNS). Despite their proven efficacy, real‐world data on therapy continuation and crossover rates between these modalities remain limited. This study aimed to evaluate longitudinal patterns of treatment continuation and therapy crossover among women receiving procedural OAB treatments.MethodsWe conducted a multi‐institutional retrospective cohort study of women with idiopathic OAB who underwent index BTX, SNM, or PTNS between 2014 and 2022. Patients were identified using electronic medical records, and follow‐up data were collected through December 31, 2023. The primary outcomes included duration of maintenance treatments and crossover to another procedural therapy for OAB. Kaplan–Meier survival analysis estimated rates of continued treatment, and a log‐rank test assessed differences in crossover rates among treatment groups.ResultsA total of 506 women met inclusion criteria: 266 (52.6%) received BTX, 114 (22.5%) underwent SNM, and 126 (24.9%) received PTNS. Ongoing treatment rates were lowest for PTNS, with only 17.1% maintaining therapy between 3 and 5 years and 26.1% crossing over to another procedure within 3 years. Among BTX patients, 65.2% underwent repeat treatment within 3 years, and 9.5% of patients crossed over to another procedure within 3 years. Of those with 5 or more years of follow‐up, 39.1% of patients continued with BTX procedures in the 3–5‐year follow‐up timeframe. Among SNM patients, the cumulative revision rates were 7.6% at 1 year and 10.9% at 2 years. 13.1% of patients crossed over from SNM to another procedure within 3 years (the vast majority to BTX).ConclusionsPTNS had the lowest ongoing therapy rates and the highest crossover rates. BTX and SNM demonstrated similar crossover rates. These findings underscore the importance of individualized patient counseling and treatment selection based on expectations of therapy persistence. Future research should focus on optimizing patient selection, improving long‐term adherence strategies, and evaluating novel or combined therapeutic approaches for OAB management.

Abstract Accurate prediction of risk of progression from smoldering (SMM) to active multiple myeloma (MM) is paramount to individualized early therapeutic strategies with minimum risk of overtreatment. Current risk stratification models do not account for evolving biomarker trajectories. We assembled the largest cohort to date of 2,270 SMM patients from six international centers with longitudinal clinical and biological data to train and validate the PANGEA 2.0 risk models. Four evolving biomarkers were significantly associated with shorter time-to-progression: M-protein increase ≥0.2g/dL, involved:uninvolved serum free light chain ratio increase ≥20, creatinine increase >25%, and hemoglobin decrease ≥1.5g/dL. PANGEA 2.0 outperforms established models including the 20/2/20 and IMWG models by more accurately predicting progression (C-statistics=0.69–0.84), even without biomarker history (C-statistics=0.69–0.83) or recent bone marrow biopsy. PANGEA 2.0 is an easy-to-use, open-access tool (https://ghobrial.shinyapps.io/pangea_2_calculator) to improve and individualize SMM risk stratification. Validation tools are available to compare PANGEA 2.0 to established models (https://ghobrial.shinyapps.io/pangea_validation).

Abstract Background: mTOR activation is associated with chronic inflammation in ME/CFS. Previous studies have shown that sustained mTOR activation can cause chronic muscle fatigue by inhibiting ATG13-mediated autophagy. This highlights the pivotal role of mTOR in the pathogenesis of ME/CFS. Methods: We conducted a decentralized, uncontrolled trial of rapamycin in 86 patients with ME/CFS to evaluate its safety and efficacy. Low-dose rapamycin (6 mg/week) was administered, and core ME/CFS symptoms were assessed on days 30 (T1), 60 (T2), and 90 (T3). Plasma levels of autophagy metabolites, such as pSer258-ATG13 and BECLIN-1, were measured and correlated with clinical outcomes, specifically MFI. Results: Rapamycin (6 mg/week) was tolerated without any SAEs. Of the 40 patients, 29 (72.5%) showed strong recovery in PEM, fatigue, and OI, along with improvements in MFI fatigue domains and SF-36 aspects. High levels of BECLIN-1 were detected in T3. Plasma pSer258-ATG13 levels were strongly downregulated at T1. Spearman’s correlation analysis indicated an association between autophagy impairment and reduced activity. Conclusions: Low-dose rapamycin effectively reduced PEM and other key symptoms in patients with ME/CFS, as measured by BAS, SSS, MFI, and SF-36. Future studies should encompass dose optimization and develop a diagnostic tool to identify responders with mTOR-mediated autophagy disruption.

Background: Supracondylar humerus fractures (SCH) are the most common type of elbow fracture in children, with many cases requiring surgery. Treatment of postoperative pain for SCH has high variability, but can often be treated effectively with minimal or no opioids. Furthermore, there is significant morbidity related to pediatric opioid consumption. The goal of this study was to characterize prescription patterns in the United States following closed reduction and percutaneous pinning (CRPP) of SCH. Methods: All patients aged 10 or younger years who underwent CRPP of SCH from January 2010 to December 2021 were identified in the PearlDiver Mariner Claims Database. The primary outcome was postoperative pain medication prescriptions in the 30 days following SCH CRPP. Patient demographics, prescription duration, and morphine milligram equivalents (MME) were analyzed. Multivariable-log-binomial mixed regression models were constructed to assess factors associated with increased opioid prescription. Results: In total, 43,611 SCH CRPP cases in patients aged 10 or younger were identified from 2010 to 2021. Throughout the study period, 48.6% of patients (21,191/43,611) received and filled a narcotic pain prescription. The percentage of patients receiving opioid medication decreased from 54.7% in 2010 to 27.4% in 2021. Opioid prescriptions totaled a mean of 6.1±2.1 days of narcotics with a mean of 79.2 MME prescribed per patient. Increased patient age, increased Elixhauser comorbidity index, and Medicaid insurance were all associated with increased opioid prescription (P<0.001). Living in the Northeast, increased family income, and commercial insurance were associated with decreased opioid prescriptions (P<0.001). Conclusions: Nearly half of the patients over the past decade treated with CRPP for SCH received a narcotic prescription. However, there has been a steady decline in the proportion of patients being prescribed opioids, with only 27.4% receiving opioids in 2021. Further, patients with increased comorbidities or those insured by Medicaid with lower mean family income may be at risk for increased opioid prescription. While efforts have been made to reduce opioid overprescribing, there continues to be room for further reduction in opioid utilization after CRPP for SCH moving forward.