Citations

Objective Immune checkpoint inhibitor (ICI) myositis is a rare but a highly morbid condition, particularly with the ICI myositis triad syndrome of myositis, myocarditis, and myasthenia gravis. We report the clinical characteristics of ICI myositis and all‐cause mortality in these patients. Methods We performed a national retrospective cohort study of US veterans treated with an ICI between June 2011 and February 2022. Cases were identified by elevated creatinine kinase (CK) following ICI therapy and/or “myositis” in notes. Chart review determined if candidates had ICI‐associated myositis and were subsequently classified as isolated ICI myositis or ICI triad syndrome. Results Of 29,296 veterans treated with ICIs, 68 (0.2%) ICI‐induced myositis cases were identified, including 23 patients with ICI triad syndrome and 45 patients with isolated ICI myositis. Median survival duration for ICI triad syndrome was 2.5 (95% confidence interval [CI] 1.7–18.5) months in comparison to 20.4 (95% CI 6.2–60) months for isolated ICI myositis and 12.6 (95% CI 12.3–12.8) months median survival for patients treated with ICI without myositis. Patients with ICI triad syndrome had 60.0% mortality during the six months following initiation of ICI treatment, in comparison to 30.2% mortality in isolated ICI myositis and 31.5% mortality in patients without myositis. Six months after the first ICI treatment, subsequent mortality trends were similar in the three groups. Conclusion ICI triad syndrome is associated with higher overall mortality and shortened median survival times during the first six months after initial ICI therapy, whereas isolated ICI myositis is associated with similar mortality outcomes compared to patients treated with ICI who did not develop myositis. image

BACKGROUND: Despite the widespread adoption of minimally invasive surgery in the US, disparities in its use persist. One unexplored contributor is geographic access to robotic surgical systems. This study evaluates the geospatial association between: (1) Social Vulnerability Index (SVI) and open surgery rates, (2) availability of robotic systems and open surgery, and (3) open surgery rates in demographically similar areas with differing robotic access. STUDY DESIGN: Data from 6 sources were linked at the ZIP Code Tabulation Area (ZCTA) level to identify hospitals and to extract procedure modality, presence of robotic systems, and area characteristics. Regression analysis assessed the association between SVI and open surgery rates. Open rates were then compared between hospitals with and without robotic systems. Propensity score matching was used to compare open rates across matched ZCTAs by robotic access and SVI levels. RESULTS: Higher social vulnerability was associated with increased open surgery rates (estimate = 0.20; p < 0.01), with rates ranging from 18.3% in low-vulnerability areas to 32.7% in high-vulnerability areas. Among 3,446 eligible ZCTAs, 57% had at least 1 robotic system. ZCTAs without robotic systems had higher open surgery rates (42.9 vs 19.4 per 100 procedures; relative rate = 2.21; p < 0.01). This association remained significant after matching (relative rate = 1.66; p < 0.01), for the low-mid- and high-SVI strata, and 3 of the 5 procedures examined. CONCLUSIONS: When correcting for geographic variation, the availability of robotic surgery was associated with a decrease in open surgery rates.

ABSTRACT Background Sentinel lymph node (SLN) biopsy is a critical staging tool in skin and soft tissue cancers. Although technetium lymphoscintigraphy is the most common adjunct, indocyanine green (ICG) demonstrates a promising alternative in pediatric, adolescent, and young adult (AYA) skin and soft tissue cancers. Methods and Objectives Evaluate the safety and efficacy of ICG in SLN biopsy (SLNB) in diverse pediatric and AYA solid cancers in a multi‐institutional environment. This is a prospective, observational study conducted at 13 member institutions in the Pediatric Surgical Oncology Research Collaborative between 2019 and 2023. Eligible patients underwent SLNB for primary or recurrent solid skin and soft tissue tumors. Peritumoral ICG was administered intraoperatively. Outcomes included SLN detection rates, histopathology of excised specimens, and surgeon‐reported assessment of utility. Safety was assessed through adverse event reporting. Results Forty SLNB procedures yielded 84 specimens: 13 melanoma (32.5%), 12 squamous cell carcinoma (30%), 11 non‐rhabdomyosarcoma soft tissue sarcoma (27.5%), two rhabdomyosarcoma (5%), one Ewing sarcoma (2.5%), and one malignant peripheral nerve sheath tumor (2.5%). Histologic evaluation identified 81 lymph nodes, 75 benign (89.3%) and six malignant (7.1%); three specimens were adipose tissue (3.6%). Of 81 lymph nodes, 76% were ICG‐positive. ICG had a sensitivity of 79.5%, a specificity of 33%, and a positive predictive value of 96%. All malignant nodes were ICG‐avid. There were no adverse reactions to ICG at 30 days. Conclusions ICG is a safe and effective adjunct for SLNB in pediatric and AYA soft tissue and skin malignancies.

GGGGCC (G 4 C 2 ) repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Toxicity is thought to result from the accumulation of either repeat RNAs and/or dipeptide repeat proteins (DPRs) translated from repeat-containing transcripts through repeat-associated non-AUG (RAN) translation. To disentangle RNA from DPR toxicity, we mutated a CUG codon predominantly used to initiate DPR translation from all three reading frames. This mutation disrupted DPR synthesis while preserving the expression of repeat-containing RNAs. Despite the accumulation of RNA foci, behavioral deficits and pathological abnormalities, including p-TDP-43 inclusions, STING activation, motor neuron loss, neuroinflammation, and increased plasma neurofilament concentration, were alleviated in C9ORF72 mice. Base editing of the CUG codon also improved molecular phenotypes and survival in patient induced pluripotent stem cell–derived neurons, which highlights the potential of therapeutically targeting DPR production rather than repeat RNAs.

Background and Aims: Cholangiocarcinoma (CCA) is a rare but aggressive malignancy with poorly understood genetic susceptibility. To date, genome-wide association studies (GWAS) investigating germline variants associated with CCA risk remain limited. We aimed to identify genetic risk loci for CCA and its clinical subtypes through comprehensive GWAS and post-GWAS analyses. Approach and Results: We conducted a GWAS of 2366 CCA cases and 11,750 controls of European ancestry. Genome-wide significant loci ( p <5×10 −8 ) were identified and further examined through fine-mapping, functional annotation, and HLA imputation. Subgroup analyses were conducted by CCA subtypes and primary sclerosing cholangitis (PSC) status. Cross-trait linkage disequilibrium score regression and Mendelian randomization were employed to investigate the shared genetic architecture and potential causal relationships with a diverse range of traits. We identified 1 new genome-wide significant variant, rs535777 (OR=1.44), near HLA-DRB1/DQA1 associated with CCA, and 2 variants associated with extrahepatic CCA: rs116224263 (OR=0.17) in LINC02506 at 4p15.1 and rs6914950 (OR=1.63) near HLA-DRB1/DQB1 . Stratified analyses revealed rs2395184 (OR=3.51) near HLA-DRA/DRB5 associated with PSC-related CCA, and rs142674434 (OR=2.98) in THSD7A at 7p21.3 associated with non-PSC-related CCA. HLA imputation uncovered new amino acid residues associated with disease risk. Cross-trait analyses identified shared genetic signals between CCA and anthropometric, lipidemic, lifestyle, and medical traits. Mendelian randomization supported putative causal associations for 12 traits with CCA or its subtypes. Conclusions: Our large-scale GWAS highlights new genetic variants and HLA-linked mechanisms underlying CCA susceptibility. Integrating multi-step post-GWAS approaches enhances understanding of CCA pathogenesis and may facilitate the development of risk biomarkers for early detection and precision prevention strategies.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery is a popular intervention for small vestibular schwannomas in patients with preserved hearing. Gamma Knife radiosurgery (GKRS) and CyberKnife radiosurgery (CKRS) represent 2 alternative modalities, with CKRS potentially allowing for the delivery of higher doses over multiple sessions. However, the optimal dosing and hearing outcomes of CKRS remain unclear. This study systematically reviewed all literature describing outcomes following treatment of vestibular schwannomas with CKRS, with a focus on tumor control, hearing preservation, and dosing schema. METHODS: The PubMed, Scopus, and Embase databases were queried to identify primary retrospective studies reporting local tumor control and hearing preservation rates following CKRS for vestibular schwannoma. Studies were reviewed, and the systematic review and meta-analysis were performed according to PRISMA and meta-analysis guidelines. RESULTS: Fifteen studies with study periods ranging from 1998 to 2018 were included. These studies comprised 2018 patients (mean age, 60.2 years; range, 11-91 years; 52% female), of whom 64 had neurofibromatosis type 2. The mean follow-up was 40 (range, 6-120) months, and 309 patients had undergone prior treatment (surgery and/or stereotactic radiosurgery). In aggregate, local control at the last follow-up was 96% (95% CI, 95%-98%), and 73% (95% CI, 66%-81%) of patients had preserved hearing. The most common major complications after CKRS were facial neuropathy (1.4%), trigeminal neuralgia (1.3%), and hydrocephalus (0.5%). CKRS provides a high rate of short-term and mid-term tumor control with hearing preservation comparable with GKRS, but long-term outcomes remain under investigated. CONCLUSION: This systematic review and meta-analysis found that CKRS offers high rates of tumor control and hearing preservation in patients undergoing stereotactic radiosurgery for vestibular schwannomas. Current data suggest that CKRS is a reasonable, safe therapeutic option for patients with small tumors and preserved hearing. Further exploration in larger cohorts and direct comparison with GKRS is merited.

Objective: Auditory nerve monitoring through electrically evoked compound action potentials (eCAP) can be used to assess cochlear neural integrity during vestibular schwannoma (VS) resection. Herein, we report on 5 cochlear implant (CI) patients who underwent VS resection with present eCAP responses both intraoperatively and postoperatively. Patients either did not perceive any sound through their CI or rapidly adapted to electrical stimulation, suggesting that the presence of eCAP does not guarantee auditory nerve function in patients with VS resection. Patients: Five patients who underwent simultaneous VS translabyrinthine resection and cochlear implantation. Interventions: Simultaneous cochlear implantation and translabyrinthine microsurgical VS resection. Main outcome measure: Electrically evoked compound action potential. Results: All patients had eCAP responses present during their VS resection and for at least 50 days post-surgery. Three of the 5 patients did not perceive any sound with their cochlear implant. This shows that the presence of an eCAP alone does not guarantee a functional auditory nerve or auditory perception. The other 2 patients could hear non-speech sounds, but these sounds quickly became inaudible, indicating that their auditory nerve lacked the ability to integrate the electrical stimulus over time. Conclusions: The presence of an eCAP response does not guarantee auditory sensation through a CI. Although eCAP measurements provide insight into the function of the distal end of the nerve, it does not ascertain integrity or function of the larger auditory nerve pathway. Therefore, eCAPs should not be used in isolation to monitor auditory nerve function during VS resection.

Abstract Background Native vertebral osteomyelitis (NVO) is a life-threatening spinal infection with rising incidence and significant morbidity. Despite its growing burden, long-term data on clinical characteristics, management trends, and outcomes remain limited. Methods We conducted a 26-year multicenter retrospective cohort study of adults (≥18 years) diagnosed with NVO at Mayo Clinic sites between 1999 and 2024. Demographic, microbiologic, treatment, and outcome data were analyzed across five time periods. Predictors of treatment failure were assessed using a multivariable competing risk model. Results Among 1255 patients (median age 67; 66% male), lumbosacral involvement was most common (65%), and 21% had multilevel involvement. Pathogens were identified in 77%, most commonly Staphylococcus aureus (49%; Methicillin-susceptible S. aureus 37%, methicillin-resistant S. aureus 13%). Over time from 1999–2004 to 2020–2024, Gram-negative bacilli increased from 6% to 14% (P = .048). Comorbidities including chronic kidney disease (10% to 21%), active chemotherapy (6% to 11%), and immunosuppression (8% to 17%) increased significantly. Additionally, 1-year treatment failure declined (16% to 10%). In multivariable analysis, diabetes mellitus (subdistribution hazard ratio [sHR] 1.92, 95% CI 1.18–3.13) and multilevel involvement (sHR 1.67, 95% CI 1.17–2.38) were associated with increased incidence of treatment failure, while concurrent infections (sHR 0.57, 95% CI 0.37–0.87) and higher Charlson Comorbidity Index (sHR 0.62, 95% CI 0.43–0.90) were associated with lower failure. Conclusions This large multicenter cohort highlights increasing host complexity, shifting microbiology, and predictors of failure, emphasizing the importance of early risk stratification and tailored strategies, such as multidisciplinary evaluation and close follow-up of high-risk patients to improve outcomes.

Abstract Objectives Discuss the current status of advanced practice providers (APPs) onboarding to headache medicine (HM) practices in the United States and present recommendations of the American Headache Society (AHS) APP Work Group to improve the onboarding process. Background A high demand for care, national shortage of specialists, and multiple advancements in HM have led to an increasing interest and presence of APPs of various backgrounds in the field, currently without a unifying onboarding process. Efforts to standardize and optimize the onboarding process for APPs in HM practices are necessary, to ensure high standards in quality of care. Methods The APP Work Group of the AHS Practice Management Committee developed comprehensive recommendations through literature review, survey of AHS members, and expert consensus. A modified Delphi protocol was used to establish key onboarding goals, definitions, and best practice recommendations. Results Recommendations are made regarding duration of onboarding, appropriate supervision, formal education and procedural skills, scope of practice, grading and documentation of competence, and reciprocal feedback. Conclusion Currently, there are no standard onboarding and training guidelines for APPs in the field of HM. We provide recommendations for a more systematic approach to help develop qualified providers and enhance their retention in HM practices.