Citations

Abstract Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safety of treatment with pemigatinib, an oral, potent, selective FGFR1-3 inhibitor, in patients with advanced FGFR-altered CNS tumors. FIGHT-207 was a single-arm, open-label, phase 2 study of pemigatinib in patients with advanced solid tumors harboring FGFR fusions/rearrangements or other mutations. Patients received pemigatinib 13.5 mg once daily until disease progression or unacceptable toxicity. Endpoints included tumor response and safety. Of the 13 patients with CNS tumors in FIGHT-207, 10 had glioblastoma. Fibroblast growth factor receptor alterations were FGFR3-TACC3 fusions (n = 9), FGFR1 K656E mutations (n = 2), FGFR1 N546K mutation (n = 1), and FGFR1-MITF fusion (n = 1). Three patients (23%) displayed objective responses (1 complete, 2 partial). Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors.

Background: Femoroacetabular impingement (FAI) is a common cause of hip pain in female athletes. There are limited data on midterm outcomes for female athletes undergoing hip arthroscopic surgery. Purpose: To evaluate return-to-sport rates and clinical outcomes in female athletes with FAI after primary hip arthroscopic surgery with labral repair and femoral osteochondroplasty. Study Design: Case series; Level of evidence, 4. Methods: A retrospective analysis of a single institution’s database was performed to identify female athletes who underwent primary hip arthroscopic surgery with labral repair and femoral osteochondroplasty from July 2011 to October 2019 with a minimum 5-year follow-up. Preoperative radiographs were evaluated for the lateral center-edge angle, Tonnis angle, Tonnis grade, and alpha angle. Patient-reported outcome measure (PROM) scores, including those for the modified Harris Hip Score, Hip Outcome Score, Tegner Activity Scale, and visual analog scale for pain, as well as patient satisfaction with surgery were analyzed postoperatively. Results: A total of 63 hips (27 left, 36 right) in 56 female patients (mean age, 21.6 ± 8.0 years; mean body mass index, 24.7 ± 4.8 kg/m 2 ) were included and followed for a mean of 8.4 ± 2.1 years (range, 5.0-13.2 years). Preoperatively, patients participated in basketball (n = 18), dance (n = 21), hockey (n = 8), and soccer (n = 12). Of the 56 patients, 41 attempted to return to sport. There were 28 (68%) female athletes who successfully returned to their preoperative sport. Of the total cohort, 21 (38%) patients cited non–hip-related factors for discontinuing their sport. All postoperative PROM scores improved significantly compared with preoperatively ( P ≤ .002) for patients with available preoperative data. Those who returned to sport had significantly improved Hip Outcome Score values compared with those who did not return to sport ( P ≤ .010). Conclusion: Female athletes who underwent primary hip arthroscopic surgery for FAI had significant improvements in PROM scores and moderate return-to-sport rates at a minimum 5-year follow-up. Most athletes discontinued sports because of non–hip-related factors, although hip-related issues were also cited. Our analysis highlights the need for thorough perioperative counseling and establishing appropriate patient expectations for female athletes before hip arthroscopic surgery.

Abstract Objectives/Background This study was undertaken to review the published literature and provide a position statement from the American Headache Society regarding the safety, efficacy, and impact on access to care of telemedicine for the clinical management of patients with headache disorders. Access to specialized care in headache medicine is severely limited in the United States and worldwide. Telemedicine has been used as an approach to care delivery in headache medicine for more than a decade, with accelerated adoption during the COVID‐19 pandemic. There is now uncertainty regarding the extent to which telemedicine will be accepted by health systems and reimbursed by payers moving forward. The purpose of this position statement is to summarize evidence and clinical experience supporting the utility of telemedicine in headache medicine. Methods Evidence regarding the safety and efficacy of telemedicine, and patient and clinician satisfaction with the use of telemedicine for headache specialty care, was gathered from a variety of sources, including PubMed, Google Scholar, and ClinicalTrials.gov . The results and conclusions based upon these results were reviewed and discussed by the authors and the Board of Directors of the American Headache Society to confirm consistency with clinical experience and to achieve consensus. Results Several randomized clinical trials and observational studies have been performed to compare telemedicine with in‐person visits in the management of patients with headache disorders. These studies showed consistently that telemedicine is noninferior to in‐person care based upon multiple outcome measures, including disability measures, patient satisfaction, and clinician satisfaction. In addition, these studies found that telemedicine rarely leads to a missed diagnosis of secondary headache or mismanagement of primary headache. Telemedicine has substantial advantages for patients, including improved access to care and reduced costs associated with obtaining care. Studies evaluating health care utilization indicate no significant differences between patients evaluated and treated virtually versus in person. Obvious limitations of telemedicine include the inability to perform an in‐person physical exam or to perform injections. For a substantial number of patients, however, these limitations are outweighed by its advantages. The experience with telemedicine reported in the literature is consistent with the experience of the Board of Directors of the American Headache Society, who endorse its use for patients when feasible and appropriate. Conclusion Telemedicine has significantly advanced the care of patients with headache disorders. Its further development and deployment should be supported and reimbursed.

ABSTRACT Background Advanced therapies increase the risk of shingles in inflammatory bowel diseases (IBD). Aim To compare the risk of shingles with different advanced therapies in patients with IBD. Methods We identified patients with IBD who initiated treatment with tumour necrosis factor (TNF) antagonists, anti‐integrins, anti‐interleukins, Janus kinase (JAK) inhibitors, or sphingosine‐1 phosphate receptor (S1PR) modulators between 2016 and 2022 and had follow‐up for at least 1 year before and after treatment initiation. We estimated the incidence rate (IR per 100 person‐year [PY]) of shingles (overall and complicated) and compared the risk with different advanced therapies through multinomial propensity score‐based inverse probability of treatment weighting (IPTW), with propensity scores estimated through generalised boosted models, accounting for disease characteristics, healthcare utilisation, comorbidities and prior and concomitant medications. Weighted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for multiple treatment comparisons. Results We included 21,675 patients followed over 27 months. IRs per 100 PY of shingles and complicated shingles were: TNF antagonists 1.0/0.3, anti‐integrin agents 1.4/0.4, anti‐interleukins 1.2/0.5, JAK inhibitors 3.3/0.9 and S1PR modulators 2.0/1.0. After adjusting for confounding variables, JAK inhibitors were associated with higher risks of shingles than TNF antagonists (HR 2.19; 1.28–3.75), anti‐integrins (HR 1.87; 1.12–3.14) and anti‐interleukins (HR 1.70; 0.98–2.96). Conclusions JAK inhibitors were associated with 1.7–2.2‐fold higher risk of shingles than other advanced therapies.

ABSTRACT Introduction and Objectives Female urethral strictures remain a challenging clinical entity with limited data on optimal reconstructive techniques. This study presents 12‐month clinical and patient‐reported outcomes following a novel transurethral approach to dorsal inlay buccal graft urethroplasty. Methods We evaluate the outcomes of consecutive female patients with urethral strictures treated via dorsal inlay buccal graft urethroplasty from October 2021 to November 2024. Preoperative evaluation included cystoscopy, uroflowmetry, and/or voiding cystourethrogram. Follow‐up at 4 and 12 months included cystoscopy, uroflowmetry, and patient‐reported outcomes measured via the Global Response Assessment. Success was defined as absence of recurrence on cystourethroscopy. Results Twenty‐one patients were included in the study, with 95% having undergone prior treatments (90% dilation/DVIU and 9% urethroplasty). Stricture locations varied across the distal (33%), mid (19%), proximal (19%), and multifocal/pan urethral (19%). The median operative duration was 60 min (IQR: 56–86) and all were discharged on the day of surgery. Nineteen patients (90%) underwent a dorsal inlay procedure, while two (10%) required combined dorsal and ventral inlay due to obliterative stricture. No complications were observed. The median follow‐up was 13.2 (IQR: 5.1–23.5) months, during which time 1 patient underwent retreatment for recurrent stricture. Clinical success was 95% at 4 months and 92% at 12 months. Median peak urinary flow rate preoperatively versus 4‐month postoperatively was 7.0 cc/s versus 13.0 cc/s ( p = 0.20) and at 12‐month postoperatively was 13.3 cc/s ( p = 0.50). 90% of patients reported improvement on the Global Response Assessment. There were no cases of de novo stress urinary incontinence. Conclusions This novel transurethral dorsal inlay buccal graft urethroplasty offers a safe and efficient treatment for female urethral strictures with durable clinical and patient‐reported outcomes at 12 months. The technique's minimal urethral mobilization translates into shorter operative times and a low risk of stress incontinence, making it a promising alternative to traditional approaches.

Abstract Our inability to obtain nerve samples from the vast majority of neuropathic pain patients impedes our ability to understand the disease, creates challenges in understanding mechanisms in specific patient populations, and limits our ability to make treatment decisions based on quantifiable molecular data. Fields like oncology have overcome these problems to take advantage of the insight that sequencing offers for understanding mechanisms of disease and have leveraged these molecular insights to dramatically change the treatment landscape in the past decade. Here we tested the hypothesis that skin biopsies could be used to gain insight into neuronal transcriptomic changes in patients with paclitaxel-induced peripheral neuropathy (PIPN). Our analysis reveals that hundreds of differentially expressed genes (DEGs) found through bulk RNA sequencing in these skin biopsies are likely contributed by dorsal root ganglion (DRG) neuronal axons and/or terminals. Up-regulated genes were representative of broad class of nociceptors whereas down-regulated genes were associated with putative injured DRG neurons expressing the PDIA2 gene. DEGs that could be confidently associated with specific subsets of skin cells were mostly expressed by keratinocytes supporting a growing literature tying keratinocyte-neuron communication abnormalities to pain in PIPN. We validated these findings by analyzing additional previously published datasets and through prospectively conducted spatial transcriptomics experiments on human skin biopsies. Our findings warrant further assessment of skin biopsies in additional neuropathic pain populations to gain insight into DRG neuron changes that have previously been thought to be inaccessible in routine clinical or scientific assessments in most patients.