Citations

Abstract Background: Placebo response is crucial in interpreting treatment efficacy in ulcerative colitis (UC) trials. While it has been broadly studied, it remains underexplored in trials involving the growing number of biologics and small molecules for ulcerative colitis. Methods: We systematically searched PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL from inception to November 13, 2024. Eligible studies were induction-phase RCTs, including adult patients with moderate-to-severe UC who received a biologic and a small-molecule against a placebo. Primary outcomes were pooled clinical and endoscopic response and remission rates. Safety outcomes included adverse events (AEs), serious adverse events (SAEs), and withdrawal rates. Random-effect models were used for meta-analysis. Meta-regression identified predictors of placebo outcomes. Results: 26 induction RCTs with 3,937 placebo-treated patients were included. IL inhibitor trials had the highest placebo clinical response (36%) and endoscopic remission (21%), while JAK inhibitors had the lowest (21% and 2%). Overall placebo rates were 34% for clinical response, 8% for clinical remission, 19% for endoscopic response, and 11% for endoscopic remission. Adverse events occurred in 54%, SAEs in 8%, and withdrawals in 18%. Younger age and longer follow-up were linked to higher placebo responses; recent trials showed reduced endoscopic effects. Conclusion: These findings highlight the need to account for placebo variability in trial design and interpretation, particularly as biologic and small-molecule therapies continue to expand in UC treatment.

Background: Invasive and non-invasive neuromodulation in psychiatry represents a burgeoning field that leverages advanced neuromodulation techniques to address substance use disorders (SUDs). Aims: This narrative review synthesizes findings from multiple reviews to evaluate the efficacy of neuromodulation in treating SUDs. Methods: A comprehensive literature search was conducted between December 2024 and April 2025, focusing on systematic reviews and meta-analyses that examined various neuromodulation modalities, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). The selected reviews were analyzed to identify common themes, outcomes, and gaps in the current understanding of these treatments for SUDs. Results: 11 reviews met the final inclusion criteria; 5 focused on non-invasive neuromodulation (rTMS, tDCS) and 6 on invasive neuromodulation (DBS). Non-invasive neurostimulation was associated with modest improvements in craving and cognitive dysfunction in individuals with SUDs. Similarly, invasive neuromodulation (DBS), through high-frequency stimulation of the bilateral nucleus accumbens, appeared to reduce cravings and improve comorbid psychiatric symptoms in both preclinical and human studies. Importantly, small sample sizes, heterogeneity in targets and stimulation protocols, and short follow-up periods significantly limit the generalizability of current findings from both non-invasive and invasive neuromodulation studies. Conclusions: As novel and more effective therapies for the treatment of SUD are desperately needed, procedural interventional psychiatry holds promise. However, despite encouraging results, existing evidence is still preliminary, and larger, rigorously designed studies are warranted to further establish the safety and efficacy of neuromodulatory interventions for SUD treatment.

Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.

Study Design: A national prospective cervical spine surgery registry was developed to archive radiographic studies, patient-reported outcome measures (PROMs), and surgical implant data to assess long-term safety. Objective: To describe the design, development, funding, and implementation of a cervical spine data registry for 1000 patients with myelopathy and radiculopathy. Summary of Background Data: While surgery for cervical radiculopathy and myelopathy is safe and effective, there is significant practice variation among spine surgeons. While randomized clinical trials (RCTs) can provide high-quality comparative effectiveness data, RCTs lack the ability to evaluate the safety and effectiveness of various surgical procedures and implants among heterogenous real-world patient populations. The CSRS Registry was designed to collect patient demographics, outcomes, radiographic imaging, surgical approach, and implant data for the purpose of conducting high-quality research. Methods: Patients with cervical myelopathy or radiculopathy were enrolled in the CSRS National Registry. De-identified patient data, validated PROMs, radiographic data, and implant data were collected from multiple clinical sites across the United States. Results: One thousand patients [mean age, 58 y; 456 (46%) women] were enrolled, with 31% follow-up at 1 year. Five hundred ninety-two patients were diagnosed with radiculopathy, 252 with myelopathy, and 156 with radiculopathy and myelopathy. Patients had significant improvements in their PROMs after surgery. At 1 year, the mean NDI score improved from 37.2 to 20.9 ( P <0.001). The mean self-reported P-mJOA score at baseline was 14.2 and improved to 15.2 by 1 year ( P <0.001). Baseline CSDI score was 23.6 and improved with a 1-year decrease to an average score of 13.6 ( P <0.001). There was significant improvement in PROMIS-10 Physical Health score from 41.0 to 45.9 (n=311; P <0.001) at 1-year follow-up. Conclusions: The CSRS Registry has successfully collected clinical outcomes data that is being leveraged for comparative effectiveness research and evaluations of the long-term safety and effectiveness of spinal implants.

Abstract We conducted a post hoc analysis of data from Blood and Marrow Transplant Clinical Trials Network 1506 (MORPHO), a randomized trial of gilteritinib vs placebo as posttransplantation maintenance for patients with FLT3-ITD–mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 comutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD negative before HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC vs RIC. NPM1 comutation was associated with the largest magnitude of relapse-free survival benefit from post-HCT gilteritinib, and in these participants, post-HCT gilteritinib in the setting of RIC appeared to be as effective as MAC at preventing relapse. MAC appeared superior to RIC in preventing relapse only in participants who were NPM1 wild type at diagnosis and FLT3-ITD MRD positive before HCT. Our findings suggest that only a subset of patients with FLT3-ITD AML undergoing HCT may benefit from MAC and that, similar to AML therapy before HCT, the intensity of the HCT regimen should be adapted according to the molecular features of the disease. This trial was registered at www.clinicaltrials.gov as #NCT02997202.

OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is characterized by gait deterioration, cognitive disturbances, and urinary incontinence. Gait deficits pose safety hazards due to frequent falls, yet objective investigations of gait improvement following ventriculoperitoneal shunt (VPS) placement are limited. Therefore, the aim of this study was to assess objective improvement in gait parameters for patients with iNPH after VPS placement. METHODS All patients treated with a VPS for iNPH by the senior author at a single tertiary care center from December 2017 to January 2023 were retrospectively reviewed. Patients who underwent detailed motion analysis testing before surgery with > 1 follow-up assessment were included. Analyzed parameters included gait velocity, gait cadence, stride length, stride width, gait stability ratio, total support, and single support. Time-dependent linear mixed-effects models and generalized additive mixed-effects models (GAMMs) were used to model short-term and longitudinal gait parameter changes, respectively. RESULTS A total of 212 patients (137 male, median age was 75.2 years) who underwent VPS placement for iNPH were included, with a total of 747 gait analyses performed at a median last-gait analysis follow-up duration of 12.0 months. Statistically significant changes in all gait parameter values were seen between the preoperative time point and first postoperative follow-up (within 3 months) time point (paired Wilcoxon p < 0.001), with a statistically significant majority of patients experiencing improvement (binominal p < 0.0001). Longitudinal analyses using a GAMM showed increased gait velocity, single support, and stride length, with decreased stability ratio, step width, and total support at early time points, while a plateau was achieved around 6 months. CONCLUSIONS A detailed gait analysis demonstrated significant improvements in objective ambulation metrics, particularly in the gait velocity, stride length, and gait stability ratio, following VPS placement in patients with iNPH. Most patients maintained marked improvement from baseline to the last follow-up assessment, although a plateau of the benefit was experienced over longer follow-up.

Abstract Introduction Endogenous Cushing's syndrome (CS) is a rare endocrine disorder that chronically exposes patients to supraphysiological cortisol levels. Primary therapy for CS consists of surgery. Medical therapies are also considered for many patients with CS, including those who are not surgical candidates or have persistent or recurrent hypercortisolism after surgery. Osilodrostat, an adrenal steroidogenesis inhibitor, demonstrated sustained efficacy and safety in phase 3 clinical trials and is currently approved to treat endogenous CS in Europe and the United States. Because of limited clinical experience, questions remain about how to individualize osilodrostat treatment for different clinical scenarios and special populations. Additional guidance from experts based on clinical study and real-world experiences with osilodrostat is needed. Methods A modified Delphi consensus panel study was conducted consisting of 13 specialists from high-volume endocrinology centers with experience prescribing osilodrostat. Advisors participated in 3 consensus rounds (2 anonymous surveys, 1 virtual workshop) over approximately 10 months to provide guidance and recommendations on optimal osilodrostat use. Results Over 2 surveys and a 2-hour virtual workshop, 26 statements related to osilodrostat achieved consensus among Delphi panelists and 5 were excluded. Topics included patient preparation before osilodrostat initiation, baseline testing, dosing at onset and during treatment, managing dose adjustments, monitoring during dose titration, and treatment alterations for planned and unexpected clinical events. Conclusion Treatment guidance and recommendations for osilodrostat use were obtained using the Delphi method. These statements are intended to provide physicians with education and guidance on using osilodrostat to optimally treat patients with CS.

Lymphoscintigraphy, which is commonly used for sentinel lymph node mapping, can help diagnose lymphedema, lymphatic leakage, and lymphatic malformations and provides valuable information for surgical planning and treatment.