Sevasemten (EDG-5506) is an orally administered, investigational small molecule that selectively modulates fast muscle fibre contraction by inhibiting fast myosin ATPase. In animal models of Duchenne and Becker muscular dystrophy (DMD and BMD, respectively), sevasemten reduced the muscle contraction injury that leads to inflammation, fibrosis and muscle loss without affecting function. The aim of this study was to evaluate the long-term safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics of sevasemten in adult participants with BMD who had already experienced a decline in function and would be anticipated to continue to decline based on natural history. This open-label, dose escalation, phase 1 b study (NCT05160415) was conducted at a single site and enrolled ambulatory adults with BMD aged 18-55 years; the study is completed. Eligible participants received 10 mg of sevasemten once daily (QD) for 8 weeks, followed by 15 mg QD for 4 months, 20 mg QD for 9 months, and 10 mg QD for 9 months. The primary objective was to assess the safety and tolerability of sevasemten in adults with BMD; endpoints included adverse events (AEs), PK, change from baseline in circulating biomarkers of muscle injury, as well as physical function measures. The study enrolled 12 adults with BMD. Sevasemten was well tolerated; all AEs were mild or moderate in severity and there were no serious AEs or AEs leading to discontinuation. Treatment with sevasemten was associated with reductions in circulating biomarkers of muscle injury that were evident within 4 weeks and sustained for up to 24 months. Physical function, as assessed by North Star Ambulatory Assessment (NSAA), was stable over 24 months. Sevasemten treatment for up to 24 months in adults with BMD was well tolerated and associated with durable reductions in muscle injury biomarkers, consistent with preclinical studies and near maximal with the 10 mg dose, as well as functional stabilisation. Further clinical development is ongoing. Edgewise Therapeutics, Inc.
Lumbar disc herniation (LDH) is rare in juveniles and may present atypically, potentially delaying referral for neurosurgical evaluation. We aimed to assess diagnostic and treatment delays and to evaluate short-term surgical outcomes in pediatric patients undergoing microdiscectomy for LDH at our department over a 10-year period. We retrospectively reviewed consecutive patients under 18 years of age who underwent microdiscectomy for LDH at our institution between 2015 and 2025. Clinical presentation, timing of imaging and surgery, and postoperative outcomes were analyzed. Twenty-one patients were included (mean age 14.6 ± 2.1 years, 57% females). Median body mass index (BMI) was 21.2 (range 18.7-36.9). All patients presented with low back pain, and 92.5% had radicular symptoms. The median time from symptom onset to MRI was 6 months (range 0-12 months), and to surgery 12 months (range 0-36 months). Most patients (90.5%) were operated at one level; L4/L5 and L5/S1 were the most commonly affected levels. At 3 months after surgery, 95.2% of patients reported improvement of back pain, while all patients experienced relief of radicular symptoms. In our cohort of pediatric patients with LDH, short-term outcomes following microdiscectomy were generally favorable despite substantial delays in diagnosis and referral for surgical treatment. These findings may suggest that, unlike in adults, prolonged symptom duration does not necessarily compromise recovery in children, although this should be interpreted with caution given the limited sample size and follow-up period. Nevertheless, increased awareness of pediatric LDH could facilitate earlier neurosurgical evaluation, streamline care pathways, and potentially further optimize patient management.
Although survival after major burn injury is increasingly common, persistent psychosocial morbidity often remains prevalent, and the relationship between burn severity and long-term psychosocial recovery is less understood. We aimed to evaluate longitudinal trajectories of mental health and social recovery across large burn-size strata to examine whether injury severity differentially influences internal psychological outcomes versus external social participation. We conducted a retrospective, multicenter longitudinal analysis of adults with ≥20% total body surface area burns enrolled in the Burn Model System National Longitudinal Database, using outcome measures available across their respective collection periods. Participants were stratified by total body surface area groups of large (20-49.9%), very large (50-69.9%), or massive (≥70%). Outcomes included Patient-Reported Outcomes Measurement Information System domains of Depression, Anxiety, and Ability to Participate in Social Roles; Community Integration Questionnaire-Social Integration; and employment status assessed at 6-, 12-, and 24-months post-injury. Mixed-effects linear regression models adjusted for demographic and clinical covariables. Among 815 participants, depression and anxiety remained elevated relative to population norms, while social participation improved across all burn sizes longitudinally. Survivors with massive burns demonstrated the greatest improvement in mental health over 24-months, with changes reaching clinically meaningful magnitude, and their community integration at 24-months was comparatively preserved, coming closest to pre-injury burn levels despite lower perceived social role ability and employment. These findings demonstrate that psychosocial recovery over the first 24-months does not worsen in proportion to injury severity, indicating that injury severity alone should not define prognosis. Rather, survival and rehabilitation after massive burn injury can translate into meaningful psychological adaptation and social integration that benefits from sustained, multidisciplinary follow-up across all burn severities.
Study DesignRetrospective cohort study.ObjectivesTo examine the impact of non-tobacco nicotine (NTN) dependence on pseudarthrosis and postoperative complications following posterior cervical fusion (PCF).MethodsThe TriNetX national database was queried for adult patients (18-80 years) who underwent a primary posterior cervical fusion (2012-2025). Patients were stratified into 3 cohorts: non-tobacco nicotine-dependent (NTND) patients, tobacco-dependent (TD) patients, and non-dependent controls. Patients underwent propensity-score matching, and pairwise comparisons (NTND vs control, TD vs control, NTND vs TD) were performed. The primary outcome was pseudarthrosis development, and secondary outcomes included medical/surgical complications.ResultsA total of 7102 patients were included. At 3 years, NTND patients had higher rates of pseudarthrosis (2.51% vs 1.84%, P = 0.019) compared to matched controls. Compared to controls at 3 months and 3 years, NTND was associated with significantly higher risks of all other postoperative complications (P < 0.05) except DVT. Compared to controls, TD patients had higher rates of all postoperative complications at 3 months and 3 years, except pseudarthrosis (P < 0.05). Compared to TD patients, NTND patients had higher rates of cervical fracture and pneumonia at 3 months (P < 0.05), and higher rates of cervical fracture at 3 years (P < 0.05). At 3 months, the NTND cohort demonstrated lower rates of opioid abuse/dependence, readmission, and emergency service use (P < 0.05).ConclusionsNon-tobacco nicotine dependence is associated with risk of perioperative and long-term complications following posterior cervical fusion compared to control patients, yet is not significantly different from TD patients. Providers may consider this data during preoperative counseling and surgical optimization.Level of EvidenceIII.
Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non-small cell lung cancer (NSCLC) who have disease progression after prior EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options, creating a need for more effective subsequent therapies. To provide final overall results of a trial assessing whether adding ivonescimab (a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor) to chemotherapy improves overall survival in this population. Randomized, double-blind, placebo-controlled phase 3 trial conducted at 55 sites in China. From January 25 to November 2, 2022, a total of 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025. Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n = 161) or placebo (n = 161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy. This final results report focuses on overall survival, the key secondary end point, tested in a hierarchical manner (the primary end point was progression-free survival assessed by an independent radiology review committee). The 322 enrolled patients had a median age of 59.4 years, and 51.6% were female. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved overall survival compared with chemotherapy alone (median survival, 16.8 months vs 14.1 months; stratified hazard ratio, 0.74; 95% CI, 0.58-0.95; P = .02). The absolute difference in median overall survival was 2.7 months. Estimated 30-month survival rates were 29.1% (95% CI, 22.1%-36.4%) with ivonescimab and 18.4% (95% CI, 12.8%-24.8%) with placebo. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively. Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy. ClinicalTrials.gov Identifier: NCT05184712.
Advanced head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, particularly in resource-limited settings with restricted access to targeted or immune therapies. We evaluated whether adding triple oral metronomic chemotherapy (OMCT; erlotinib, celecoxib, methotrexate) to paclitaxel-carboplatin (PC) improves overall survival (OS) in patients with platinum-sensitive, unresectable advanced HNSCC. This was a single-center, investigator-initiated, prospective, randomized, open-label, phase III superiority trial conducted at a tertiary cancer center in North India. A total of 238 adults with histologically confirmed, unresectable advanced HNSCC eligible for palliative platinum-based chemotherapy were randomly assigned 1:1 after stratification by tumor site and Eastern Cooperative Oncology Group (ECOG) performance status. Arm A received PC plus OMCT; Arm B received PC alone. The primary end point was OS. Secondary end points included progression-free survival (PFS), quality of life (QoL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Functional Assessment of Cancer Therapy-Head & Neck), and safety. Among 238 patients (119 per arm), the median age was 47 years; 97.8% were male, and 78% had ECOG performance status (PS) 0-1. The median OS was 10 months (95% CI, 8.3 to 11.7) with PC + OMCT versus 5 months (95% CI, 3.9 to 6.1) with PC alone (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72]; P < .001). The median PFS was 6 months versus 2 months, respectively (HR, 0.38 [95% CI, 0.28 to 0.50]; P < .001). QoL analyses demonstrated clinically meaningful preservation across multiple domains in the PC + OMCT arm. Grade ≥3 toxicities did not increase with the addition of OMCT. In platinum-sensitive advanced HNSCC, the addition of triple OMCT to PC significantly improved OS and PFS with acceptable toxicity. PC + OMCT represents a feasible and cost-conscious first-line option in resource-constrained settings.
Introduction:Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, humoral and cellular immunodeficiency, sensitivity to ionizing radiation, and a tendency to malignancy. The aim of this study was to evaluate the demographic characteristics, immunodeficiency status, laboratory findings, and prognosis of children with AT based on a single-center experience.Patients and Methods:Nineteen pediatric patients diagnosed with AT between 2003 and 2024 were retrospectively analyzed at a single tertiary center.Results:The study included 11 male and 8 female patients, with a mean follow-up duration of 72.6 ± 41.3 months. The mean ages at symptom onset and diagnosis were 30.47 ± 23.7 months and 82.32 ± 26.5 months, respectively. The most common presenting symptoms were gait instability, ocular telangiectasia, and recurrent respiratory tract infections. Immunological evaluation revealed IgA deficiency in 57.9% of the patients and IgG deficiency in 15.8%. A hyper-IgM AT phenotype was identified in two patients (10.5%). During follow-up, bronchiectasis and hepatosteatosis developed in 26.3% of the patients. One patient (5.2%) developed type 2 diabetes mellitus, and malignancy occurred in three patients (15.7%). Overall, 6 patients (31.5%) died during the follow-up period.Conclusion:Ataxia-telangiectasia is a rare multisystem disorder associated with significant morbidity and mortality. Early diagnosis, comprehensive multidisciplinary follow-up, regular malignancy surveillance, and preventive strategies for recurrent sinopulmonary infections are essential for improving clinical outcomes and prognosis in affected patients.
Purine nucleoside analogues are highly effective in the treatment of hairy cell leukemia (HCL) but are associated with myelosuppression and immunosuppression. Targeted therapy with the BRAF inhibitor vemurafenib in combination with the anti-CD20 antibody rituximab has shown marked efficacy, but traditional dosing of vemurafenib (960 mg twice daily) requires frequent dose reductions. We conducted a prospective observational study of low-dose vemurafenib (240 mg twice daily orally for 8 weeks) plus rituximab (375 mg/m² intravenously every 2 weeks for 14 weeks, 8 total doses) in adults with treatment-naïve or relapsed/refractory HCL. Fifteen patients were enrolled. All achieved complete hematologic recovery, with normalization of thrombocytopenia (>100 ×10³/µL) and neutropenia (>1.0 ×10³/µL) by a median of 15 and 29 days, respectively. The overall response rate was 87%, including 11 complete responses (73%; 95% CI, 48-89%) and 2 partial responses, with 8 patients (53%; 95% CI: 27-79%) achieving MRD negativity at 6 months. Front-line patients (n=7) had 6 CRs (86%; 95% CI: 42-100%) and 4 were MRD-negative (57%; 95% CI: 18-90%), while relapsed/refractory patients (n=8; median of 1 prior therapy) had 5 CRs (63%; 95% CI: 24-91%) and 4 were MRD-negative (50%; 95% CI: 16-84%). At a median follow-up of 18 months, one patient progressed at 20 months; median progression-free survival was not reached. No grade 3-4 toxicities or deaths occurred. Low-dose vemurafenib combined with rituximab induced rapid hematologic recovery, and favorable tolerability in patients with both untreated and relapsed/refractory HCL. NCT05388123.
This study aimed to evaluate the efficacy of robot-assisted reconstruction using end-to-side ureteroureterostomy (UU) and Lich‒Gregoir ureterovesical reimplantation (UR) for complicated duplex kidneys in children. A retrospective study was conducted on pediatric patients who underwent combined robotic UU and Lich‒Gregoir UR between January 1, 2021, and January 1, 2024. The inclusion criterion was the presence of concurrent upper- and lower-pole ureteral pathologies. Surgical time, postoperative length of stay, pre- and postoperative anteroposterior diameter of the renal pelvis (APD), ureteral diameter (UD), renal function (RF) of the affected kidney, and complications were analyzed. In total, 12 patients presented with urinary tract infections (UTI, n = 9), incontinence (n = 2), and abdominal pain (n = 1). Upper-pole pathologies included ectopic ureters (10 cases) and ureteroceles (2 cases). Lower-pole pathologies comprised ureteral stricture (n = 4) and vesicoureteral reflux (VUR, n = 8). The median surgical time was 177.5 minutes (range: 140-205 minutes), and the median hospital stay was 5 days (range: 3-7 days). Postoperative complications included two cases of UTI, both managed conservatively. At a median follow-up of 19 months (range: 12-31 months), no anastomotic stricture, urinary leakage, or ureteral stump syndrome occurred. Postoperative voiding cystourethrogram (VCUG) revealed no VUR in any patient. Pre- and postoperative APD (22.92 ± 9.07 mm vs. 7.33 ± 5.03 mm, p < 0.001) and UD (11.08 ± 3.15 vs. 5.83 ± 2.41 mm, p < 0.001) differed significantly in the upper pole system, as did the lower pole APD (14.00 ± 6.25 vs. 5.25 ± 3.02 mm, p < 0.001) and UD (7.75 ± 2.26 vs. 4.75 ± 1.36 mm, p = 0.003). The RF of the affected moiety improved significantly (36.58 ± 4.66% vs. 42.75% ± 3.10%, p < 0.001). Robot-assisted reconstruction using UU and Lich-Gregoir UR is a safe and effective approach for complex duplex kidneys requiring concurrent upper- and lower-tract reconstruction, demonstrating durable resolution of obstruction and reflux as well as functional preservation.
Friedreich ataxia (FA), a fatal, autosomal recessive disorder caused by pathogenic variants in the frataxin (FXN) gene, is characterized by progressive neurologic and cardiac disease, with cardiac disease being the major cause of death. Preclinical studies have demonstrated that systemic administration of AAVrh.10hFXN, an rh.10 serotype cardiotropic adenoassociated virus (AAV) vector expressing the normal human FXN coding sequence, reverses the cardiomyopathy in FXN-deficient mice. To assess the safety and preliminary efficacy of administration of AAVrh.10hFXN to adults with FA cardiomyopathy. This nonrandomized clinical trial evaluates the pooled data of 2 independent, open-label, dose-escalation trials that used the same gene therapy vector and similar clinical protocols among patients with FA cardiomyopathy at academic medical centers. Data were collected from February 22, 2022, to October 4, 2025, for trial 1 and from February 14, 2023, to September 10, 2025, for trial 2 and analyzed together from November 5, 2025, to March 12, 2026. AAVrh.10hFXN, administered intravenously in 3 dose cohorts (1.8 × 1011, 5.6 × 1011, and 1.2 × 1012 vector genomes per kilogram of body weight). In addition to safety as the primary outcome, multiple parameters of exploratory end points were assessed, including cardiac biopsy levels of FXN protein, cardiac magnetic resonance imaging-derived left ventricular mass index (LVMI), and serum high-sensitivity (hs) troponin I. Seventeen patients with FA cardiomyopathy (mean [SD] age, 25 [6] years; 11 [65%] female) were followed up for a mean (SD) of 20 (8) months. There were 4 serious adverse events, 3 possibly related to prednisone immunosuppression and 1 possibly vector-related myocarditis 12 months after therapy, all of which resolved. Other adverse events were transient, nonserious, or not treatment related. In all 8 patients with cardiac biopsy 3 months after therapy, there were higher levels of cardiac FXN (dose cohort 1, 20%; cohort 2, 81%; cohort 3, 123%). After therapy, LVMI was lower by at least 10% in 9 patients and stabilized in 8 patients. Excluding the patient with myocarditis, posttherapy values of serum hs troponin I were lower by at least 10% in 15 patients and higher by at least 10% in 2 patients. Findings of this nonrandomized clinical trial suggest that intravenous administration of AAVrh.10hFXN was well tolerated and may be a potential treatment for FA cardiomyopathy, as evidenced by preliminary improvement in exploratory efficacy end points. ClinicalTrials.gov Identifiers: NCT05302271 and NCT05445323.
Inhibition of WEE1, a tyrosine kinase responsible for G2 arrest, results in premature mitotic entry and double-strand DNA breaks. Adavosertib is a selective, ATP-competitive, and small-molecule WEE1 kinase inhibitor. In an adavosertib single-agent, Phase I trial, partial responses (PRs) were observed in patients with solid tumors carrying pathogenic variants (PVs) in BRCA1/2. In this trial, we further evaluated adavosertib in patients with PV in BRCA1/2 solid tumors. Eligible patients met criteria for the National Cancer Institute-Molecular Analysis for Therapy Choice master protocol and had a diagnosis of advanced BRCA-mutated solid tumor (germline or somatic mutations were accepted); 33 patients were enrolled, and 30 received study treatment. Adavosertib was administered orally, 300 mg once daily, with 5 days on and 2 days off over a 3 week cycle of 2 weeks on and 1 week off, until disease progression or unacceptable toxicity. Radiologic assessment was performed every three cycles. The primary end point was overall response rate (ORR); secondary end points included 6-month overall survival (OS6) and 6-month progression-free survival rate (PFS6). The ORR was 3.3% (90% CI, 0.2 to 14.9); the OS6 was 57.3% (90% CI, 41.9 to 72.7); the PFS6 was 23.4% (90% CI, 10.7 to 36.2). One PR (fallopian tube serous carcinoma) and six cases of stable disease (SD, >6 months) were observed. In patients with SD <6 months or progressive disease (nonresponders), significantly increased PI3K/AKT/mTOR signaling pathway gene transcripts suggested activation of this resistance mechanism. The primary reason for treatment discontinuation was disease progression. Common side effects included myelosuppression, fatigue, nausea, anemia, vomiting, and diarrhea. In heavily pretreated, advanced solid tumor patients with PV in BRCA1/2, adavosertib treatment resulted in low ORR, and this trial did not meet the primary end point.
Hypopigmented mycosis fungoides (HMF) is uncommon in adults, and data on clinicopathologic features and long-term outcomes remain sparse. To investigate the clinicopathologic features and outcomes of adults with HMF in a large multicenter cohort. This retrospective multicenter cohort study conducted from January 2011 to October 2023 at 6 US tertiary referral centers and included adults (18 years or older at diagnosis) with biopsy-confirmed HMF and hypopigmentation documented at diagnosis, with a median (range) follow-up of 39 (1-347) months. Data were analyzed from February to December 2025. Clinical variant, immunophenotype predominance, and polymerase chain reaction-based T-cell receptor (TCR) gene rearrangement in peripheral blood and/or skin. Best overall response, defined as complete response, partial response, stable disease, or progressive disease, and progression to a higher stage. The cohort included 224 adults with HMF (median [range] age, 44 [18-74] years), of whom 164 (73%) were women (60 men [27%]), 5 (2%) were Asian individuals, 1 (0.4%) was a Hispanic/Latino individual, 1 (0.4%) was a Middle Eastern individual, 19 (8%) were White individuals, and 186 (83%) were Black individuals; 219 (98%) presented with early-stage disease. Most had hypopigmented lesions only (159 [71%]), whereas 65 (29%) exhibited mixed-variant mycosis fungoides; outcomes were similar between groups. Among 141 patients with available immunophenotyping, 88 (63%) had CD8-positive predominance. Among 207 treated patients, most (179 [90%]) received skin-directed therapy alone. Among 198 evaluable patients, the best overall response was complete response for 52 (26%), partial response for 101 (51%), stable disease for 34 (17%), and progressive disease for 11 (6%). Over a median (range) follow-up of 39 (1-347) months, 14 of 224 patients (6%) experienced progression to a higher stage, including 5 of 219 patients (2%) with early-stage disease at baseline who experienced progression to advanced-stage disease. Peripheral blood TCR monoclonality was detected in 23 of 85 tested patients (27%) and was associated with poorer treatment response but not with disease progression. The finding of this cohort study suggest that adult HMF demonstrated a generally indolent course, with favorable response to skin-directed therapy, irrespective of immunophenotype or mixed-variant presentation. Peripheral blood TCR monoclonality was associated with lower treatment response but not disease progression.
Primary splenic angiosarcoma (PSA) is a rare vascular malignancy with a poor prognosis and limited therapeutic options. A 62-year-old man with metastatic PSA underwent splenectomy followed by first-line paclitaxel, achieving stable disease for 7 months. Disease progression manifested as hepatic and bone marrow metastases with tumor-induced hepatic failure and refractory thrombocytopenia. Sequential treatment with liposomal doxorubicin, eribulin, toripalimab, and lenvatinib failed to control the disease failed to control the disease. Genomic profiling identified a PIK3CA p.P471L missense mutation. A combination regimen of inavolisib (a selective PI3Kα inhibitor) and lenvatinib was initiated. Bilirubin levels normalized, and platelet counts recovered within 2 weeks; follow-up MRI confirmed radiological stabilization. At 16 months postdiagnosis, the patient remains alive on this regimen, though long-term durability of response has yet to be determined. To our knowledge, this is the first reported use of inavolisib in angiosarcoma. The rapid biochemical and radiological response observed in this PIK3CA-mutated PSA supports early genomic profiling to identify actionable alterations and warrants prospective evaluation of combined phosphoinositide 3-kinase and vascular endothelial growth factor pathway inhibition in refractory angiosarcoma.
Research on the relationship between age-related macular degeneration (AMD) and secondary fracture risk following hip fractures is scant. We aimed to examine whether AMD increases the risk of secondary fractures following hip fracture surgery. This retrospective cohort study was conducted using data from the Korean National Health Insurance Service Senior Cohort (2002-2019). Secondary fractures were defined as hip, wrist, humerus, spine, ankle, or pelvic fractures occurring within 6 months after hip fracture surgery. Patients diagnosed with AMD within 6 months postoperatively were identified. Covariates included age, sex, income, insurance type, Charlson Comorbidity Index, residential area, disability status, and hospital size and type. Associations between AMD and secondary fractures were analyzed using Cox proportional hazards models. Among 18 611 patients with hip fractures, 93 were diagnosed with AMD and 26 experienced secondary fractures. Patients with AMD had a significantly higher risk of secondary fractures than those without AMD (adjusted hazard ratio, 1.70; 95% confidence interval, 1.16-2.51). Overall, AMD was associated with an increased risk across all fracture types. Effective management of AMD may help reduce the risk of secondary fractures.
Radiotherapy is seldom required in patients with prolactinoma, except in few cases resistant to standard treatment. We report the long-term outcome of Gamma Knife radiosurgery in a consecutive series of patients with prolactinoma resistant to both dopamine agonists and surgery. Observational study. Tertiary reference center for surgery and radiosurgery in patients with pituitary adenoma. We investigated 44 consecutive patients with prolactinoma resistant or intolerant to drugs who underwent radiosurgery at our center between 1994 and 2024. End points of the study were normalization of prolactin either on or off medical therapy, control of tumor growth, and toxicity. After a median follow-up of 92 months, the 5- and 10-year-probability of remission off drug therapy was 35.7% (95% confidence interval, 18.7-52.7%) and 49.0% (95% confidence interval, 29.6-68.4%), respectively, while the 5- and 10-year-probability of remission in the 20 patients on drug therapy was 51.1% (95% confidence interval, 26.7-75.5%) and 58.5% (95% confidence interval, 33.1-83.9%), respectively. Twelve of the 13 women with infertility (92.3%) spontaneously conceived during follow-up. Recurrence of the tumor occurred in 3 patients (6.8%). The 5- and 10-year-recurrence free survival was 93.5% (95% confidence interval, 84.5 - 100%) and 88.6% (95% confidence interval, 75.8 - 100%), respectively. Severe trigeminal neuralgia lasting for six months occurred in one patient. New pituitary deficits occurred in two patients. Gamma Knife radiosurgery provides durable tumor control and hormonal improvement in patients with prolactinoma refractory to medical and surgical therapy. Side effects, including hypopituitarism, are uncommon.
BackgroundDespite substantial global progress in HIV prevention and treatment, mother-to-child transmission (MTCT) of HIV remains a major public health challenge in sub-Saharan Africa, which accounts for approximately 65% of the world's 39.9 million people living with HIV. Vertical transmission rates vary substantially across regions and over time. We conducted a systematic review and meta-analysis to estimate the overall, temporal, regional, and country level prevalence of HIV MTCT in sub-Saharan Africa.MethodsThis research was conducted between June 2024 and May 2025, in accordance with PRISMA guidelines and a protocol registered in PROSPERO (CRD42025637989). We systematically searched six databases (MEDLINE, Embase, PubMed, ScienceDirect, Web of Science, and the Cochrane Library) for articles published in English or French. We included cross-sectional, cohort, and case-control studies involving HIV-positive pregnant women aged ≥18 years that reported MTCT prevalence. Two reviewers independently screened, extracted data, and assessed study quality (Joanna Briggs Institute and Newcastle-Ottawa Scale). Pooled prevalence and 95% CI were calculated using a random-effects model in STATA 17. Heterogeneity (I2), subgroup analyses (by period, region, country), sensitivity analysis, and funnel plots for publication bias were performed.ResultsFrom 5,848 records, 48 studies (86,376 mothers; 2,875,104 infants) across 15 countries were included. The pooled MTCT prevalence was 7.0% (95% CI 5.2-9.4%; I2 = 99.1%). Temporal trends showed a decline from 26.0% (1993-2000) to 8.0% (2001-2010) and 5.0% (2011-2023). Regionally, West Africa had the highest prevalence (12.1%; 95% CI 6.5-21.6%), Southern Africa had the lowest (4.7%; 95% CI 2.6-8.1%). Approximately 9% of HIV-exposed infants were infected by 24-48 months, 6% were infected by 24 months after enrolment, and 7% tested positive at their first HIV test conducted between 1 and 12 weeks of age.ConclusionAlthough MTCT rates have declined, the current 7.0% remains above the WHO target (<5%) with noted significant regional and national disparities. However, this rate should be interpreted cautiously due to the extremely high heterogeneity (I2 = 99.1%) knowing it's a directional synthesis of available evidence rather than a precise population-level figure.
To compare 24-month persistence and compliance of denosumab with alendronate in postmenopausal women with osteoporosis across 5 Asia-Pacific territories. This prospective cohort study included women aged ≥ 50 years from Australia, Taiwan, South Korea, Hong Kong, and Singapore. Participants received either a bi-annual denosumab injection or weekly oral alendronate as osteoporosis treatment, based on physician judgment. Multivariable logistic regression assessed whether therapy (denosumab or alendronate) was significantly associated with treatment persistence and compliance over 24 months of follow-up. The models were adjusted for age, fracture history, baseline bone mineral density (BMD), prior osteoporosis therapy, and prior oral glucocorticoid treatment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Among 687 enrolled patients, 549 completed their 24-month visit (295 in denosumab and 254 in alendronate group). Patients in the denosumab group were older and a higher proportion previously received osteoporosis treatment. Overall treatment persistence and compliance were 74.9% and 56.6%, respectively. Patients prescribed with denosumab exhibited higher persistence (86.1% vs. 61.8%; P < 0.001) and compliance (62.4% vs. 50.0%; P = 0.004), compared with those on alendronate. Regression results also demonstrated that patients receiving denosumab were more likely to be persistent (aOR = 3.91; 95% CI 2.52-6.08), and compliant (aOR = 1.61; 95% CI 1.12-2.31). BMD T-scores improved in both the treatment groups after 24 months with no significant association between treatment type and change in T-score. No significant difference was also observed in the occurrence of adverse events between the two treatment cohorts. Patients on alendronate reported gastrointestinal issues more frequently, whereas those on denosumab had a higher incidence of bone and joint injuries. Postmenopausal women with osteoporosis were more likely to be persistent and compliant with a bi-annual denosumab injection, compared with weekly oral alendronate.
The Coalition (Globus Medical) hybrid PEEK-titanium cage has been widely utilized in our practice for Anterior Cervical Discectomy and Fusion (ACDF) over a 5-year period. A preliminary review of all the cases that we performed in these five years show to us an unexpectedly high rate of postoperative cage subsidence with the Coalition (Globus Medical) stand-alone cage. This prompted a formal investigation, the purpose of this study was, therefore, to systematically determine the true rate of subsidence for the Coalition cage in our cohort and to identify the independent risk factors that could explain this finding. We conducted a retrospective analysis of 70 consecutive patients who underwent ACDF with the Coalition cage between 2018 and 2023. Data on demographic, clinical, and surgical variables were collected. The primary outcome was cage subsidence (≥ 3 mm) assessed on lateral radiographs at a mean follow-up of 28.8 months (range 12-48). Independent predictors were identified through a multivariable logistic regression model constructed using the purposeful selection of covariates strategy, a multi-step iterative process that accounts for both statistical significance and confounding effects. The overall patient-based subsidence rate was 38.6% (27 of 70 patients) at a mean radiographic follow-up of 28.8 months. Interrater reliability for subsidence assessment was substantial (Kappa = 0.759). In the multivariable analysis, preoperative diagnosis of radiculopathy was identified as the only independent predictor of subsidence, with an Adjusted Odds Ratio of 3.51 (95% CI: 1.13-10.91, p = 0.029). Contrary to initial assumptions, multi-level surgery (p = 0.441), smoking status (p = 0.615), and implant dimensions were not significant predictors in this cohort. The Coalition cage demonstrated a high rate of subsidence in this series. A preoperative diagnosis of radiculopathy was the primary independent risk factor for this outcome, rather than multi-level fusion or specific implant characteristics. These findings suggest that the biomechanical requirements of disc height restoration in patients with radiculopathy may predispose them to higher subsidence rates when utilizing this specific standalone integrated fixation device.
Retrospective population-based nationwide cohort study. To determine the incidence, risk factors, and optimal surveillance interval of postoperative VTE after degenerative spine surgery. VTE, including pulmonary embolism (PE), is a leading cause of postoperative morbidity and mortality after spine surgery. Recent evidence suggests that VTE risk may already be elevated before surgery, yet the temporal distribution of postoperative VTE risk and the appropriate duration of surveillance remain poorly defined. A total of 200,792 adults who underwent degenerative spine surgery in Korea between 2014 and 2018 were identified from the Korean Health Insurance Review and Assessment Service database. Overall VTE, PE, and VTE-related invasive procedures were estimated as incidence rates per 10,000 person-years over a mandatory one-year follow-up. Multivariable logistic regression with bootstrap validation was used to identify risk factors. Sequential trends were assessed across twelve 30-day intervals, with subgroup analyses stratified by age, spinal region, and comorbidities. Postoperative VTE occurred in 1,282 patients (0.64%), PE in 321 (0.16%), and invasive procedures in 213 (0.11%), with annual incidence rates of 64, 16, and 11 per 10,000 person-years, respectively. Independent risk factors included older age, congestive heart failure, cerebrovascular and peripheral vascular disease, renal disease, end-stage renal disease, concurrent knee arthritis, and thoracic or lumbar surgery. Sequential analysis showed that 61% of all VTE events occurred within the first four postoperative months, peaking in month 2. Subgroup analyses demonstrated delayed return to baseline and additional late-phase peaks among older adults, patients with thoracic pathology, and those with renal comorbidities. Postoperative VTE risk remains elevated for up to four months following degenerative spine surgery, with high-risk subgroups demonstrating additional late-onset events. These epidemiologic findings underscore the importance of maintaining thromboembolic vigilance beyond the conventional early perioperative window, though prospective studies will be necessary to translate these observations into actionable clinical guidelines. III.
This study investigated how specific narcissistic traits and gelotophobia (fear of being laughed at) predict changes in depressive symptoms and negative affect during the first three months of treatment in individuals with personality disorders. Forty-eight patients (75% female, M age = 31.76) with personality difficulties participated in group psychotherapy. Outcome variables were depressive symptoms (PHQ-9) and negative affect (PANAS-X), measured pre-intervention and after 3 months of psychotherapy. Hierarchical regressions were conducted to test the hypotheses. The analyses corrected for the nested data structure. Narcissistic neuroticism significantly predicted increases in both depressive symptoms (β = -0.501, p = .005) and negative affect (β = -0.571, p = .001). Gelotophobia was correlated with symptom worsening but did not add predictive value beyond narcissistic neuroticism. Narcissistic neuroticism is a key predictor of early symptom deterioration in group psychotherapy. Pre-treatment assessment of this trait may help clinicians anticipate early distress and adjust therapeutic interventions accordingly.