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Polycythemia vera is characterized by erythrocytosis and increased risk of thrombosis. Sapablursen is an antisense oligonucleotide that suppresses transmembrane serine protease 6 (TMPRSS6), increases hepcidin production, and reduces iron availability for erythropoiesis. IMPRSSION; an ongoing phase 2a, randomized, open-label study includes patients meeting 2016 WHO criteria for polycythemia vera, requiring ≥3 phlebotomies within 6 months of screening and ≥1 phlebotomy within the last 12 weeks. Cohort A (120 or 80 mg) and Cohort B (40 mg) received sapablursen subcutaneously once every 4 weeks (Q4W). The primary efficacy endpoint was the reduction in phlebotomy frequency from baseline to weeks 17-37 in patients who received ≥1 dose. Forty-nine patients received ≥1 sapablursen dose (median age 61 years; 82% male). The baseline mean±SD weekly phlebotomy rate was 0.15±0.07 in Cohort A; 0.17±0.07 in Cohort B and was reduced by -0.10 (95%CI, -0.13, -0.07; n=32;p<0.0001) in Cohort A; -0.10 (95%CI, -0.14, -0.06; n=17;p=0.0001) in Cohort B. Sapablursen reduced the median (IQR) number of phlebotomies from 5.0 (3.0-6.0,Cohort A; 3.5-6.5,Cohort B) at baseline (26-weeks) to 0 (0-1.0) in the efficacy evaluation window (20-weeks) in Cohort A and 1.5 (0-2.5) in Cohort B. Most adverse events were mild or moderate; anemia and fatigue were most common. The mean change in MPN-SAF-TSS at week 37 was -6.21 points (95%CI: -10.56, -1.85, p=0.0052) in Cohort A; -2.71 points in Cohort B (95% CI: -8.33, 2.91, p=0.34). Sapablursen reduced phlebotomy need, improved symptoms, and was safe and well-tolerated in patients with polycythemia vera. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov: NCT05143957)

Isolated fallopian tube torsion (IFTT) is a rare form of adnexal torsion. A 2024 review described fewer than 150 cases over several decades. The clinical presentation of IFTT is highly variable and nonspecific, which may result in delayed diagnosis. Most patients present with acute unilateral abdominal pain with nausea and/or vomiting, while other patients may present with more gradual symptoms. Risk factors for IFTT include adnexal lesions, hydrosalpinx, previous pelvic surgery, and pelvic inflammatory disease. Ultrasound is particularly useful in identifying the imaging signs of IFTT, which include normal ovarian size and flow, a distended cylindrical structure that tapers to a “beak” adjacent to the ovary, thickened endosalpingeal folds resulting in a “cogwheel” appearance, and, lastly, a twisted vascular pedicle. We present an imaging-focused case in which the diagnosis of IFTT using ultrasound, following equivocal CT, resulted in prompt and confirmatory surgical management. Our goal is to raise awareness of IFTT as a possibility in females with abdominal pain and to discuss ultrasound characteristics that may increase clinical suspicion and diagnostic confidence. Prompt recognition and surgical management may prevent tubal necrosis and loss of fertility.

IMPORTANCE: Phenobarbital use in ICU alcohol withdrawal syndrome (AWS) may reflect severe or refractory withdrawal and treatment escalation, making multicenter data important to understand its use within ICU practice and its relationship with clinical outcomes. OBJECTIVES: To evaluate phenobarbital use in real-world ICU AWS as a marker of severe or refractory withdrawal and treatment escalation. We also examined its association with time-to-discharge and safety outcomes compared with nonphenobarbital regimens. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study using multiple imputation and propensity score matching. Adults with AWS, defined as Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) score greater than or equal to 10, were included if they received a phenobarbital-based or nonphenobarbital-based regimen in ICUs across a large academic health system from June 30, 2017, to July 1, 2024. Postoperative ICU admissions were excluded. MAIN OUTCOMES AND MEASURES: Primary outcomes were time to ICU and hospital discharge alive from treatment initiation. Safety outcomes were hypotension, new intubation, and aspiration within 48 hours. RESULTS: Of 1216 patients, 345 (28.4%) received phenobarbital. Before matching, phenobarbital-treated patients had higher CIWA-Ar, Acute Physiology and Chronic Health Evaluation III, and pre-ICU benzodiazepine exposure, consistent with more severe or refractory withdrawal. In adjusted time-to-discharge models, phenobarbital use was not significantly associated with time to hospital discharge alive (discharge rate ratio [DRR], 0.91; 95% CI, 0.74–1.12; p = 0.370) or ICU discharge alive (DRR, 0.77; 95% CI, 0.59–1.01; p = 0.057). Hypotension and intubation were similar, and aspiration was less frequent with phenobarbital. CONCLUSIONS: In a contemporary ICU cohort, phenobarbital use reflected treatment escalation in patients with more severe or refractory AWS. After adjustment, time to ICU and hospital discharge alive did not differ significantly, hypotension and intubation were similar, and aspiration was less frequent with phenobarbital. Future studies should define optimal timing, dosing, and patient selection.

Background Stereotactic body radiotherapy (SBRT) is increasingly used for patients with oligometastatic prostate cancer, yet the optimal target definition, dose, and toxicity profile for rib metastases remain uncertain. Objectives We assessed local control (LC), toxicity, and the risk of radiation-induced rib fracture (RF) after SBRT for rib metastases. Design Retrospective multicenter cohort study. Methods We analyzed prostate cancer patients with radiologically diagnosed rib metastases treated with SBRT and >=12 months of follow-up. Outcomes were descriptively compared between gross tumor volume (GTV)-only and GTV plus an intraosseous clinical target volume (CTV) margin. Analyses included Kaplan-Meier survival estimates, cumulative incidence functions, and exploratory univariable Cox and logistic regression; no formal equivalence testing or multivariable validation was attempted because event numbers were very low. Results We included 102 patients with a median follow-up of 20 months. The 1- and 2-year LC rates were 97.9% and 96.3%, respectively. At 3 years, local progression was 2.1% in the GTV-only group, absent in patients treated with >=10 mm margins, and numerically highest with 3-5 mm CTV margins (13.5%, p=0.022). Among 13 symptomatic patients, pain control was excellent, with complete or partial response in all patients within 6 months. No grade >=3 toxicities occurred. RFs were rare (n=3, 2.9%), comprising one symptomatic Grade 2 event (0.9%) and two asymptomatic Grade 1 events (2.0%). Baseline symptoms and extraosseous infiltration were associated with RF in exploratory univariable analysis, but confidence intervals were wide. Higher PTV dose exposure, particularly PTV D50% (36.9 vs. 31.1 Gy, p=0.041), was also observed among RF cases. Conclusions SBRT for rib metastases from prostate cancer was associated with high LC, pain relief, and low observed toxicity in this retrospective real-world cohort. GTV-only contouring may be feasible in carefully selected patients staged and planned with PSMA-PET/CT, but the non-randomized design, baseline imbalances, short follow-up, and very low event count preclude drawing conclusions about equivalence or independent validation. RF predictor analyses should be considered exploratory and hypothesis-generating.

Abstract Objective To evaluate the connection between symptom burden and sexual quality of life in women with idiopathic subglottic stenosis (iSGS). iSGS is a rare fibroinflammatory disorder involving progressive airway narrowing and respiratory distress. While the impact on physical functioning is well‐established, the influence of iSGS on sexual health, a key component of quality of life, remains unexplored. Study Design Anonymized cross‐sectional survey using validated questionnaires. Setting Online international iSGS support group (Living with Idiopathic Subglottic Stenosis). Methods The Dyspnea Index (DI), the Female Sexual Quality of Life (SQOL‐F) questionnaire, and the Medical Outcomes Health Survey (SF‐36) were distributed to an iSGS support group. Only complete responses were analyzed. Associations between DI and sexual quality of life were evaluated using correlation and linear regression. Median‐based symptom burden groupings were used for secondary descriptive comparisons. Results 682 completed all items in the assigned questionnaires and met inclusion criteria. DI scores were inversely correlated with SQOL‐F (Rho = −0.305, P < .001). SQOL‐F was consistently lower among those with high symptom burden across nearly all items; only partner communication showed no difference. Each one‐point increase in DI predicted a 0.61‐point decrease in SQOL‐F ( B = −0.609, P < .001). High‐burden patients also reported significantly lower SF‐36 Physical (PCS) and Mental (MCS) Component Scores. Conclusions Greater airway symptom burden in iSGS is associated with significantly diminished sexual and general health‐related quality of life. These findings reinforce a need for patient‐centered care that considers both physical and psychosocial well‐being.

Abstract General anesthesia increasingly facilitates asleep deep brain stimulation (DBS) surgery but suppresses spontaneous electrophysiological signals used to guide lead placement. Here, we investigated whether evoked resonant neural activity (ERNA), a stimulation-evoked biomarker of basal ganglia circuitry, remains informative during asleep DBS. We analyzed intraoperative recordings from a multisite cohort of 45 patients (86 hemispheres) undergoing subthalamic nucleus or globus pallidus internus DBS under awake and anesthetized conditions. Anesthesia markedly attenuated spontaneous beta and high-frequency oscillatory activity. Although ERNA amplitude was reduced at matched stimulation intensities, increasing stimulation current restored high-amplitude, spatially localized responses while preserving anatomical specificity. Across both targets, ERNA spatial distributions remained stable across awake and anesthetized states, co-localized with established motor-network biomarkers, and retrospectively identified electrode levels associated with the greatest postoperative therapeutic window. These retrospective findings position stimulation-evoked circuit interrogation as a complement to imaging for physiology-guided asleep DBS and as a candidate signal for contact prioritization. Prospective studies are warranted to determine whether ERNA-guided decisions improve placement, programming efficiency and clinical outcomes.

Background Cerebellar tonsillar ectopia may arise from altered cerebrospinal fluid (CSF) dynamics and can mimic Chiari I malformation. Differentiating between pressure-induced tonsillar descent and congenital malformations is essential. We present an interesting case that visualizes variable tonsillar displacement levels as an indicator of CSF dynamics. Case A 3-year-old boy presented with headache and sixth nerve palsy and was diagnosed with idiopathic intracranial hypertension. Initial magnetic resonance imaging (MRI) revealed a 5 mm descent of the cerebellar tonsils. During hospitalization, the patient underwent mastoidectomy for an incidental T2 hyperintense lesion. Subsequent MRI scans demonstrated the resolution of tonsillar displacement. At age 5, the patient experienced worsening headache. Brain MRI revealed a 13 mm descent of the cerebellar tonsils below the foramen magnum and pachymeningeal enhancement. Further evaluation revealed transtemporal CSF leakage through the previous mastoidectomy site into the soft neck tissues. Conclusion This case exemplifies cerebellar tonsillar displacement associated with both intracranial hypertension (push) and hypotension (pull), illustrating opposite causal directions of CSF dynamics in the same patient. Understanding the phenomenon as a result of dynamic CSF balance rather than unidirectional force or fixed pathophysiology can enhance monitoring of patients.

ABSTRACT Objective Idiopathic subglottic stenosis (iSGS) is a rare, fibroinflammatory airway disorder with non‐standardized management. This study aimed to quantify the global clinical variation in surgical strategies for iSGS and identify barriers and facilitators to the adoption of both established and novel techniques. Methods An international cross‐sectional online survey was responded to by 193 clinicians (otolaryngologists, thoracic surgeons, and interventional pulmonologists) across 42 countries. Data on demographics, technique execution, treatment algorithms, clinician satisfaction (7‐point Likert scale), and adoption barriers were collected. Both statistical analysis and thematic analysis were performed. Results Otolaryngologists constituted the majority of respondents (84%), predominantly from Europe (52%) and North America (28%). Endoscopic dilation was nearly universal (95%), but execution was heterogeneous (85% used occlusive balloons, 56% used CO 2 laser). Newer techniques showed varied adoption: In‐office serial intralesional steroid injections were used by 57% of clinicians and the Maddern procedure by 17%. Overall satisfaction with current treatment strategies was moderate (mean Likert score: 5.07; SD = 1.15). Significant variation was found in the definition of treatment failure. Fellowship‐trained surgeons managed higher case volumes and were more likely to perform complex open surgery ( p = 0.019). Key barriers to adoption included lack of experience and insufficient supporting evidence. Conclusion Significant global clinical variation exists in the management of iSGS, affecting surgical technique, adjuvant therapy, and the definition of treatment failure. Standardization of clinical outcomes, continued large‐scale comparative effectiveness trials, and newer efforts aimed at implementing emerging evidence are needed to reduce variability, establish evidence‐based guidelines, and improve global patient care for this complex disease. Level of Evidence 5.