Citations

Objectives: Histiocytic neoplasms, particularly Erdheim-Chester disease (ECD), exhibit perivascular infiltration, and vertebrobasilar circulation involvement remains poorly characterized. We aimed to describe intracranial vertebrobasilar involvement. Methods: We conducted a case series nested within an observational cohort at a tertiary referral center. We identified patients from a predefined cohort of biopsy-proven histiocytic neoplasms. We included patients with ECD, Langerhans cell histiocytosis (LCH), or Rosai-Dorfman-Destombes disease (RDD) who demonstrated intracranial vertebrobasilar periarterial involvement, defined by MRI evidence of histiocytic infiltration encasing the vertebral and/or basilar arteries. Results: Vertebrobasilar coated artery involvement was present in 3 patients with ECD (3/183, 1.6%), including 1 with mixed ECD-LCH, and 1 patient with RDD (1/88, 1.1%); no cases occurred in isolated LCH (0/144). Two patients with multisystemic ECD had incidental imaging findings without neurological symptoms. One patient developed a progressive brainstem syndrome due to an enlarging perivascular lesion, and 1 patient with RDD developed chronic progressive myelopathy from a cervicomedullary lesion encasing both vertebral arteries. Conclusions: Vertebrobasilar coated artery involvement can occur in histiocytic neoplasms, particularly ECD. Recognition of this imaging pattern may aid neurologists in diagnosis and help prevent neurological complications from compression or ischemic stroke.

Purpose Radioligand therapy (RLT) with [ 177 Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate cancer (mCRPC), including prolonged overall survival (OS) and progression-free survival (PFS), as well as improved quality of life. For patients previously treated with [ 177 Lu]Lu-PSMA-617 who subsequently experience disease progression, retreatment with [ 177 Lu] Lu-PSMA-617 has emerged as a potential approach, yet data on the outcomes of RLT retreatment remains limited. This study aimed to assess the efficacy and safety of retreatment RLT in mCRPC. Methods Clinical and imaging data of patients who underwent at least two cycles of [ 177 Lu] Lu-PSMA-617, followed by a second course of treatment with [ 177 Lu] Lu-PSMA-617 between March 2018 and December 2024, were retrospectively reviewed. Endpoints included biochemical response, imaging response, toxicity, PSA-PFS, rPFS, and OS. Radiologic and biochemical responses were evaluated using RECIST 1.1 criteria and PSA levels, respectively. Results A total of 589 patients underwent [ 177 Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20/589) received RLT retreatment. The median age was 71.3 years (range: 63.7–95.2), and the median follow-up was 73.3 months (95% CI, 35.7–77.2 months) after the initial treatment and 21.7 months (95% CI, 16.9–26.0 months) after retreatment. The initial treatment involved a median of 4.5 cycles (range: 2–6). Following the first course of RLT, 15 patients (75%, 15/20) had exhibited a >50% decline in PSA levels, including 9 who achieved a >90% decrease. Additionally, 12 patients (60%, 12/20) had demonstrated a complete or partial imaging response, while 3 (15%, 3/20) patients had stable disease, and 5 (25%, 5/20) patients had progressive radiologic disease. Patients received a median of 4 retreatment cycles (range, 1–6), and the median interval between initial RLT and retreatment RLT was 33.1 months (IQR, 16.2–48.9 months; range, 10.7–58.8 months). A PSA decline of ≥50% was observed in 9 out of 20 patients (45%, 9/20). An imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, whereas 10 patients (50%, 10/20) showed progression. The median PSA-PFS was 9.8 months (95% CI, 4.1–17.9 months), and the median rPFS was 8.2 months (95% CI, 3.3–17.9 months). Eight deaths occurred during follow-up. The estimated Kaplan Meier OS rates were 83.6% at 12 months (95% CI, 57.3%–94.4%) and 53.7% at 24 months (95% CI, 28.3%–73.7%). Grade 2 renal toxicity was observed in one patient (5%, 1/20). Three patients (15%, 3/20) developed Grade 2 anemia. Notably, no grade 3 or grade 4 adverse events were observed during either treatment period. Conclusion In our cohort, retreatment with [¹ 77 Lu]Lu-PSMA-617 RLT was associated with biochemical and imaging responses in some patients, with observed survival outcomes that support further investigation. However, given the retrospective single-arm design and small sample size, large prospective studies are needed to more rigorously evaluate the safety, efficacy, and optimal patient selection for retreatment RLT.

Abstract Sepsis is a multi-system physiological syndrome defined as a dysregulated host response to infection. Despite recent advances clinicians continue to depend on clinically or physiologically defined syndromes as poor classifiers and therefore fail to accurately predict outcome or responses to treatment. Recent studies suggest that advances in screening, diagnosis, prognosis, and treatment of sepsis can be used to tailor immunomodulatory therapies. In the present narrative review, we critically analyze important academic literature published between January 2025 and June 2026 with a focus on epidemiology, screening, diagnosis, prognosis and personalized management. We believe that sepsis care will soon be defined by the convergence of rapid diagnostics, multi-omics profiling, and artificial intelligence, enabling a shift from generalized treatment approaches toward truly personalized, dynamic patient management. While the scientific and technological foundation for this transformation is emerging rapidly, clinical validation using innovative (adaptive) clinical trial design is required. Successful implementation within routine care will require multidisciplinary collaboration, robust infrastructure, clinician and patient engagement, and healthcare systems capable of integrating innovation into practice. The coming years may see a paradigm shift in sepsis management comparable to advances observed in personalized management of malignancies.

ABSTRACT Non‐allergic rhinitis is a frequent yet underdiagnosed cause of chronic nasal symptoms, including nasal congestion, rhinorrhoea, and upper airway hyperreactivity. Its pathophysiology involves neurogenic dysregulation, leading to excessive mucus production and vasodilation. While medical therapy remains first‐line, some patients experience persistent symptoms requiring surgical intervention. This review outlines key surgical options for refractory non‐allergic rhinitis: inferior turbinate (IT) reduction, vidian neurectomy, and posterior nasal nerve (PNN) ablation. IT reduction—performed using cold instruments, radiofrequency, laser, coblation, or microdebrider—remains the cornerstone treatment for nasal obstruction, offering durable symptom relief with low complication rates. Vidian neurectomy effectively reduces rhinorrhoea but carries risks of ocular dryness and transient facial numbness, limiting its indication to severe, refractory cases. PNN interventions, including cryotherapy, cold‐instrument techniques, and radiofrequency, provide a minimally invasive, outpatient alternative that selectively targets nasal parasympathetic and sensory fibers while sparing lacrimal innervation, yielding significant and lasting symptom improvement. Surgical management of non‐allergic rhinitis is effective and safe when tailored to symptom profile, anatomy, and prior medical treatment response. Advances in endoscopic and minimally invasive approaches have reduced complications, establishing these procedures as integral options in comprehensive non‐allergic rhinitis care.

Background: Smokers with multiple sclerosis (MS) experience worse disease, yet underlying mechanisms remain unknown. Smoking disrupts bile acid and tryptophan metabolism in non-MS populations; both pathways involve host–microbiome co-metabolism and have been linked to MS. Objective: Determine whether smoking perturbs these metabolic pathways in MS and whether such alterations statistically mediate smoking’s effect on MS severity. Methods: We analyzed serum bile acid, tryptophan, and tobacco-related metabolites across four independent MS cohorts ( N = 266) using discovery-replication analyses. Mixed-effects regression assessed replicating associations with current smoking and nicotine exposure. Mediation analyses tested if replicating metabolites were potential mediators between smoking and MS severity. Hypothesis-generating metagenomic analyses explored smoking-associated gut–microbial shifts and metabolite correlations. Results: Current smokers and nicotine-exposed MS subjects had reductions in bile acids and tryptophan metabolites, notably indolepropionate, a neuroprotective, anti-inflammatory gut–microbial metabolite. Lower indolepropionate statistically mediated ~20% of smoking’s adverse effect on MS severity. Metagenomic analyses identified potential smoking-enriched MS-linked taxa, and that indolepropionate broadly co-occurs with microbial networks (e.g. Lachnoclostridium appeared inversely associated with indolepropionate in smokers with MS). Conclusion: Tobacco exposure disrupts host–microbiome tryptophan and bile acid metabolism in persons with multiple sclerosis, with indolepropionate depletion partially mediating disease severity, highlighting a potential mechanistic pathway warranting further investigation in MS smokers.

Background/Objectives: Patients with relapsed/refractory multiple myeloma (RRMM) have poor survival outcomes and limited treatment options. The increasing utilization of multiagent therapies for earlier lines of treatment and novel drug classes including BCMA-targeting agents in subsequent lines of therapy has created a need for innovative treatment platforms in patients who have relapsed after or are refractory to these current standard-of-care approaches. Iopofosine I 131 is a 131iodide (131I)–phospholipid conjugate that exploits the selective uptake and retention of phospholipid ethers through lipid rafts to facilitate tumor delivery of 131I. Methods: The objective of this phase 1 dose-escalation study was to assess the safety and tolerability of single and fractionated dose schedules of iopofosine I 131 + low-dose dexamethasone in heavily pretreated patients with RRMM. Results: The most common AEs overall were cytopenias, notably thrombocytopenia (93.5%), lymphopenia (74.2%), anemia (71%), leukopenia (61.3%), and neutropenia (58.1%). All patients experiencing hematologic adverse events recovered from those events with median time of recovery 21 days post-nadir. Nonhematologic adverse events were mostly limited to Grade 1 and 2. Dose-limiting toxicities included four Grade 4 thrombocytopenia events lasting longer than 7 days, one Grade 4 neutropenia, and one Grade 3 insomnia. The DMC determined 31.25 mCi/m2 was the maximum tolerated dose in the single-dose group, and 20 mCi/m2 × 2 doses was the maximum tolerated dose in the fractionated-dose group. For patients monitored through 85 days following the first infusion, 22 of 26 (84.6%) achieved stable disease after treatment, and 4 of 26 (15.4%) achieved a partial response. Conclusions: A favorable safety and tolerability profile and preliminary clinical activity support further development of iopofosine I 131 in RRMM.