Publications by Year: 2026

We queried pediatric infectious diseases physicians via the Emerging Infections Network regarding management preferences for Clostridioides difficile infection (CDI). We explored use of vancomycin, fidaxomicin, bezlotoxumab, and fecal microbiota transplantation and found that physicians are increasingly considering newer and adjunctive therapies for pediatric CDI, highlighting the need for updated guidelines.

BACKGROUND: Combined transrectal mpMRI-TRUS targeted (TB) and systematic biopsy (SB) is widely used to diagnose prostate cancer (PCa). However, SB may be omitted in a subset of patients with minimal risk of missing clinically significant prostate cancer (csPCa) in TB alone. We aimed to identify clinical characteristics predicting the need for SB in men undergoing TB.

METHODS: In this retrospective cohort study, 879 patients underwent combined TB and SB. Cases where csPCa was missed by TB but detected by SB were identified. Logistic regression analysis was used to identify clinical predictors for SB necessity, including digital rectal examination, prior negative biopsy, age, prostate-specific antigen (PSA), prostate volume, PSA density, mpMRI tumor volume (MTV), number of mpMRI lesions, PI-RADS score, and mpMRI tesla.

RESULTS: In 80 (9.1%) cases csPCa was missed by TB and detected by SB only. Median MTV was 0.75 cm3 (IQR 0.43-1.41 cm3). Multivariable logistic regression analysis revealed MTV as the only significant predictor of csPCa missed by TB alone (OR=0.52, 95% CI 0.36, 0.75, P<0.001). A larger MTV was inversely associated with the risk of missing csPCa in TB alone. In patients with an MTV greater than 1.36 cm3, the rate of missing csPCa with TB alone was ≤5%.

CONCLUSIONS: MTV is a promising predictor to identify patients who may not require a concomitant SB when undergoing TB. However, this finding needs to be validated in external cohorts before being applied in clinical practice.

OBJECTIVE: Focal brain lesions may underlie generalized tonic seizures, as seen in Lennox-Gastaut syndrome, by engaging bilateral neural networks. However, this seizure type is often not considered surgically remediable. Here, we describe the resolution of apparent electroclinically classic generalized tonic seizures in children originating from a unifocal brain lesion following resective or ablative surgery. This study aims to contribute to emerging evidence that prompt removal of a lesion may resolve generalized seizures by ameliorating aberrant network activity.

METHODS: Boston Children's Hospital's (BCH) epilepsy surgical database was reviewed to identify children with tonic seizures due to a focal brain lesion who remained seizure-free for longer than 1 year following resective or ablative surgery.

RESULTS: Five children were identified, of whom three underwent resective surgery and two laser interstitial thermal therapy (LITT). Age at epilepsy onset varied from 1 month to 7.25 years, and age at first epilepsy surgery ranged from 5.6 to 9.5 years. Lesions were predominantly located in the frontal lobe (n = 3), and focal cortical dysplasia (FCD) was the most common underlying etiology (n = 3), followed by vascular lesions (n = 2). At last follow-up, seizure freedom (Engel Class 1A) ranged between 1.7 and 4.4 years.

SIGNIFICANCE: This study presents evidence that resection or ablation of a focal cortical lesion can resolve generalized tonic seizures. The findings also lend credence to the hypothesis that heterogeneous brain lesions can underlie shared electroclinical features through engaging similar brain networks. Children with tonic seizures in whom a lesional etiology is presumed should undergo timely surgical evaluation, as removal of a focal lesion may arrest the evolution of a secondary epileptic network and allow for the restoration of normal brain network development.

PURPOSE: This study aimed to characterize the clinicopathological, immunophenotypic, and molecular features of gastrointestinal stromal tumors (GISTs) harboring NTRK fusions and to evaluate their diagnostic, prognostic, and therapeutic implications.

METHODS: Twenty-six cases of KIT/PDGFRA/SDH/BRAF wild-type GISTs were evaluated using pan-TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) for NTRK1/2/3, and next-generation sequencing (NGS). Transcriptome analysis was performed on all NTRK fusion-positive cases. Seven KIT-mutant GISTs served as controls. Clinicopathological parameters, IHC profiles, genetic alterations, and treatment responses were analyzed, supplemented by a literature review.

RESULTS: Five of the 26 wild-type GISTs harbored NTRK fusions, all confirmed by NGS as ETV6::NTRK3. Pan-TRK IHC showed 100% sensitivity and 66.7% specificity. All five patients were male; four tumors were intestinal and one gastric. Four cases were high-risk and one very low-risk. Two cases recurred post-resection, showing additional mutations and copy number variations (CNVs). Preliminary evidence from transcriptome sequencing pointed to the possibility that NTRK fusion-positive GISTs represented a heterogeneous group and showed similarities in their molecular profiles to common KIT-mutant GISTs. Both recurrent patients received multi-line TKI therapy (imatinib, sunitinib, regorafenib, ripretinib) with disease progression; one subsequently achieved remission with larotrectinib.

CONCLUSION: NTRK fusion-positive GISTs are rare and exhibit distinct clinicopathological characteristics. FISH and NGS are reliable detection methods, while pan-TRK IHC has limited specificity. Co-occurring genetic alterations may confer aggressive behavior. These tumors respond to TRK inhibition but are resistant to conventional TKIs, underscoring the need for molecularly guided therapy.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13402-025-01146-6.

PURPOSE OF REVIEW: Chronic pelvic pain (CPP), affecting approximately 26% of women globally, is a multifactorial condition with causes including, but not limited to, gynecologic disorders, musculoskeletal disorders, and neuropathic disorders including pudendal neuralgia. A comprehensive evaluation and a multimodal treatment strategy - encompassing medical, minimally invasive non surgical, and surgical therapies - are essential for effective management. This narrative review explores current minimally invasive interventional management options for pudendal neuralgia causing CPP.

RECENT FINDINGS: Pudendal nerve blocks demonstrated pain relief, but the duration of relief varied. Pulsed radiofrequency ablation revealed longer-lasting pain relief compared to pudendal nerve blocks, with several clinical trials and case reports supporting its efficacy. Additionally, neuromodulation techniques, including neuraxial and peripheral nerve neuromodulation, showed promising results in alleviating pain for patients who did not respond to conservative measures. While studies describe interventional therapy for pudendal neuralgia, there is a dearth of randomized controlled trials, which limits the ability to generalize treatment options for pudendial neuralgia. Despite this, current data suggest the possible benefit of interventional management of for pudendal neuralgia.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays are the gold standard for the early diagnosis and risk stratification of acute myocardial infarction (AMI). PERFORM-TSIX (clinicaltrials.gov identifier: NCT06734117) is a prospective, international, observational, longitudinal cohort study to evaluate the clinical performance of the next-generation Elecsys® Troponin T hs Gen 6 assay; the study design is presented here.

OBJECTIVES: The primary objective is to determine the sensitivity of the Troponin T hs Gen 6 assay for the detection of centrally adjudicated AMI diagnosis at 3 h post-emergency department (ED) presentation. Secondary objectives include evaluation of clinical performance at 0, 1-, 5-, and 6-h post-ED presentation and validation of thresholds for a 0/1-h algorithm to rule out AMI. Exploratory objectives include validation of thresholds for a 0/1-h algorithm to rule in AMI and a 0/2-h algorithm to rule in/out AMI and evaluation of prognostic performance at 30 and 180 days.

METHODS: PERFORM-TSIX enrolled 5631 participants across 50 sites from the USA, Europe, China, and Japan. Patients aged ≥ 20 years presenting to the ED with symptoms/signs of acute coronary syndrome were enrolled. All patients were required to have cTn measured as part of their routine care; AMI diagnosis was adjudicated by an independent clinical events committee in accordance with the Fourth Universal Definition of MI, blinded to the results of the Troponin T hs Gen 6 assay.

CONCLUSION: PERFORM-TSIX will determine the clinical performance of the Troponin T hs Gen 6 assay for the diagnosis of AMI in a large, diverse global population.

INTRODUCTION/AIMS: Durable medical equipment (DME)-wheelchairs, non-invasive ventilation, gastrostomy tubes, and communication devices-provides vital support for individuals with amyotrophic lateral sclerosis (ALS). Here, we describe DME use in COURAGE-ALS evaluating reldesemtiv's efficacy and safety in ALS, to evaluate if DME use can be considered an endpoint of interest in ALS trials.

METHODS: COURAGE-ALS, a multicentre, double-blind, randomized, placebo-controlled clinical trial was conducted at 83 sites in the United States, Canada, Europe, and Australia. Participants were randomized 2:1 to receive reldesemtiv or placebo for 24 weeks, followed by 24 weeks of active drug treatment. Exploratory outcomes included reasons for prescribing, extent of use, DME types, and regional differences.

RESULTS: Among 482 participants, 166 (34.4%) were using at least one DME item at baseline. Among 276 participants completing study visits through Week 24, 130 (47.1%) initiated use of a total of 188 new DME items post-baseline through 24 weeks. Manual wheelchairs were most used at baseline (89 items) and initiated (47 items) during the trial. Both baseline DME use and initiating a new item were associated with lower ALS Functional Rating Scale-Revised scores and worse quality of life. The trial was terminated early due to futility. Treatment assignment did not impact DME use. Regional disparities were noted.

DISCUSSION: This study shows that DME is commonly prescribed to ALS trial participants. Further understanding of geographic differences in DME access and their impact on clinical outcomes is warranted prior to including DME use as an endpoint in ALS trials.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: (NCT04944784).

With improvement in medical and surgical care, the number of adults with congenital heart disease (CHD) is soaring. Adults with CHD commonly have impairments in brain health. However, significant gaps in knowledge remain regarding the relevant types and prevalence of neurologic and psychiatric risk and their associated risk factors. We sought to review current evidence, identify gaps in knowledge, and develop key next steps to improve scientific understanding and clinical care. Three working groups-Genetics and Brain Health, Characterizing Neuropsychological and Psychological Outcomes, and Neuropsychological and Psychosocial Interventions-were composed of multidisciplinary experts in relevant clinical and research domains, as well as adults with CHD. Each group identified 5 key knowledge gaps and associated next investigations needed to address those gaps. For Genetics and Brain Health, 5 key knowledge gaps were identified: lack of a standardized neuroimaging protocol for adults with CHD, need to understand neuroradiological-pathological-neuropsychological correlates, role of gene-environment interactions, what can be learned from brain health risk models from other groups, and how existing multimodal approaches influence risk and neuroresilience. Adults with CHD can benefit from routine assessment of brain health, as well as increased clinical and basic research into the underlying factors that contribute to risk and neuroresilience for neurologic and psychiatric sequalae. Multidisciplinary collaborative efforts that incorporate adults with CHD across the research cycle are essential for all key next steps.