Citations

ABSTARCT BACKGROUND: IRRAflow is a novel active cerebrospinal fluid (CSF) exchange system for the treatment of hemorrhagic strokes and intracranial infections. It is a closed system that irrigates various medications dissolved in irrigation solutions at a speed of up to 180 mL/h, expediting resolution. Disrupting this closed system to withdraw CSF samples or infuse medications is necessary in certain circumstances. We report our novel approach for maintaining the sterility of the closed IRRAflow system using a needleless extension and assess the compatibility and safety of this technology throughout treatment. METHODS: We used a needleless extension to withdraw CSF samples and deliver medications to 5 patients treated with the IRRAflow system. We used 1 stopcock with a 3-way valve, 2 neutral needleless connectors, and 2 antiseptic caps. The stopcock was connected between the irrigation and drainage ports of the catheter. The needleless connectors were mounted at the 12 o’clock position of the attached stopcock and the irrigation port with antiseptic caps covering the distal ends. To initiate fluid exchange, the 2 needleless connectors were separated. The extra stopcock valve was connected between the drainage arm, the cassette, and the irrigation arm. The needleless connectors remained mounted at the 12 o’clock position of the stopcock and irrigation port throughout treatment. RESULTS: The needleless connectors mounted on the 12 o’clock position of the stopcock and irrigation port on the drainage and irrigation arms, respectively, provided efficient management of fluid exchange, CSF fluid sampling, and medication delivery. Our needleless extension was compatible with the IRRAflow device and prevented secondary infections despite repeated CSF sampling and medication delivery. CONCLUSION: The needleless extension facilitated a simple and safe interaction with the closed IRRAflow system without compromising the sterile environment during CSF sampling and medication delivery.

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Background/Objectives: Mild cognitive impairment (MCI) affects multiple functional and cognitive domains, rendering it challenging to diagnose. Brief mental status exams are insensitive while detailed neuropsychological testing is time-consuming and presents accessibility issues. By contrast, the Oculo-Cognitive Addition Test (OCAT) is a rapid, objective tool that measures oculometric features during mental addition tasks under one minute. This study aims to develop artificial intelligence (AI)-derived predictive models using OCAT eye movement and time-based features for the early detection of those at risk for MCI, requiring more thorough assessment. Methods: The OCAT with integrated eye tracking was completed by 250 patients at the Mayo Clinic Arizona Department of Neurology. Raw gaze data analysis yielded time-related and eye movement features. Random Forest and univariate decision trees were the feature selection methods used to identify predictors of Dementia Rating Scale (DRS) outcomes. Logistic regression (LR) and K-nearest neighbors (KNN) supervised models were trained to classify PMCI using three feature sets: time-only, eye-only, and combined. Results: LR models achieved the highest performance using the combined time and eye movement features, with an accuracy of 0.97, recall of 0.91, and an AUPRC of 0.95. The eye-only and time-only LR models also performed well (accuracy = 0.93), though with slightly lower F1-scores (0.87 and 0.86, respectively). Overall, models leveraging both time and eye movement features consistently outperformed those using individual feature sets. Conclusions: Machine learning models trained on OCAT-derived features can reliably predict DRS outcomes (PASS/FAIL), offering a promising approach for early MCI identification. With further refinement, OCAT has the potential to serve as a practical and scalable cognitive screening tool, suitable for use in clinics, at the bedside, or in remote and resource-limited settings.

ABSTRACT Lymphocytic colitis (LC) is a subtype of microscopic colitis, often associated with chronic watery diarrhea and characterized by an increase in intraepithelial lymphocytes. Although various medications are implicated in drug-induced LC, its incidence as a treatment-related adverse effect of rearrangement during transfection-selective tyrosine kinase inhibitors is not known. We report a case of pralsetinib-induced LC in a patient with stage 3c nonsmall cell lung cancer. This case highlights pralsetinib-induced LC as a cause of persistent diarrhea that is refractory to standard antidiarrheal treatments and prompts gastrointestinal evaluation and histopathological examination to facilitate early diagnosis and management.

BACKGROUND: Chronic anal fissures are a painful condition characterized by a tear in the anal mucosa. Botulinum toxin injection is a minimally invasive treatment option, but long-term effectiveness in recurrent or persistent cases remains unclear. OBJECTIVE: This study evaluates the long-term outcomes of botulinum toxin injections for the treatment of chronic anal fissures. DESIGN: This study is a retrospective review. SETTINGS: The study was conducted at a tertiary academic center. PATIENTS: Adults with chronic anal fissures treated with botulinum toxin between 2018 and 2023 were included. MAIN OUTCOME MEASURES: Short- and long-term healing, recurrence, or persistence after botulinum toxin injection. Persistent or recurrent fissure(s) were followed for outcomes after subsequent repeat injections or surgery (lateral internal sphincterotomy or fissurectomy). RESULTS: Among 161 patients, 45.3% (n = 73) experienced short-term healing after botulinum toxin as first-line therapy, but only 26% (n = 42) had sustained healing. Subsequent treatment patterns were similar for recurrent (n = 31) and persistent (n = 88) fissures: 35% versus 31% no further intervention, 55% versus 42% multiple subsequent injections, 10% versus 23% surgery, respectively. Sustained healing was achieved in 63% (n = 10/16) of patients who underwent surgery compared with 37% (n = 14/38) who had repeat botulinum toxin injections ( p = 0.06). Only 49% achieved sustained healing after a single injection, multiple injections, or injection(s) with surgery. Complications included 5 episodes of mild fecal incontinence in the botulinum toxin group and 2 instances of surgical site infection in the surgery group. LIMITATIONS: Limitations include a single-institution, retrospective study design and loss to follow-up. CONCLUSION: Botulinum toxin remains a valuable therapy for chronic anal fissures. Many patients have persistent or recurrent fissures after botulinum toxin injection and undergo additional interventions. Despite multiple interventions, only half of the patients achieved sustained healing, regardless of the treatment pattern. These data do not support the use of botulinum toxin over surgery for the treatment of chronic fissures, are helpful for counseling patients on the safety profile of each, and set expectations regarding the need for multiple interventions. See Video Abstract . RESULTADOS A LARGO PLAZO DEL USO DE TOXINA BOTULÍNICA EN EL TRATAMIENTO DE FISURAS ANALES CRÓNICAS: UN ENFOQUE GRADUAL PARA EL MANEJO DE CASOS RECURRENTES Y PERSISTENTES ANTECEDENTES: Las fisuras anales crónicas son una afección dolorosa caracterizada por un desgarro en la mucosa anal. La inyección de toxina botulínica es una opción de tratamiento mínimamente invasiva, pero su eficacia a largo plazo en casos recurrentes o persistentes sigue sin estar clara. OBJETIVO: Evaluar los resultados a largo plazo de las inyecciones de toxina botulínica para el tratamiento de las fisuras. DISEÑO: Revisión retrospectiva. ENTORNO: Centro académico terciario. PACIENTES: Adultos con fisuras crónicas tratados con toxina botulínica entre 2018 y 2023. PRINCIPALES MEDIDAS DE RESULTADO: Curación a corto y largo plazo, recurrencia o persistencia después de la inyección de toxina botulínica. Se realizó un seguimiento de las fisuras persistentes o recurrentes para evaluar los resultados después de repetidas inyecciones o cirugía (esfinterotomía interna lateral o fisurectomía). RESULTADOS: Entre los 161 pacientes, el 45,3 % (n = 73) experimentó una curación a corto plazo tras la toxina botulínica como terapia de primera línea, pero solo el 26 % (n = 42) tuvo una curación sostenida. Los patrones de tratamiento posteriores fueron similares para las fisuras recurrentes (n = 31) o persistentes (n = 88): 35 % frente a 31 % sin intervención adicional, 55 % frente a 42 % con múltiples inyecciones posteriores, 10 % frente a 23 % con cirugía, respectivamente. Se logró una curación sostenida en el 63 % (n = 10/16) de los pacientes que se sometieron a cirugía, en comparación con el 37 % (n = 14/38) que recibió inyecciones repetidas de toxina botulínica ( p = 0,06). Solo el 49 % logró una curación sostenida después de una sola inyección, múltiples inyecciones o inyecciones con cirugía. Las complicaciones incluyeron 5 episodios de incontinencia fecal leve en el grupo de la toxina botulínica y dos casos de infección en el sitio quirúrgico en el grupo de la cirugía. LIMITACIONES: Estudio retrospectivo de una sola institución y pérdida de seguimiento. CONCLUSIÓN: La toxina botulínica sigue siendo una terapia valiosa para las fisuras anales crónicas. Muchos pacientes presentan fisuras persistentes o recurrentes tras la inyección de toxina botulínica y se someten a intervenciones adicionales. A pesar de las múltiples intervenciones, solo la mitad de los pacientes lograron una curación sostenida, independientemente del patrón de tratamiento. Estos datos no respaldan el uso de la toxina botulínica frente a la cirugía para el tratamiento de las fisuras crónicas, pero son útiles para asesorar a los pacientes sobre el perfil de seguridad de cada una y establecer expectativas con respecto a la necesidad de múltiples intervenciones. ( AI-generated translation )

ABSTRACT Melanocortin‐4 receptor (MC4R) deficiency is the most common cause of monogenic obesity; yet treatment options for children with MC4R mutations are limited. We describe significant improvement in weight in three patients with pathogenic or likely pathogenic MC4R mutations; two adolescents treated with semaglutide, and a younger child treated with metformin and topiramate. These findings indicate GLP‐1 receptor agonists, topiramate and metformin can be helpful in managing obesity associated with MC4R deficiency.

Abstract Rationale Mucus plugs occur in chronic obstructive pulmonary disease (COPD), but little is known about their size and airway location or whether these mucus plug features change as emphysema worsens. Methods Computed tomographic lung scans from 31 participants with COPD from the SubPopulations and InteRmediate Outcomes In COPD Study (SPIROMICS) cohort were analyzed to quantify mucus plug size and airway location and extent of emphysema. Radiologist annotations of mucus plugs were incorporated in an image processing pipeline to generate size and location information. Emphysema was quantified as the percentage of voxels less than -950 Hounsfield units. Measurements and Main Results The length distribution of 563 annotated mucus plugs varied from 2 to 50 mm. The distribution was multimodal, and an 11-mm length defined short (“stubby,” ≤11 mm) and long (“stringy,” >11 mm) plug phenotypes, with stubby plugs being most common (64%). Mucus plugs localized predominantly to airway generations 6 to 9, and their prevalence was highest in lower lobes. On a lobar basis, the mucus plug number decreased as emphysema percentage increased, whereas average mucus plug volume tended to increase. Conclusion COPD is characterized by mucus plugs of varying size and shape, and emphysematous lung regions may be differentially susceptible to formation of these plugs. The location of mucus plugs in segmental and subsegmental airways in COPD makes them amenable to treatment with inhaled medications or bronchoscopy.

Abstract Background Reference sets are needed to evaluate performance of multi-cancer detection (MCD) assays. The National Cancer Institute funded the Alliance reference set study to assess MCDs for use in future trials. Methods Individuals with cancer and controls were recruited; blood specimens were collected prior to cancer treatment. A performance evaluation study was designed utilizing reference set samples. Companies (n = 6) were selected to participate based on review of performance data and ability to utilize the blood collection tube. Companies received samples from cancer types their assay was designed to detect (“targeted”), plus additional “non-targeted” and control samples. Companies reported positive/negative calls, risk scores, and tissue-of-origin (TOO) predictions. Sensitivity was computed for early (I-II) and late (III-IV) stage cases, based on positive/negative calls (SEPN) and at fixed 98% specificity (SE98). Specificity and TOO accuracy were computed. Results Five hundred and forty nine cases (encompassing 13 cancer types) and 413 controls from the reference set were included in the study. Companies assessed samples from median 6 (range 5-9) targeted cancer types and median 8 (range: 7-11) overall cancer types. Median (range) specificity was 92.3% (76.5%-98.5%). Median (range) SEPN was 32% (25%-42%) for early stage and 73% (48%-89%) for late stage; while median (range) SE98 was 19% (8%-35%) for early stage and 66% (13%-79%) for late stage. Median sensitivity for non-targeted types was 40% (early stage) and 52% (late stage). Median (range) TOO accuracy (primary predicted site) was 75% (64%-78%). Conclusions Sensitivity and specificity varied widely across assays with early-stage sensitivity substantially lower than late-stage sensitivity. Clinical Trial Registration Number ClinicalTrials.gov identifier NCT05334069.

Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with Type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischaemic stroke and examined trends and disparities. Methods and results Using nationwide Czech registry data (2015–24), we identified patients with incident nonfatal MI or ischaemic stroke and confirmed T2D. GLP-1RA users—initiating therapy within 12 months post-event—were propensity score matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality. GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126 845 MI survivors, 28 206 had T2D; the matched cohort comprised 2271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR 0.7; 95% CI, 0.52–0.93), all-cause (HR 0.61; 95% CI, 0.47–0.80), and cardiovascular death (HR 0.54; 95% CI, 0.36–0.80). Among 177 115 stroke survivors, 73 750 had T2D; the matched cohort comprised 2235 patients (385 GLP-1RA; median follow-up 27 months). GLP-1RA use was associated with lower risk of MACE (HR 0.71; 95% CI, 0.54–0.94), all-cause (HR 0.59; 95% CI, 0.46–0.76), and cardiovascular death (HR 0.55; 95% CI, 0.37–0.81). Conclusion GLP-1RA therapy after MI or stroke in T2D was associated with substantially lower risks of MACE, cardiovascular, and all-cause death in real-world practice. Utilization remained low, particularly among women and older adults, underscoring the need for broader and more equitable implementation in secondary prevention.