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Abstract Background The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM). Methods We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID‐19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age‐adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program. Results Among 3 309 079 individuals aged 15–44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31–1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non‐Hispanic Black individuals and non‐Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups. Conclusion Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non‐Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at‐risk populations. Lay summary Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

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: 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 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 Over 50% of older adults in the US take ≥5 medications, with prevalence reaching 76.8% in the emergency department (ED) setting. However, little is known about their medication self-efficacy (the ability to understand and follow medication regimens), which may influence adherence and adverse drug events when new prescriptions are added during ED visits. Our objective was to determine whether polypharmacy and potentially inappropriate medication (PIM) are associated with self-efficacy. We performed a logistic regression analysis using 5-site multicenter ED survey data linked to electronic health records from patients aged ≥65 years with baseline ED visits during 2019-2021. The predictors were polypharmacy (≥5 medications) and PIM use (≥1 high-risk medication, GEMRx criteria) of prescriptions taken within 1 year of the ED visit. The outcome was low medication self-efficacy (< 11 points MUSE-taking score) assessed at the ED visit. Covariates included insurance, education, marital status, race/ethnicity, caregiver support, dementia status, and frailty. Among 921 patients, 249 (27.0%) had polypharmacy and 66 (7.2%) had PIM use. Low medication self-efficacy was reported by 76 (37.8%) with polypharmacy and 26 (12.9%) with PIM use versus 125 (62.2%) and 40 (5.6%) without. Both polypharmacy (aOR 6.12, 95% CI 2.05-18.22, p = 0.001) and PIM use (aOR 33.65, 95% CI 5.81-214.35, p < 0.001) were associated with greater adjusted odds of low medication self-efficacy. Frailty modified this association, with weaker effects in more frail patients (OR 5.51, 95% CI 2.57-11.8, p = 0.003). These findings suggest that the ED is an important setting to identify older adults who may struggle with medication use.

Purpose: These consensus guidelines by the American Clinical Neurophysiology Society (ACNS) describe best practices for performing intraoperative Electrocorticography (ioECoG) using subdural or depth electrodes for adult and pediatric population. Methods: A group of ACNS members was convened to develop technical standards for performing ioECoG. PubMed searches were performed to identify pertinent peer-reviewed literature. Sections were assigned to individual authors based on expertise. Consensus was achieved during subsequent group discussions to develop evidence-based recommendations to the extent possible. Recommendations: Communication between the neurosurgical and the neurophysiology teams is essential in verifying and documenting the location of the contacts. Most authors recommend ioECoG recordings of at least 5 and up to 30 minutes in duration to allow for sufficient observation of interictal activity. The anesthesia should be adjusted to allow continuous EEG activity and to minimize the effect on the ioECoG recording during general anesthesia or awake surgery. The surgical procedure and technical report should separate ioECoG recordings to define the irritative zone from ioECoG findings during functional mapping. The neurophysiology physician’s physical presence in the operating room is required in the definition of the services. Conclusion: These consensus guidelines by the ACNS describe best practices for performing intraoperative ECoG based on published literature and expert consensus.

BACKGROUND AND OBJECTIVES: Anterior lumbar interbody fusion (ALIF) is a powerful procedure for sagittal correction and indirect decompression in the lumbar spine, though aggressive correction can cause stretch neuropraxia and implant subsidence. The aim of this study was to identify radiographic and clinical predictors of segmental correction, as well as to evaluate the degree to which segmental correction on supine intraoperative radiographs translates to postoperative upright alignment changes. METHODS: We identified patients treated with 1- or 2-level ALIF at a tertiary care center and extracted data on demographics, spinopelvic parameters, and surgical details. Patients treated with isolated ALIF and ALIF with supplementary posterior instrumentation were compared on pre- and postoperative intradiscal lordosis (IDL) and change in IDL. Multivariable linear regression was performed to identify independent predictors of postoperative IDL. RESULTS: We included 204 patients (median age 57 years, 55.4% male) treated at 258 levels, of whom 114 (55.9%) underwent supplementary posterior fixation and 150 (73.5%) underwent single-level implantation. Across all patients, postoperative IDL was significantly greater than preoperative segmental lordosis (25.4° vs 15.3°; P < .001). Standalone ALIF achieved less ΔIDL than circumferential fusion for L5/S1 procedures (7.4° vs 11.6°; P < .001), though ΔIDL for L3/4 and L4/5 was similar between the standalone and circumferential groups. Multivariable analysis showed postoperative IDL to be predicted by greater preoperative IDL (β = 0.26° per degree; [0.15, 0.36]; P < .001), L5/S1 [vs L4/5] implantation (β = 3.97°; [2.72, 5.21]; P < .001), use of supplementary posterior fixation (β = 1.80°; [0.70, 2.89]; P < .001), and greater implant lordosis (β = 0.62° per degree; [0.44, 0.79]; P < .001). CONCLUSION: Postoperative IDL after 1- or 2-level ALIF is best predicted by placement of larger interbody sizes, L5/S1 implantation, greater baseline IDL, and use of adjunct posterior fixation. Patients with higher preoperative lordosis experienced smaller postoperative increases in IDL, though this was likely influenced by a treatment bias.