Citations

OBJECTIVE Intramedullary spinal cord tumors (IMSCTs) are typically treated with maximal safe resection, during which neurosurgeons often monitor for neurological injury using muscle motor evoked potential (mMEP) and direct wave (D-wave) neuromonitoring. The predictive value of changes in D-waves for identifying motor outcomes is underexplored. This study evaluated the utility of D-waves for predicting postoperative motor deficits. METHODS Patients who underwent resection of a primary IMSCT with mMEP neuromonitoring from 2003 to 2023 at a tertiary care hospital were identified. Patients who underwent D-wave monitoring in addition to mMEP monitoring were compared to those who underwent mMEP monitoring alone using the Mann-Whitney U-test, chi-square test, and Fisher’s exact test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of D-wave and mMEP monitoring for identifying new neurological deficits immediately postoperatively and at 1 month, 6 months, and last follow-up were calculated. RESULTS After matching, 125 patients were included (median age 42.0 years; 57.6% male; median follow-up 34.0 months), of whom 88 had both mMEP and D-wave data. The most common pathologies were ependymoma (64.0%) and astrocytoma (17.6%). Patients who did and did not undergo D-wave neuromonitoring had similar preoperative neurological function, primary pathology, tumor grade, and tumor location. D-wave use was associated with increased gross-total resection (88.6% vs 64.9%, p = 0.002) and reduced mortality (5.7% vs 24.3%, p = 0.007), length of stay (5.0 vs 6.0 days, p = 0.033), and 30-day readmission (2.3% vs 13.5%, p = 0.013) and reoperation (1.1% vs 10.8%, p = 0.012). At the 6-month follow-up, D-wave monitoring alone was superior to mMEP and combination monitoring for detecting new motor deficits. D-wave monitoring had peak sensitivity (77.8%) and NPV (96.5%) at 6 months and peak specificity (95.8%) and PPV (76.9%) in the immediate postoperative period. CONCLUSIONS D-wave monitoring was associated with reduced mortality and was more accurate than mMEP monitoring alone or combination monitoring for detecting new postoperative neurological deficits. Further prospective studies are needed to validate these results.

Background: Given the faster onset and shorter duration of action of ultra-rapid insulin lispro-aabc (URLi, Lyumjev™ insulin), compared with insulin lispro (a rapid-acting insulin [RAI]), the present study investigated the safety and glycemic outcomes of MiniMed™ 780G advanced hybrid closed-loop (AHCL) use with URLi in youths and adults with T1D. Methods: This 19-site, single-arm, clinical trial enrolled children and adolescents (aged 7–17 years) and adults (aged 18–80 years) with T1D who underwent a run-in period (∼2 weeks) using open loop or automated basal only with an RAI (aspart or lispro), followed by a 3-month study period using URLi with AHCL (AHCL + URLi). End-of-study glycemic metrics and A1c were compared to predefined thresholds and to data from baseline/run-in. Use of recommended optimal settings (ROS, 100 mg/dL glucose target with an active insulin time [AIT] of 2 h) was also assessed. Results: In an intention-to-treat population ( N = 101 pediatric and N = 110 adult participants), percentage of time in range (%TIR) during the last ∼6 weeks of the study period was significantly greater than the predefined thresholds for both the pediatric and adult participants. A1c was unchanged in the pediatric cohort but significantly reduced in the adult cohort (from 7.4 ± 0.9% to 6.9 ± 0.6% [ P < 0.001]). Compared with run-in, study period %TIR and percentage of time in tight target range (%TITR) were significantly increased (pediatric mean %TIRΔ [17.4%] and %TITRΔ [16.0%], respectively, and adult mean %TIRΔ [10.6%] and %TITRΔ [11.6%], respectively; P < 0.001 for all). Additionally, % time above range for both groups was significantly reduced. Use of ROS allowed more participants to achieve recommended glycemic targets. There were no severe hypoglycemia or diabetic ketoacidosis events. Most caregivers agreed that mealtime versus premeal URLi delivery simplified pediatric meal management. Conclusions: Similar to previous studies investigating automated URLi delivery, URLi use in the MiniMed™ 780G system was safe, and glycemic outcomes were favorable for pediatric and adult participants.

Treatment guidelines for Clostridioides difficile infection (CDI) have been published by infectious disease and gastroenterology professional societies; however, adherence in clinical practice remains poorly characterized, particularly for recurrent disease. We conducted a retrospective chart review of 100 patients with CDI (350 episodes: 115 initial, 235 recurrent) referred to a tertiary complicated CDI clinic between 2018 and 2023. Guideline adherence was assessed by comparing treatment with IDSA/SHEA and ACG recommendations, and referring diagnoses were compared with final specialist diagnoses. Guideline adherence was significantly higher in initial compared to recurrent episodes (70.4% vs. 41.3%, p < 0.0001). Among guideline non-adherent recurrent episodes, 51.3% used standard antibiotic regimens inappropriate for the recurrence tier. Specialist review reclassified 12.0% of episodes, with colonization increasing from 2.6% to 8.9%. Misdiagnosed colonization cases had a 6.2-fold higher treatment failure rate than confirmed CDI (39.3% vs. 6.3%, p < 0.0001). Guideline non-adherence showed a non-significant trend toward treatment failure (10.0% vs. 6.7%, p = 0.31). Guideline adherence for recurrent CDI is inadequate in pre-referral settings, and diagnostic misclassification is common. Early specialist involvement may improve both diagnostic accuracy and treatment appropriateness for patients with recurrent CDI.

Management of unstable upper lumbar fractures with corpectomy and posterior fixation is technically demanding, and conventional workflows may require intraoperative repositioning, increasing operative complexity. Lateral mini-open upper lumbar corpectomy (LMULC) paired with robotic-assisted (RA) posterior percutaneous pedicle screw fixation (PPPSF) can be performed in a single position to facilitate ventral spinal decompression and stabilization in the anatomically constrained upper lumbar spine. In this study, we describe the operative technique and report four illustrative cases of unstable L1 or L2 fractures treated with single-position LMULC, RA-PPPSF, and short-segment fusion. Clinical, radiological, intraoperative variables and postoperative outcomes were evaluated. The mean age was 52.3 ± 17.7 years. The median operation time was 314 min (range 268–361 min); the median estimated blood loss (EBL) was 225 mL (range 100–400 mL). The median preoperative kyphosis was 10.15° (range 8.4–14.6°), the median postoperative kyphosis measured 6.65° (range 1.7–10.8°) and the median correction achieved was 3.5° (range −2.4–12.9°). The median visual analog scale (VAS) pain score reduced from 7 (range 7–9) preoperatively to 4.5 (range 2–6) postoperatively at discharge. At a median follow-up of 12 months (range 6–15 months), all patients had uncomplicated recoveries, demonstrated solid fusion on imaging, and reported favorable MacNab outcomes. Single-position LMULC with RA-PPPSF was technically feasible in this preliminary illustrative series and resulted in favorable clinical and radiographic outcomes. However, further studies in larger cohorts are warranted to help confirm these findings and better define the potential advantages and limitations of this technique.

Background: Pancreatitis significantly alters the microbial composition of the oral and intestinal compartments, causing dysbiosis that may contribute to disease mechanisms and potentially serve as a basis for diagnosis or treatment. Objective: To determine whether the oral or gut microbial signature can classify chronic pancreatitis (CP). Methods: Stool samples (n=707) were collected from participants in the Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED). Samples were distributed among 200 healthy (HC), 310 CP, 49 acute pancreatitis (AP), and 148 recurrent acute pancreatitis (RAP). In addition, saliva samples were collected for a subset of participants (n=156). Whole genome sequencing was performed to assess microbiome composition. Machine learning algorithms were utilized to identify a signature with microbial features predictive of CP. Results: Gut alpha diversity was significantly decreased in AP, RAP, and CP compared with HC, with CP exhibiting the lowest diversity. In contrast, oral microbial diversity showed no significant variation across groups. Beta diversity analysis revealed distinct gut microbiome compositions between HC and pancreatitis subtypes, with CP showing the most pronounced differences. Random forest models using gut microbial species demonstrated robust predictive performance for CP using a minimum of 10 species (Area under the curve—AUC: 0.834; accuracy: 0.774). Despite similarities in gut microbiome composition across pancreatitis subtypes, a unique gut microbial signature for CP was identified highlighting the microbiome’s potential in CP diagnosis. Conclusion: Our study reveals a gut microbial signature predictive of CP using machine learning models in a large US multi-institutional cohort.

Abstract The rapid progress in tumour genome sequencing has created a need for bioinformatics tools to interpret the clinical significance of detected variants. VarStack² integrates information from several publicly available resources, including the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, cBioPortal, UCSC Genome Browser, and ClinicalTrials.gov, CIViC and presents it through a user-friendly interface. VarStack2 simplifies the process of retrieving data, saving users significant time compared to manually navigating each database individually. Users can input a variant by specifying a gene symbol, amino acid change, and coding sequence change, with the option to search tumour-specific studies in cBioPortal alongside their primary query. Results are organized into separate sections and can be exported in CSV format for further analysis. Additionally, VarStack2 offers a smart search feature that suggests variants for the gene of interest based on its database search results. These features make VarStack2 a useful tool for scientists and clinicians by enhancing the variant interpretation process and integrating somatic variant information into workflows. VarStack² is freely available at http://varstack.brown.edu/

Abstract Vertebral metastatic disease results from many types of cancer and can have a devastating impact on patient mobility, psychological health, quality of life, and ultimately overall patient survival. However, the development of radiotherapy and surgical techniques has rapidly surged in conjunction with ongoing advances in basic science and translational studies. In this review, we discuss the paradigm shift in our understanding of the epidemiology and treatment algorithms for spinal oncology, ranging from preoperative optimization strategies, radiation and surgical techniques, the utilization of molecular markers and targeted therapeutics in medical oncology, and prognostication tools that underscore a new multidisciplinary approach to spinal oncology care.

Background An increasing number of patients with congenital heart disease (CHD) are pursuing pregnancy with the potential for cardiovascular complications. This study aimed to establish patient‐centered national research and care priorities to improve pregnancy‐related outcomes for individuals with CHD. Methods This mixed‐methods study used a modified Stakeholder Engagement in Question Development methodology to systematically identify patient‐centered priorities. Key activities included consortium engagement (phase 1), patient and provider questionnaires (phase 2), and an in‐person facilitated meeting to explore survey results and follow‐up virtual focus groups (phase 3). Reflexive thematic analysis was used to synthesize short‐ and long‐term research priorities (phase 4). Results Three overarching goals emerged: (1) improving access to specialized CHD, cardio‐obstetrics, and mental health care; (2) improving quality and consistency in clinical care; and (3) increasing patient and community engagement. These goals were then expanded into 5 central themes: (1) communication within the health care setting; (2) community engagement; (3) ancillary clinical support; (4) integration of patient‐reported outcomes; and (5) implementation, education, and knowledge mobilization. Short‐term (1–5‐year) goals included expanded telemedicine use, best practice recommendations for multidisciplinary care coordination, and targeted educational resources. Long‐term (5–10‐year) goals included expansion of adult CHD and cardio‐obstetrics programs, integration of mental health services, and advocacy to improve insurance coverage. Conclusions The consortium provided a national, community‐driven prioritization that highlights actionable pathways to improve pregnancy outcomes for people with CHD. Sustained engagement with patients and community partners is essential to achieving durable improvements across cardio‐obstetric care, education, research, and mental health.

BACKGROUND: Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. METHODS: We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. RESULTS: Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21–1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97–1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10–0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83–1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04–0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15–0.73]). CONCLUSIONS: After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06398366.