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Background Converging evidence hints at neurodevelopmental effects in people at risk of genetic frontotemporal dementia (FTD). Objective We investigated total intracranial volume (TIV), a neuroimaging marker of neurodevelopment, and years of education differences between adult mutation carriers and familial non-mutation carriers, as measures of the structural and functional neurodevelopmental effects of FTD-causing genetic mutations. Methods This cross-sectional cohort study, facilitated through the FTD Prevention Initiative (FPI), included 902 adult pathogenic mutation carriers of GRN , MAPT , or C9orf72 , and 532 familial non-carriers. ANCOVAs were computed to compare TIV and education between groups per gene. Pearson's correlations were used to examine associations between TIV and education. Results Mutation carriers (mean ± SD age = 50.0 ± 13.2 years, sex = 55% female, n ( GRN ) = 298, n( MAPT ) = 187, n ( C9orf72 ) = 417) were compared to familial non-carriers (age = 48.0 ± 12.9 years, sex = 58% female, n ( GRN ) = 201, n( MAPT ) = 114), n ( C9orf72 ) = 217). Consistent with prior findings in young adults, GRN carriers showed larger TIV, on average by 20531 mm 3 , compared to familial non-carriers (95% CI [85.4, 40977], p = 0.049, η 2 p = 0.008). Larger TIV correlated with higher years of education in GRN carriers (95% CI [0.01, 0.24], r (295) = 0.12, p = 0.03) and GRN non-carriers (95% CI [0.08, 0.34], r(198) = 0.21, p = 0.002). MAPT carriers demonstrated smaller TIV than non-carriers, on average by 29896 mm 3 (95% CI [–58248, −1545], p = 0.039, η 2 p = 0.02). Models with C9orf72 and education as outcome variables did not reveal significant differences. Conclusions In support of the neurodevelopmental hypothesis of FTD, GRN and MAPT mutations are linked to structural neurodevelopmental changes in TIV. Further research is needed to identify mechanisms underlying neurodevelopmental influences of FTD mutations and ascertain their suitability as intervention targets.

Bulk messaging is an important population health tool used to engage patients in preventive care and chronic disease management, yet little is known about optimal formatting of the communication. One factor to consider is whether the signatory of the patient-facing communication is the patient’s own Primary Care Provider (PCP) or a generic care team signature. In this quasi-randomized, non-blinded study we compared identical generic bulk outreach messages directed toward patients with an upcoming appointment and invited them to self-schedule a Medicare Annual wellness visit prior to their scheduled PCP appointment. Twenty-eight PCPs (1582 patients) were assigned to the PCP signature group, and 22 PCPs (1289 patients) to the care team signature group. The primary outcome was patient engagement, defined as a reply to the outreach message. Demographic, utilization, and rates of reading the bulk outreach message were similar between groups. Reply rates were significantly higher in the PCP signature group compared with the care team signature group (39.2% vs. 25.2%; odds ratio 1.86; P < 0.001). These findings suggest that using a patient’s own PCP signature in bulk outreach can meaningfully increase engagement, likely leveraging the trust inherent in established PCP–patient relationships. These results may inform health system leaders and population health teams seeking to optimize digital outreach strategies.

Abstract Objective Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by drug‐resistant seizures and developmental slowing. Although cognitive and executive function deficits have been described, their early trajectory is not well understood. Methods The prospective ENVISION natural history study (NCT04537832) assessed cognitive, executive, and adaptive function in children younger than 5 years of age with SCN1A + DS every 6 months for up to 2 years using Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID‐III), Wechsler Preschool & Primary Scale of Intelligence, 4th Edition (WPPSI‐IV), Vineland Adaptive Behavior Scales, 3rd Edition (VABS‐3), Behavior Rating Inventory of Executive Function – Preschool Version (BRIEF‐P), and Pediatric Evaluation of Disability Inventory (PEDI). Results Fifty‐eight children were enrolled, with 47% younger than age 2 years. At least 80% of children did not achieve age‐appropriate milestones. Mean BSID‐III Cognitive raw scores increased minimally, with age‐equivalent gains of only 3 months over 1.5 years. Mean Cognitive Composite scores declined significantly by Month 12 (from 81.6 to 72.2; change: –11.0, 95% confidence interval [CI]: −15.3 to −6.8), signaling a widening gap compared with neurotypical development. Executive function worsened, with mean BRIEF‐P Global Executive Composite T‐scores increasing by 3.2 points/year. For some participants, scores were 5 standard deviations (SD) above the normative mean, reflecting abilities profoundly below age expectations (bottom .00003% of the population). Adaptive functioning worsened, with mean VABS‐3 Adaptive Behavior Composite decreasing from 78.7 to 68.1 over 1.5 years (change: –9.0, 95% CI: −11.9 to −6.1) and greater decline among children <2 years at enrollment, with scores decreasing by ~15 points (1 SD). Over half of children >3 years could not remove clothing independently; and when placed on a toilet, 48% could not use it. Significance Infants and young children with SCN1A + DS show significant and progressive developmental slowing across several domains, highlighting urgent need for therapies to mitigate the devastating impact on individuals and families.

Introduction Due to rising incidence of Hepato-Pancreato-Biliary (HPB) malignancies and more effective therapies, there are increased survivors after curative surgery but little emphasis is placed on survivorship. This study aims to evaluate the value and yield of postoperative surveillance of surgically treated HPB cancer patients within a single surgeon’s practice. Methods A retrospective 1-year (2024) review identified 128 unique patients with prior surgical resection of a HPB malignancy undergoing active cancer surveillance by the surgical team. We excluded patients with benign indications for surgery or active cancer surveillance outside of the surgical team. Results Of these, 112 (87.5%) and 16 (12.5%) underwent pancreatic and hepatobiliary resection, respectively. Median follow up was 1.5 years from the index operation (IQR: 0.7-2.8 years). Pancreatic pathology was pancreatic adenocarcinoma (PDAC), neuroendocrine, or miscellaneous in 70, 25, and 9 patients, respectively. Hepatobiliary pathology was cholangiocarcinoma (CCA), metastatic colorectal cancer, or hepatocellular carcinoma in 16, 6, and 2 patients, respectively. We identified 12 (9.3%) patients who had findings during the study time period resulting in a repeat HPB surgery. In addition, we identified 12 (9.3%) patients who required referral to another department for additional medical, surgical, or interventional treatments. The remaining 104 (81.2%) patients had findings of either no disease recurrence or stable disease with continued surveillance as a recommendation. Conclusion This study underscores the value of cancer surveillance for HPB cancer patients, demonstrating a yield of nearly 20% of patients with findings requiring repeat surgical intervention or referral to other departments.

OBJECTIVE Surgical site infection (SSI) is a leading cause of morbidity following posterior spine surgery. The optimal choice of skin closure technique depending on patient- and procedure-specific characteristics remains to be elucidated. METHODS The Neurosurgery Enterprise Registry (NER) at Mayo Clinic was queried for patients who underwent posterior spine surgery from 2017 to 2023. Propensity matching was performed to match patients on the basis of the development of SSI and baseline characteristics, including age, sex, race, and comorbidities. Perioperative outcomes were analyzed using data from the NER and medical records. RESULTS A total of 18,842 cases of posterior spine surgery were identified in the NER, and SSI was observed in 154 cases (0.8%). Of these patients, 308 patients were included in the 1:1 propensity score–matched cohort analysis, with 154 patients included in each group. Sutures were used in 224 patients (72.7%) and staples in 84 patients (27.3%) (p < 0.01). Female patients comprised 45.1% of the sutures group and 46.4% of the staples group (p = 0.8). The mean ± SD age was 59.8 ± 15.4 years in the sutures group and 60.8 ± 11.9 years in the staples group (p = 0.6). Fusion was performed in 27.2% of patients in the sutures group and 44% in the staples group (p < 0.01). Multilevel fusion comprised 68.9% of fusion cases in the sutures group and 67.6% in the staples group (p = 0.8). Comorbidities, such as diabetes (p = 0.6), hypertension (p = 0.1), and the use of disease-modifying antirheumatic drugs (DMARDs) (p = 0.5) and immunosuppressants (p = 0.2), did not differ between groups. Univariate analysis performed in the propensity score–matched cohort showed that SSI was observed in 53.6% of patients in the sutures group and 40.5% in the staples group (p = 0.04). No significant differences were noted regarding 30-day (p = 0.3), 90-day (p = 0.2), and 1-year (p = 0.3) readmissions and 30-day (p = 0.7), 90-day (p = 0.8), and 1-year (p = 0.8) reoperations. On multivariable logistic regression, SSI was not significantly associated with the choice of skin closure technique (p = 0.3). CONCLUSIONS After adjustment for spinal fusion, number of fused levels, the use of immunosuppressants, and other risk factors, SSI development was not significantly associated with the use of sutures versus staples following posterior spine surgery in our institution. Additionally, no significant differences were observed regarding baseline characteristics and other perioperative outcomes. The authors’ analysis shows that skin closure technique did not significantly affect SSI rates and other outcomes in these patients.

We sought to characterize the long-term patency of various graft types in patients undergoing coronary artery bypass grafting. A comprehensive literature search identified 139 studies including 56,827 patients who underwent isolated coronary artery bypass grafting surgery. The mean patient age was 62 years (95% confidence interval: 60–63), and 80% (95% confidence interval: 79–82) were male. Patency outcomes were analyzed for each graft type, and parametric extrapolation was performed based on mean patency and mean follow-up time per conduit. The left internal mammary artery (LIMA) demonstrated the highest mean patency at 96% with a mean follow-up of 3.2 years, followed by the right internal mammary artery (RIMA) at 94% (2.8 years), gastroepiploic artery (GEA) at 93% (1.7 years), and radial artery (RA) at 89% (3.7 years). The saphenous vein graft had the lowest mean patency at 82% with a mean follow-up of 3.5 years. Extrapolated 20-year patency rates were 77% for LIMA, 64% for RIMA, 54% for RA, 42% for GEA, and 33% for saphenous vein graft. Arterial grafts demonstrated superior long-term patency compared to vein grafts. LIMA remains the primary conduit of choice, while RIMA, followed by RA and GEA, may be appropriate secondary arterial conduits depending on patient-specific factors. Vein grafts had the poorest long-term patency.

Importance The introduction of immune checkpoint inhibitor (ICI) therapy has improved cancer outcomes but at the cost of adverse events, mainly related to the immune system. Cardiovascular (CV) toxic effects, and especially myocarditis, are of particular concern and are the subject of this position statement by the International Cardio-Oncology Society with representation of experts from oncology, hematology, and cardiology. Observations CV toxic effects of ICI therapies include inflammation-associated diseases, such as myocarditis, pericarditis, and vasculitis, as well as the aggravation of chronic inflammatory conditions, such as atherosclerosis with acute ischemic complications (myocardial infarction and stroke). Patients taking ICI therapies can also develop cardiac dysfunction, stress-induced cardiomyopathy (Takotsubo or apical ballooning syndrome), and heart failure without inflammatory cell infiltration of the myocardium. Atrial and ventricular arrhythmias can emerge in the setting of a systemic inflammatory milieu, myocarditis, or ischemia. Of all potential CV adverse effects, myocarditis remains of highest concern, although fatality rates have declined over time with a broadening spectrum of presentations ranging from troponin elevation of uncertain significance to smoldering, nonsevere, and severe or fulminant myocarditis. Conclusions and Relevance Concerns for myocarditis continue to dominate the spectrum of CV toxic effects in patients receiving ICI therapy. Recommendations for management vary according to severity. Multidisciplinary collaborations remain key for managing acute toxic effects and future cancer treatment decisions, including ICI rechallenge. Ischemic heart disease constitutes the main differential diagnosis in these patients, while pericarditis can be concomitantly present, and atrial and ventricular arrhythmias can also complicate the clinical picture. Several gaps in knowledge are identified and require further research.

Objective: To characterize patient outcomes after primary stereotactic radiosurgery (SRS) for the management of sporadic facial nerve schwannoma. Study design: Retrospective cohort study. Setting: Six tertiary referral centers across the United States and United Kingdom. Patients: Adults undergoing SRS from 2000 through 2023 for sporadic facial nerve schwannoma along any segment of the facial nerve were included. Patients with NF2-related schwannomatosis were excluded. Intervention: Stereotactic radiosurgery. Main outcome measure: Long-term tumor control. Results: Among 60 patients meeting inclusion, the median age at SRS was 52 years (IQR: 41 to 64) with a median tumor size of 19.5 mm (IQR: 14.7 to 22.8). Tumors commonly involved the internal auditory canal (73%), cisternal (49%), geniculate/labyrinthine (47%), and tympanic segments (22%). Two patients experienced SRS failure and underwent salvage treatment; salvage-free survival rates (95% CI; number still at risk) at 1, 3, 5, and 10 years after SRS were 100% (100 to 100; 55), 100% (100 to 100; 36), 100% (100 to 100; 18), and 87% (72 to 100; 9), respectively. Among 31 (52%) patients with House-Brackmann (HB) grade I facial function at presentation, only 6 demonstrated worse facial function at a median of 3.2 years (IQR: 1.7 to 6.6) after SRS. Of 18 patients with serviceable hearing (AAO-HNS class A/B) at SRS, 13 maintained serviceable hearing at a median of 1.0 years (IQR: 0.5 to 4.9) of post-SRS audiometric follow-up. Conclusions: Durable tumor control after primary SRS for sporadic facial nerve schwannoma is achieved in most patients. Among those with HB grade I facial function at presentation, treatment with SRS harbors limited additional risk of facial paresis beyond observation alone.

Importance Total pancreatectomy (TP) is indicated for advanced pancreatic cancer or multifocal tumors. Furthermore, TP may be performed to avoid the risk of pancreatic fistula in selected patients to improve the perioperative risk profile. Objective To define reference values for TP based on a low-risk cohort treated at expert centers. Design, Setting, and Participants This multicenter study analyzed outcomes from patients undergoing primary TP for malignant or benign lesions from 25 international expert centers from January 2017 to November 2023. Low-risk patients undergoing TP (LR-TP) were without vascular resections or significant comorbidities. Exposures TP. Main Outcomes and Measures Twenty reference values were derived from the 75th or the 25th percentile of the median values of all centers. Outcomes of LR-TP were compared with a cohort of TP with vascular resection, TP due to high-risk pancreatic anastomosis, and the benchmark values for low-risk pancreatoduodenectomy. Results Of 994 patients, 333 (33.5%; median [IQR] age, 66 [58-72] years; 171 male [51.4%]) qualified as the LR-TP cohort. Reference values included blood loss (≤1000 mL), major complications (≤37%), 3-month postoperative mortality (&amp;lt;6%), and retrieved lymph nodes (≥29). Compared with TP with vascular resections, reference cutoffs were not met for major complications (51% vs LR-TP ≤37%) and 90-day mortality (11% vs LR-TP ≤6%). For TP due to high-risk anastomosis, failure to rescue rate (38% vs ≤6%) and 90-day mortality (11% vs LR-TP ≤6%) were not met. Compared with pancreatoduodenectomy, reference values for postoperative mortality were 3 times higher for LR-TP (≤2% vs ≤6%) and less for resected lymph nodes (≥16 vs ≥29). Conclusions and Relevance This case-control study provided global reference values for TP, indicating significantly higher postoperative morbidity and mortality compared with pancreatoduodenectomy. Perioperative morbidity of TP was especially increased in patients with vascular resections. These reference values can serve for quality control of pancreatic surgery.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that increases risk for premature coronary artery disease and has accessible and effective interventions. The Dutch lipid clinic network is currently the most used diagnostic criterion; however, genetic sequencing provides a definitive diagnosis of FH. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify individuals who were genotype positive for FH. METHODS: Participants were recruited from 3 geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; and Jacksonville, FL). Participants underwent Exome+ sequencing (dba Helix, San Mateo, CA) and return of results for specific genetic findings in APOB , LDLR , or PCSK9 . A chart review was performed to collect demographics, personal, and family cardiovascular history. RESULTS: At the time of the study, 84 413 participants were enrolled in the Tapestry study. Annotation and interpretation of all variants in genes for FH resulted in the identification of 419 likely pathogenic and pathogenic variants (prevalence, 0.50%), which included 116 APOB , 298 LDLR , and 5 PCSK9 . Sixty-six percent were female, the mean body mass index was 27.3, with 12.3% reporting a history of diabetes. Hypertriglyceridemia (≥150 mg/dL) was present in 39.5% and reduced HDL (<50 mg/dL) was present in 56.7% of patients. 27.5% of patients were not on cholesterol-lowering medications, and only 10% of FH carriers were at goal low-density lipoprotein cholesterol levels. A history of coronary artery disease was reported in 22.4% of the cohort. Nearly 90% of these participants were newly diagnosed carriers of FH. Only 30.8% of confirmed genetic diagnoses of FH satisfied clinical (Dutch lipid clinic network) criteria for a diagnosis. CONCLUSIONS: Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have familial hypercholesterolemia. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05212428.