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PURPOSE Lung cancer remains a leading cause of cancer mortality in Brazil, with non–small cell lung cancer (NSCLC) accounting for 85% of cases, with 1.6% carrying epidermal growth factor receptor (EGFR) exon 20 mutations. In the phase I CHRYSALIS trial (ClinicalTrials.gov identifier: NCT02609776 ), amivantamab demonstrated a median overall survival (OS) of 22.8 months versus 8.3 months with docetaxel, the standard second-line Brazil's Unified Health System (SUS) therapy. Although the Brazilian Health Regulatory Agency approved amivantamab, the National Commission for the Incorporation of Technologies’ cost-effectiveness reviews result in an average 10-year delay before SUS incorporation. We aimed to estimate premature deaths and life-years lost attributable to this access gap. METHODS Using National Institute of Cancer (INCA) data, we estimated SUS-eligible patients, NSCLC prevalence, and EGFR exon 20 frequency. Stage distribution and 5-year recurrence rates identify candidates for amivantamab. A hazard ratio (HR) was derived from the inverse exponential method (ln(2)/OS ratio). Preventable deaths were calculated as: eligible patients × (1 – HR). Life-years gained per patient were estimated as OS difference. RESULTS Of the 26,548 new patients with lung cancer, 18,973 are SUS-eligible, 16,127 have NSCLC, and 258 have EGFR exon 20 mutations. Metastatic disease accounts for 114, whereas recurrences occur in 60 (stage III), eight (II), and four (I), totaling 186 candidates annually. With an HR of 0.364, the annual preventable death in the base-case scenario is equal to 186 × (1 – 0.364) × 95% = 112 patients. Over 10 years, 1,120 premature deaths and 1,353 life-years could be avoided. CONCLUSION Delayed SUS incorporation of amivantamab may result in over a 1,000 preventable deaths and life-years lost among Brazilian EGFR exon 20–mutated NSCLC. Urgent real-world studies and cost-effectiveness analyses are needed.

SUDEP risk is influenced by longevity genomics: A polygenic risk score study Martins H, Mills JD, Pagni S, Gulcebi MI, Vakrinou A, Moloney PB, Clayton LM, Bellampalli R, Stamberger H, Weckhuysen S, Striano P, Zara F, Bagnall RD, Harris RV, Lawrence KM, Sadleir LG, Crompton DE, Friedman D, Laze J, Li L, Berkovic SF, Semsarian C, Scheffer IE, Devinsky O, Kuchenbaecker K, Balestrini S, Sisodiya SM. EBioMedicine. 2025 Aug;118:105841. doi: 10.1016/j.ebiom.2025.105841. Epub 2025 Jul 28. PMID: 40731221; PMCID: PMC12368338. Background: Sudden Unexpected Death in Epilepsy (SUDEP) is a rare and tragic outcome in epilepsy, identified by those with the condition as their most serious concern. Although several clinical factors are associated with elevated SUDEP risk, mechanisms underlying SUDEP are poorly understood, making individual risk prediction challenging, especially early in the disease course. We hypothesised that common genetic variation contributes to SUDEP risk. Methods: Genetic data from people who had succumbed to SUDEP was compared to data from people with epilepsy who had not succumbed to SUDEP and from healthy controls. Polygenic risk scores (PRSs) for longevity, intelligence and epilepsy were compared across cohorts. Reactome pathways and gene ontology terms implicated by the contributing single nucleotide polymorphisms (SNPs) were explored. In the subset of SUDEP cases with the necessary data available, a risk score was calculated using an existing risk prediction tool (SUDEP-3); the added value to this prediction of SNP-based genomic information was evaluated. Findings: Only European-ancestry participants were included. 161 SUDEP cases were compared to 768 cases with epilepsy and 1153 healthy controls. PRS for longevity was significantly reduced in SUDEP cases compared to disease (P =0.0096) and healthy controls (P=0.0016), as was PRS for intelligence (SUDEP cases compared to disease (P=0.0073) and healthy controls (P=0.00024)). The PRS for epilepsy did not differ between SUDEP cases and disease controls (P =0.76). SNP-determined pathway and gene ontology analysis highlighted those related to inter-neuronal communication as amongst the most enriched in SUDEP. Addition of PRS for longevity and intelligence to SUDEP-3 scores improved risk prediction in a subset of cases (38) and controls (703), raising the area-under-the-curve in a receiver-operator characteristic from 0·699 using SUDEP-3 alone to 0·913 when PRSs were added. Interpretation: Common genetic variation contributes to SUDEP risk, offering new approaches to improve risk prediction and to understand underlying mechanisms.

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.

Phonoenterography (PEG) offers a non-invasive and radiation-free technique to assess gastrointestinal activity through acoustic signal analysis. In this feasibility study, 110 high-resolution PEG recordings (44.1 kHz, 16-bit) were acquired from eight healthy individuals, yielding 6314 prominent bowel sound (PBS) segments through automated segmentation. Each event was characterized using a 279-feature acoustic profile comprising Mel-frequency cepstral coefficients (MFCCs), their first-order derivatives (Δ-MFCCs), and six global spectral parameters. After normalization and dimensionality reduction with PCA and UMAP (cosine distance, 35 neighbors, minimum distance = 0.01), five clustering strategies were evaluated. K-Means (k = 5) achieved the most favorable balance between cluster quality (silhouette = 0.60; Calinski–Harabasz = 19,165; Davies–Bouldin = 0.68) and interpretability, consistently identifying five acoustic patterns: single-burst, multiple-burst, harmonic, random-continuous, and multi-modal. Temporal modeling of clustered events further revealed distinct sequential dynamics, with Single-Burst events showing the longest dwell times, random continuous the shortest, and strong diagonal elements in the transition matrix confirming measurable state persistence. Frequent transitions between random continuous and multi-modal states suggested dynamic exchanges between transient and overlapping motility patterns. Together, these findings demonstrate that unsupervised PEG-based analysis can capture both acoustic variability and temporal organization of bowel sounds. This annotation-free approach provides a scalable framework for real-time gastrointestinal monitoring and holds potential for clinical translation in conditions such as postoperative ileus, bowel obstruction, irritable bowel syndrome, and inflammatory bowel disease.

Background: Achieving active elbow flexion in children with amyoplasia can greatly improve independence in activities of daily living. This study investigated long-term outcomes of the long head triceps transfer procedure performed for that purpose. Methods: A retrospective review of medical records was performed for all patients with amyoplasia who underwent a long head triceps transfer between January 1, 2008 and December 31, 2019. Patients with follow-up of less than 2 years were excluded. Pre- and postoperative range of motion were recorded, and patient-reported outcome measures included a visual analog scale (VAS) for function (scale 0 to 10), a VAS for overall satisfaction (scale 0 to 10), and the Pediatric Outcomes Data Collection Instrument (PODCI). Pre- and postoperative motion were compared via paired t tests. Results: Seventeen patients (25 extremities) were included. Postoperatively, average active elbow flexion was 78 degrees against gravity and 90 degrees with gravity eliminated. Patients with active elevation of the shoulder ≥90 degrees showed average active elbow flexion with gravity eliminated of 85 degrees. The mean VAS score for improvement of function was 8.3 (range, 4 to 10) from parents and 9.0 (range, 8 to 10) from patients older than 10 years. The mean VAS scores for overall satisfaction were 8.0 (range, 5 to 10) and 8.1 (range, 6 to 10), respectively. Mean PODCI scores ranged from 63 to 73 for upper extremity, 83 to 76 for transfer and basic mobility, 64 to 73 for sports participation, 83 to 95 for pain and comfort, 90 to 97 for happiness, and 74 to 79 for global function. Conclusions: The long head of the triceps transfer is an effective treatment modality for patients with amyoplasia who present with absent active elbow flexion, good passive elbow flexion, and well-defined long head and lateral heads of the triceps muscle. Overall, patients gained an active range of elbow motion with no significant functional elbow contracture and improved quality of life. However, patients with a history of elbow release surgery are at higher risk of flexion contracture and should be screened especially carefully. Level of Evidence: Level IV—case series