Molecular and Clinicopathologic Characterization of Mismatch Repair-Deficient Endometrial Carcinoma Not Related to MLH1 Promoter Hypermethylation.

Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV). In cases where these are not detected, emerging evidence highlights the significance of double-somatic MMR gene alterations as a sporadic cause of MMRd, alongside POLE/POLD1 exonuclease domain (EDM) PV leading to secondary MMR PV. Our understanding of the incidence of different MMRd EC origins not related to MLH1-PHM, their associations with clinicopathologic characteristics, and the prognostic implications remains limited. In a combined analysis of the PORTEC-1, -2, and -3 trials (n = 1254), 84 MMRd EC not related to MLH1-PHM were identified that successfully underwent paired tumor-normal tissue next-generation sequencing of the MMR and POLE/POLD1 genes. Among these, 37% were LS associated (LS-MMRd EC), 38% were due to double-somatic hits (DS-MMRd EC), and 25% remained unexplained. LS-MMRd EC exhibited higher rates of MSH6 (52% vs 19%) or PMS2 loss (29% vs 3%) than DS-MMRd EC, and exclusively showed MMR-deficient gland foci. DS-MMRd EC had higher rates of combined MSH2/MSH6 loss (47% vs 16%), loss of >2 MMR proteins (16% vs 3%), and somatic POLE-EDM PV (25% vs 3%) than LS-MMRd EC. Clinicopathologic characteristics, including age at tumor onset and prognosis, did not differ among the various groups. Our study validates the use of paired tumor-normal next-generation sequencing to identify definitive sporadic causes in MMRd EC unrelated to MLH1-PHM. MMR immunohistochemistry and POLE-EDM mutation status can aid in the differentiation between LS-MMRd EC and DS-MMRd EC. These findings emphasize the need for integrating tumor sequencing into LS diagnostics, along with clear interpretation guidelines, to improve clinical management. Although not impacting prognosis, confirmation of DS-MMRd EC may release patients and relatives from burdensome LS surveillance.

The Impact of Parent-Based Support Programs on Neurodevelopmental Prognosis: Second-Year Results from a Newly Established Neurodevelopmental Follow-Up Unit in a Tertiary Hospital.

This study aims to assess the neurodevelopmental progress of high-risk infants 2 years post implementation of the Neurodevelopmental Follow-Up Unit (NFU) program at our hospital and explore implementation challenges for insights. Infants were assessed using the Hammersmith Infant Neurological Examination (HINE), The Alberta Infant Motor Scale (AIMS), and Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). A multidisciplinary team provided comprehensive parent education covering neurologic cues, postural advice, and developmental instructions in accordance with the children's assessment findings. In addition, a pediatric physical therapist provided motor development training emphasizing age-appropriate milestones and functional independence, while child development specialists addressed delays identified through BSID-III assessments. A total of 121 high-risk babies were enrolled during a 2-year period. Results revealed that 9 infants exhibited suboptimal HINE scores at 3-4 months, with only 2 maintaining suboptimal scores at 12-15 months. Similarly, 2 infants with suboptimal AIMS scores at 3-4 months reached normal values at 12-15 months. Comparable improvements were observed in BSID-III scores. While no correlation between HINE and AIMS scores was found at the 3-4-month mark, a significant correlation emerged between AIMS and HINE scores at 6-9 months (r = 0.643, P < .001) and 12-15 months (r = 0.820, P < .001). Encouraging early family education alongside regular monitoring of high-risk newborns appears to have a positive impact on their motor and cognitive development. Consideration of clinical recommendations, such as tailored interventions and periodic assessments, may contribute to optimizing developmental outcomes.

Role of Preoperative Embolization in Surgical Management of Carotid Body Tumors: A Systematic Review and Meta-Analysis.

The objective of this study is to evaluate the effect of preoperative embolization on carotid body tumor resection. A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Scopus, and Web of Science were screened for studies published between 2010 and 2022. Primary outcomes investigated were intraoperative blood loss, operative time, length of hospital stay, and perioperative complications such as transient ischemic attack (TIA)/stroke, vascular injury, and cranial nerve injury (CNI). A random effects model was used in cases where study heterogeneity was high. Overall, 25 studies were included in the systematic review, involving 1649 patients: 23 studies were eligible for meta-analysis. The incidence of vascular injury was significantly less in the preoperative embolization group (odds ratio (OR) = 0.60; 95% CI: 0.42-0.84; P = .003). There was no statistically significant difference between the two groups regarding intraoperative blood loss, operative time, length of hospital stay, incidence of TIA/stroke, and CNI. Subgroup analyses did not demonstrate significant difference between Shamblin I, II, and III subgroups regarding operative time. This meta-analysis found preoperative embolization to be significantly beneficial in reducing incidence of vascular injury.