Women with germline pathogenic variants (GPV) in BRCA1/2, PALB2, or other high penetrance genes may consider risk reducing mastectomy (RRM) with or without reconstruction to reduce their risk of developing breast cancer. Few studies have characterized reconstructive trends in this patient population. We conducted a retrospective cohort study of female patients with a confirmed GPV in a high penetrance breast cancer susceptibility gene who underwent RRM between 2003 and 2024. Clinicodemographic and surgical data were extracted from the electronic medical record. The Chi-squared test and Mantel-Haenszel test for trend were used to evaluate factors and temporal trends associated with reconstruction. Of 443 female GPV carriers who underwent RRM, 394 (88.9
The posterior fossa is a critical anatomical region housing the cerebellum and brainstem. Posterior fossa malformations are a heterogeneous group of conditions challenging to diagnose and prognosticate prenatally. Fetal magnetic resonance imaging (MRI) plays an important role in their assessment. This retrospective study examined the clinical and radiological data from 115 maternal-fetal dyads (116 fetuses) with posterior fossa malformations on fetal MRI, assessed concordance with postnatal imaging, and investigated MRI features associated with adverse outcomes. Fetal posterior fossa malformations were heterogenous: 66% (76/116) were structural and 34% (40/116) involved only CSF-containing lesions. Cerebellar hypoplasia was the most frequent posterior fossa malformation, observed in 33% (38/116). 78% (91/116) of posterior fossa malformations were "complex" (with additional central nervous system and/or extraneural anomalies). Concordance between fetal MRI and postnatal imaging was 51% (27/53), which improved to 69% (20/29) when CSF-containing lesions were excluded. Among terminated pregnancies who underwent autopsy, the fetal MRI diagnosis was confirmed in 75% (12/16). Chiari-II malformations, pontocerebellar hypoplasia and cerebellar asymmetry were consistently confirmed on postnatal imaging. Four fetuses with cerebellar hypoplasia had normal postnatal imaging. Structural and "complex" posterior fossa malformations were more likely to have poor pregnancy outcomes (i.e., termination, fetal demise, or neonatal death) than CSF-only and isolated anomalies. Genetic testing was positive in 24% (19/80) of tested cases, and 16% (19/116) of the overall cohort. Fetal MRI has an important role in the accurate diagnosis and management of posterior fossa malformations, particularly for structural anomalies which are associated with poor pregnancy outcomes.
Importance:The age-adjusted D-dimer cutoff (age × 10 µg/L in patients 50 years or older), safely increases the diagnostic yield of D-dimer in patients with suspected pulmonary embolism but has not been validated in patients with suspected leg deep vein thrombosis (DVT). Objective:To prospectively validate whether using an age-adjusted D-dimer cutoff allows clinicians to safely rule out DVT. Design, Setting, and Patients:Multicenter, multinational prospective management outcome study conducted in 27 centers in Belgium, Canada, France, and Switzerland between January 2015 and October 2022 (last follow-up visit, January 30, 2023) and including outpatients presenting to the emergency department with suspected DVT. Interventions:Patients were assessed by a sequential diagnostic strategy based on the assessment of clinical pretest probability by the Wells score, a highly sensitive D-dimer test, and leg compression ultrasonography. Patients in whom DVT was ruled out were followed up for a 3-month period. Main Outcome and Measure:The primary outcome was the rate of adjudicated symptomatic venous thromboembolic events during follow-up in patients in whom DVT was ruled out based on a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff. Results:A total of 3205 patients were included. Median age was 59 years, and 1737 (54%) were female. DVT prevalence was 14%. Among the 2169 patients with a non-high or unlikely clinical probability, 531 (24.5% [95% CI, 22.7%-26.4%]) had a D-dimer level less than 500 µg/L, and 161 additional patients (7.4% [95% CI, 6.4%-8.6%]) had a D-dimer level between 500 µg/L and their age-adjusted cutoff. No failures were identified in patients with a D-dimer level 500 µg/L or greater but below the age-adjusted cutoff (0% [95% CI, 0%-2.3%]). Among patients 75 years or older, using the age-adjusted cutoff instead of the 500-µg/L cutoff increased the proportion of negative D-dimer from 33 of 379 (8.7% [95% CI, 6.3%-12.0%]) to 99 of 379 (26.1% [95% CI, 22.0%-30.8%]), without any false-negative test results. Conclusions and Relevance:The age-adjusted D-dimer cutoff may safely rule out DVT and was associated with a larger number of patients in whom DVT could be effectively ruled out. Trial Registration:ClinicalTrials.gov Identifier: NCT02384135.
Endocrine prevention is a well-established preventative strategy for women with high-risk lesions (HRL). The objective of the study was to evaluate factors associated with endocrine prevention adherence in this patient population. We performed a retrospective cohort study of all women referred for atypical ductal and lobular hyperplasia (ADH/ALH) and lobular carcinoma in situ (LCIS) between 2019 and 2025. Data pertaining to eligibility, initiation, and adherence to endocrine prevention were extracted with univariate analyses performed to evaluate factors associated with adherence. Among 200 female patients with HRL, 112 (56
The treatment of patients with PNH has been revolutionized by terminal complement C5 inhibitors, which control intravascular hemolysis and thrombosis, reduce morbidity and mortality, and improve life expectancy to that approaching people without PNH. In recent years, approval of proximal inhibitors provides clinicians and patients with additional treatment options such that patients who have residual anemia, ongoing symptoms affecting quality of life, or are intolerant to terminal C5 inhibition now have options to optimize treatment. Here, we provide five questions to guide clinicians involved in the care of patients with PNH in assessing treatment response on terminal inhibitors and identifying patients who might benefit from therapy adjustments. We also provide insights into additional treatment options.
