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Objective: Evaluate patient-reported symptoms and quality of life (QOL) before and after female sterilization device (Essure) removal. Design: Multicenter prospective study. Setting: Three academic institutions. Population or Sample: Patients with device-attributed symptoms undergoing Essure removal. Methods: Symptoms were measured using a study-specific questionnaire and Short Form-8 (divided into Physical and Mental Component Scores). Scores at 4 months postoperative were compared to baseline using a mixed effects logistic regression and linear mixed model. Subgroup analysis was performed for hysterectomy and uterine-preserving groups. Main Outcome Measures: Patient-reported symptoms and Short Form-8 4 months after Essure removal compared to baseline. Results: A total of 80 patients enrolled in the study and underwent Essure removal: 53 (66.3%) with laparoscopic hysterectomy and 27 (33.8%) with laparoscopic bilateral salpingectomy or bilateral cornuectomy. Fifty-one participants (63.8%) completed the 4-month postoperative questionnaire. Of the 17 device-attributed symptoms evaluated, participants reported clinically important improvement in 16 of the symptoms postoperatively. QOL improved significantly following device removal, with the Physical Component Score improving by 9.9 points (95% CI: 7.0–12.9) and the Mental Component Score by 13.8 points (95% CI: 10.4–17.2). QOL improved in both physical and mental score domains after device removal with no difference between hysterectomy and uterine-preserving groups ( p = 0.83 and p = 0.06, respectively). Of the entire cohort, 92.2% ( n = 47) were satisfied with their surgical results. Conclusions: Patients undergoing Essure removal for device-attributed symptoms report improved symptoms and QOL following surgery. Device removal may benefit those experiencing device-attributed symptoms and is associated with high patient satisfaction.

BACKGROUND AND OBJECTIVES: It is not clear whether changes in lesion volume might represent a clinically relevant and statistically advantageous outcome parameter in early phase trials aimed at preventing bleeding in cerebral cavernous malformations (CCM). METHODS: We examined prospective changes in CCM lesion volume in the double-blinded AT CASH EPOC trial (clinicaltrials.gov NCT02603328). We correlated these with symptomatic hemorrhage (SH) events, contemporaneously assessed changes in lesional iron content by quantitative susceptibility mapping (QSM) on MRI, and objective (modified Rankin Scale (mRS)) and subjective (Euro-QoL Visual Analog Scale [EQ-VAS]) functional status. We also simulated sample sizes needed to detect potential effects on lesion volume. RESULTS: There was excellent correlation between independently assessed maximum lesion diameter and CCM lesion volume (R 2 = 0.68, P < .0001). The mean (SD) percentage change in lesion volume per year was +6 (65) and +18 (94) in atorvastatin and placebo patients, respectively ( P = .43). All cases with SH had increases in lesion volume and increases in mean lesional iron content by QSM, and most had declines in functional status on mRS and EQ-VAS, but there were no overall meaningful correlations of changes in lesion volume with concomitant changes in mean lesional QSM, mRS, or EQ-VAS (all R/R 2 < 0.5 and Bonferroni corrected P > .05), including in brainstem lesions analyzed separately. Sample size simulations indicate larger case numbers needed to demonstrate an effect on change in lesion volume than those needed to detect an effect on QSM change with α = 0.05 and β = 0.8, and even larger samples to detect effects on the number of cases with increased or decreased lesion volume. CONCLUSION: Changes in lesion volume occur frequently in CCM lesions after recent SH, but do not correlate with biomarkers of lesional bleeding, nor reflect functional changes, and are not statistically advantageous compared with QSM measures in detecting potential drug effects.

ABSTRACT The World Health Organization (WHO) 5th Edition and International Consensus Classification (ICC) have continued to delineate more genetically defined acute leukemias. Both recognize genetic aberrations associated with myelodysplastic syndromes/neoplasms (MDS) as defining MDS‐related AML (AML‐MR). Mutations in RUNX1 are included in this category in the ICC, but not WHO. The current classifications are unclear on how acute leukemias with ambiguous lineage (ALAL), including those of mixed lineage (MPAL) and those without a defined lineage (AUL), should be categorized in the presence of such mutations. Our multi‐institutional study aims to determine the significance of RUNX1 mutation in ALAL compared to de novo AML. Newly diagnosed MPAL, AUL, and AML with RUNX1 mutations were collected. ALAL with MDS‐related cytogenetics, BCR::ABL1 , KMT2A rearrangements, or ZNF384 or BCL11b abnormalities were excluded. We analyzed 17 cases of ALAL and 71 cases of AML that met inclusion criteria. ALAL‐ RUNX1 and AML‐ RUNX1 showed overlapping mutational landscapes with frequent comutations in MDS‐associated genes. No ALAL‐ RUNX1 or AML‐ RUNX1 cases showed concomitant TP53 mutation. ALAL‐ RUNX1 had more bone marrow blasts and more karyotypic abnormalities; however, neither impacted survival, nor did RUNX1 variant allele frequency (VAF). Survival analysis revealed similarly poor outcomes between them. AML‐directed therapies and allogeneic hematopoietic stem cell transplant trended toward improved survival in ALAL‐ RUNX1; however, it did not reach significance. Our results suggest ALAL‐ RUNX1 is associated with younger age, higher blasts, and more karyotypic abnormalities, but has similar clinical and genetic features and outcomes to AML‐ RUNX1 . Our findings suggest, like other MR mutations, RUNX1 ‐mutated ALALs should be included within AML‐MR.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of postthymic T cell neoplasms, with ~40% classified as PTCL–not otherwise specified (PTCL-NOS). PTCL-GATA3, a molecularly defined subtype, associated with T helper 2 (T H 2)–like differentiation and poor prognosis, has frequent co-occurrence of TP53 loss/mutation and heterozygous PTEN loss. CD4+ T cell conditional mouse models with Trp53 mutation/deletion and Pten loss demonstrated mature T cell lymphomas (mTCLs) with T H 2-like transcriptomic and immunophenotypic profiles. Molecular studies revealed that codeletion of Trp53/Pten induced T cell receptor and Janus kinase–signal transducer and activator of transcription signaling, promoting T H 2 differentiation while inhibiting T H 1 differentiation. These findings were validated by CRISPR editing of TP53/PTEN loss in human CD4+ T cells and mechanistically evaluated the p53 binding region in intron-3 of GATA3, resulting in transcriptional repression. Transcriptomic profiles of m-TCLs recapitulated human-PTCL-GATA3 transcriptome and distinguished PTCL-NOS subtypes. Preclinical assessment of m-TCLs with PI3Kγ/δ inhibitors significantly improved survival, supporting a therapeutic approach for the p53-aberrant PTCL-GATA3.

BACKGROUND AND OBJECTIVES: The Management of Myelomeningocele Study established a role for maternal-fetal surgery for myelomeningocele (MMC) but was limited to patients with a maternal body mass index (BMI) less than 35 kg/m 2 . However, as the rate of obesity has increased globally, some centers have extended the Management of Myelomeningocele Study criteria to include patients with a BMI of 35 to 40 kg/m 2 . We used the Fetal MMC Consortium registry to analyze the complications associated with maternal-fetal surgery in patients with a maternal BMI < 35 kg/m 2 compared with 35 to 40 kg/m 2 . METHODS: The prospective observational Fetal MMC Consortium registry sponsored by the North American Fetal Therapy Network was used to extract deidentified “maternal complication” and “fetal/neonatal complication” data sets, corresponding to patients with complete entries related to maternal or fetal/neonatal complications, respectively. Demographics, clinical characteristics, and complications were recorded. Propensity score matching was conducted with a 2:1 algorithm, and outcomes were compared between patients with BMI < 35 kg/m 2 and those with BMI 35 to 40 kg/m 2 . RESULTS: Propensity score matching resulted in 156 patients with BMI < 35 kg/m 2 and 78 patients with BMI 35 to 40 kg/m 2 in the “maternal complication” data set, and 130 patients with BMI < 35 kg/m 2 and 65 patients with BMI 35 to 40 kg/m 2 in the “fetal/neonatal complication” data set. No significant differences in the median number of maternal (2.0 vs 2.0; P = .257) or median number of fetal/neonatal (1.0 vs 1.0; P = .409) complications were observed between the 2 cohorts. Furthermore, prematurity rates did not differ significantly between the BMI < 35 and BMI 35 to 40 cohorts. CONCLUSION: Maternal-fetal surgery for open neural tube defect closure is not associated with increased risks among patients with a maternal BMI of 35 to 40 kg/m 2 . Extending the initial inclusion criteria for prenatal MMC closure has the potential to expand access to patients with a higher risk for open neural tube defects.

Background. Living kidney donation (KD) evaluation particularly focuses on glomerular filtration rate (GFR). Assessing GFR in living kidney donors can be done by estimation (eGFR) or measurement (mGFR). This study aims to evaluate the impact of eGFR equations, focusing on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation for donor eligibility screening and the reclassification of donors excluded by eGFR criteria to mGFR assessments. Methods. Retrospective, single-center observational study of 2512 kidney donors evaluated between 2011 and 2023, at the Mayo Clinic. We performed analyses and comparisons of 4 eGFR formulae and 2 mGFR methods in terms of performance, eligibility criteria according to Kidney Disease: Improving Global Outcomes guidelines/age-adjusted criteria, eligibility reclassification, and subgroup analyses. Results. The CKD-EPI 2021 resulted in a higher percentage of patients being eligible for KD (81.4%) and achieved the highest P10 (32%–34%) and P30 (87%–88%) across all mGFR methods. When patients were deemed eligible for donation by any eGFR formula, 95% retained this status on reassessment with mGFR. Conversely, when an eGFR formula classified a patient as ineligible, this was revised to be eligible in about 90% of cases on reassessment with mGFR, with a higher reclassification rate observed when the IoCl was used instead of CrCl. Conclusions. The CKD-EPI 2021 performs best for screening potential KD. If a KD is deemed ineligible by CKD-EPI 2021, there is a high likelihood that they will be reclassified as eligible when assessed with mGFR. This study strongly supports using mGFR in donor evaluations, especially when the eGFR does not meet the criteria to ensure equity of access to being a living donor.