Purpose Dyspareunia is common in breast cancer survivors because of low estrogen. This study explored whether dyspareunia is introital pain, preventable with analgesic liquid. Patients and Methods In a randomized, controlled, double-blind trial, estrogen-deficient breast cancer survivors with severe penetrative dyspareunia applied either saline or 4% aqueous lidocaine to the vulvar vestibule for 3 minutes before vaginal penetration. After a 1-month blinded trial of patient-assessed twice-per-week tampon insertion or intercourse, all patients received lidocaine for 2 months in an open-label trial. The primary outcome was patient-related assessment of penetration pain on a scale of zero to 10. Secondary outcomes were sexual distress (Female Sexual Distress Scale), sexual function (Sexual Function Questionnaire), and resumption of intercourse. Comparisons were made with the Mann-Whitney U and Wilcoxon signed rank test with significance set at P < .05. Results In all, 46 patients, screened to exclude those with pelvic muscle and organ pain, uniformly had clinical evidence of severe vulvovaginal atrophy, dyspareunia (median pain score, 8 of 10; interquartile range [IQR], 7 to 9), increased sexual distress scores (median, 30.5; IQR, 23 to 37; abnormal, > 11), and abnormal sexual function. Users of lidocaine reported less pain during intercourse in the blinded phase (median score of 1.0 compared with saline score of 5.3; P = .007). After open-label lidocaine use, 37 (90%) of 41 reported comfortable penetration. Sexual distress decreased (median score, 14; IQR, 3 to 20; P < .001), and sexual function improved in all but one domain. Of 20 prior abstainers from intercourse who completed the study, 17 (85%) had resumed comfortable penetrative intimacy. No partners reported penile numbness. Conclusion Breast cancer survivors with menopausal dyspareunia can have comfortable intercourse after applying liquid lidocaine compresses to the vulvar vestibule before penetration.

In acute myeloid leukemia (AML), the assessment of post‐treatment minimal residual disease (MRD) may inform a more effective management approach. We investigated the prognostic utility of next‐generation sequencing (NGS)‐based MRD detection undertaken before hematopoietic stem cell transplantation (HSCT). Forty‐two AML subjects underwent serial disease monitoring both by standard methods, and a targeted 42‐gene NGS assay, able to detect leukemia‐specific mutant alleles (with >0.5% VAF) (mean 5.1 samples per subject). The prognostic relevance of any persisting diagnostic mutation before transplant (≤27 days) was assessed during 22.1 months (median) of post‐transplant follow‐up. The sensitivity of the NGS assay (27 MRD‐positive subjects) exceeded that of the non‐molecular methods (morphology, FISH, and flow cytometry) (11 positive subjects). Only one of the 13 subjects who relapsed after HSCT was NGS MRD‐negative (92% assay sensitivity). The cumulative incidence of post‐transplant leukemic relapse was significantly higher in the pre‐transplant NGS MRD‐positive (vs MRD‐negative) subjects (P = .014). After adjusting for TP53 mutation and transplant conditioning regimen, NGS MRD‐positivity retained independent prognostic significance for leukemic relapse (subdistribution hazard ratio = 7.3; P = .05). The pre‐transplant NGS MRD‐positive subjects also had significantly shortened progression‐free survival (P = .038), and marginally shortened overall survival (P = .068). In patients with AML undergoing HSCT, the pre‐transplant persistence of NGS‐defined MRD imparts a significant, sensitive, strong, and independent increased risk for subsequent leukemic relapse and death. Given that NGS can simultaneously detect multiple leukemia‐associated mutations, it can be used in the majority of AML patients to monitor disease burdens and inform treatment decisions.

Background: Measurements of maternal fat mass (FM) are important for studies of maternal and fetal health. Common methods of estimating FM have not been previously compared in pregnancy with measurements using more complete body composition models. Objectives: The goal of this pilot study was to compare multiple methods that estimate FM, including 2-, 3-and 4-compartment models in pregnant women at term, and to determine how these measures compare with FM by dual-energy X-ray absorptiometry (DXA) 2 wk postpartum. Design: Forty-one healthy pregnant women with prepregnancy body mass index (in kg/m 2 ) 19 to 46 underwent skinfold thickness (SFT), bioelectrical impedance analysis (BIA), body density (D b ) via air displacement plethysmography (ADP), and deuterium dilution of total body water (TBW) with and without adjustments for gestational age using van Raaij (VRJ) equations at 37-38 wk of gestation and 2 wk postpartum to derive 8 estimates of maternal FM. Deming regression analysis and Bland-Altman plots were used to compare methods of FM assessment. Results: Systematic differences in FM estimates were found. Methods for FM estimates from lowest to highest were 4-compartment, DXA, TBW (VRJ) , 3-compartment, D b(VRJ) , BIA, air displacement plethysmography body density, and SFT ranging from a mean 6 SD of 29.5 6 13.2 kg via 4-compartment to 39.1 6 11.7 kg via SFT. Compared with postpartum DXA values, Deming regressions revealed no substantial departures from trend lines in maternal FM in late pregnancy for any of the methods. The 4-compartment method showed substantial negative (underestimating) constant bias, and the air displacement plethysmography body density and SFT methods showed positive (overestimating) constant bias. ADP via D b(VRJ) and 3-compartment methods had the highest precision; BIA had the lowest. Conclusions: ADP that uses gestational age-specific equations may provide a reasonable and practical measurement of maternal FM across a spectrum of body weights in late pregnancy. SFT would be acceptable for use in larger studies. This trial was registered at clinicaltrials.gov as NCT02586714.

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Serum proteomics analysis may lead to the discovery of novel osteoporosis biomarkers. The Osteoporotic Fractures in Men Study (MrOS) comprises men ≥65 in the US who have had repeated BMD measures and have been followed for incident fracture. High-throughput quantitative proteomic analysis was performed on baseline fasting serum samples from non-Hispanic white men using a multi-dimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). We followed the participants for a mean of 4.6 years for changes in femoral neck bone mineral density (BMD) and for incident hip fracture. Change in BMD was determined from mixed effects regression models taking age and weight into account. Participants were categorized into three groups: BMD maintenance (no decline; estimated change ≥ 0 g/cm2, n=453); expected loss (estimated change 0 to 1 SD below the estimated mean change, −0.034 g/cm2 for femoral neck, n=1184); and accelerated loss (estimated change ≥ 1 SD below mean change, n=237). Differential abundance values of 3,946 peptides were summarized by meta-analysis to determine differential abundance of each of 339 corresponding proteins for accelerated BMD loss vs maintenance. Using this meta-analytic standardized fold change at cutoffs of ≥ 1.1 or ≤ 0.9 (p < 0.10), 20 proteins were associated with accelerated BMD loss. Associations of those 20 proteins with incident hip fracture were tested using Cox proportional hazards models with age and BMI adjustment in 2473 men. Five proteins were associated with incident hip fracture (HR between 1.29 and 1.41 per SD increase in estimated protein abundance). Some proteins have been previously associated with fracture risk (e.g., CD14 and SHBG), while others have roles in cellular senescence and aging (B2MG and TIMP1) and complement activation and innate immunity (CO7, CO9, CFAD). These findings may inform development of biomarkers for future research in bone biology and fracture prediction.

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