Vulvovaginal graft-versus-host disease (GVHD) is an underdiagnosed and poorly recognized complication of hematopoietic stem cell transplantation (HSCT). Previous studies have reported findings restricted to predominantly adult populations. We report a case series of pediatric and young adult vulvovaginal GVHD, which was identified in 19 patients (median age, 11.8 years; range, 2.4 to 21.9 years) out of a total 302 female patients who underwent transplantation over an 8-year period at a pediatric HSCT center. The majority of patients had concomitant nongenital GVHD; only 1 patient had isolated vulvovaginal GVHD. The median time from bone marrow transplantation to diagnosis of vulvovaginal GVHD was 30 months (range, 2.3 to 97.5 months). A high percentage of the patients in our series were without vulvar or vaginal symptoms (n = 8; 42%), even though 17 patients (89%) presented with grade 3 disease based on current adult grading scales. Vulvar examination findings most frequently included interlabial and clitoral hood adhesions (89%), loss of architecture of the labia minora or clitoral hood (42%), and skin erosions or fissures (37%). Only 5 patients underwent a speculum exam, none of whom had vaginal GVHD. Examination findings of primary ovarian insufficiency (POI) can overlap with those of GVHD, and 6 patients (32%) in our cohort were diagnosed with POI. Only 1 patient was on systemic hormone replacement therapy at the time of vulvovaginal GVHD diagnosis. The majority of patients (n = 16) were treated with topical steroid therapy, with a median time to response of 43 days. Five patients (26%) had a complete response to therapy, and 10 patients (53%) had a partial response. This case series provides valuable insight into pediatric and young adult vulvovaginal GVHD and highlights the need for increased screening for vulvar disease in this population.

Summary-Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking.Background-Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery.Methods-Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of preatherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia.Results-Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51-75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51-75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening.Conclusions-In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. These observations indicate that in some settings, intimal hyperplasia may be part of the disease process of atherosclerosis, and that its formation may be influenced by traditional risk factors for atherosclerosis.

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Low levels of hydrogen peroxide (H(2)O(2)) are mitogenic to mammalian cells and stimulate the hyperphosphorylation of heterogeneous nuclear ribonucleoprotein C (hnRNP-C) by protein kinase CK1alpha. However, the mechanisms by which CK1alpha is regulated have been unclear. Here it is demonstrated that low levels of H(2)O(2) stimulate the rapid dephosphorylation of CK1alphaLS, a nuclear splice form of CK1alpha. Furthermore, it is demonstrated that either treatment of endothelial cells with H(2)O(2), or dephosphorylation of CK1alphaLS in vitro enhances the association of CK1alphaLS with hnRNP-C. In addition, dephosphorylation of CK1alphaLS in vitro enhances the kinase's ability to phosphorylate hnRNP-C. While CK1alpha appears to be present in all metazoans, analysis of CK1alpha genomic sequences from several species reveals that the alternatively spliced nuclear localizing L-insert is unique to vertebrates, as is the case for hnRNP-C. These observations indicate that CK1alphaLS and hnRNP-C represent conserved components of a vertebrate-specific H(2)O(2)-responsive nuclear signaling pathway.

INTRODUCTION: Rapid repeat pregnancy (within 2 years) among young women poses serious health consequences. Long-acting reversible contraception (LARC) is safe and effective, and available to women immediately postpartum at our institution. Our primary aim was to compare the rapid repeat pregnancy rate for young women (aged 13-24 years) initiating LARC immediately postpartum versus initiating LARC within 8 weeks of delivery, and LARC versus other contraceptive methods. METHODS: A retrospective cohort study was conducted of 592 young women with a live birth from 2011-2013 within our healthcare system. Logistic regression models were used to determine the odds of rapid repeat pregnancy. RESULTS: Women using short-acting or no contraception had higher adjusted odds of rapid repeat pregnancy compared to those using LARC (aOR 2.9, 95% CI 1.5-6.0; and OR 3.2, 95% CI 1.6-7.0). Immediate postpartum LARC initiation had higher odds of rapid repeat pregnancy versus LARC initiation within 8 weeks (aOR 2.2, 95% CI 1.0-5.0). The LARC removal/expulsion rate within 2 years was 46% with immediate postpartum placement and 36% with 8 week placement. Women receiving immediate postpartum LARC were more likely to be under 18 years old, had higher gravidity, and received primarily subdermal implants. CONCLUSION: Overall, postpartum LARC use among young women resulted in decreased risk of rapid repeat pregnancy compared to short-acting or no contraception. However, because of early LARC removal and switching to short-acting or no method, young women initiating LARC immediately postpartum were more likely to experience a rapid repeat pregnancy than those initiating LARC around 6-8 weeks postpartum.

Purpose of review The current article explores some of the more complex subtopics concerning adolescents and long-acting reversible contraceptives (LARC). Recent findings Recent research has highlighted ways in which LARC provision can be optimized in adolescents and has identified gaps in adolescent LARC access and utilization. Summary Contraceptive counseling for adolescents should be patient-centered, not necessarily LARC-first, to avoid coercion. There are increasing applications for the noncontraceptive benefits of LARC for several unique patient populations and medical conditions.

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