Influence of Sexually Transmitted Infections in Pregnant Adolescents on Preterm Birth and Chorioamnionitis.

Background: Adolescents have an increased risk of preterm birth (PTB) and sexually transmitted infections (STIs). We examined the prevalence and impact of STIs (gonorrhea, chlamydia, and trichomonas) on PTB and chorioamnionitis in pregnant adolescents. Methods: This retrospective cohort study utilized the first pregnancy delivered at an urban hospital among patients ≤ 19 years old over a 5-year period. Poisson regression with robust standard errors was used to estimate prevalence ratios (PR) and 95% confidence intervals (CI) of the association between STIs and PTB (<37 weeks) and chorioamnionitis identified by clinical or placental pathology criteria. Results: 739 deliveries were included. 18.8% (n = 139) of births were preterm. The overall prevalence of STIs during pregnancy was 16.5% (Chlamydia trachomatis: 13.1%, n = 97; Trichomonas vaginalis: 3.7%, n = 27; and Neisseria gonorrheae: 3.1%, n = 23). Detection of C. trachomatis, T. vaginalis, or N. gonorrheae was not associated with increased PTB. While infection with N. gonorrheae and C. trachomatis did not increase the likelihood of any chorioamnionitis, infection with T. vaginalis significantly increased the likelihood of any chorioamnionitis diagnosis (aPR 2.19, 95% CI 1.26-3.83). Conclusion: In this adolescent population with a high rate of PTB, in whom most received appropriate STI treatment, we did not find an association between STI during pregnancy and an increased rate of PTB. However, an infection with T. vaginalis was associated with an increased likelihood of chorioamnionitis. Early detection of STIs may prevent adverse pregnancy outcomes. Continued vigilance in STI screening during pregnancy, including consideration of universal Trichomonas vaginalis screening, is merited in this high-risk population.

Updates in SJS/TEN: collaboration, innovation, and community.

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

Stevens Johnson Syndrome: Past, Present, and Future Directions Gynecologic Manifestations and Management in SJS/TEN.

Stevens Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe mucocutaneous hypersensitivity disorders characterized by sudden onset epidermal necrosis. Acute manifestations of SJS/TEN often include vulvovaginal erosions, ulcerations, vaginal discharge, bleeding, vaginal pain, dysuria, and urinary retention. If not treated, this can lead to complications such as vulvovaginal adhesions, vaginal stenosis or dryness, pain, dyspareunia, bleeding, and adenosis. Even with adequate treatment, there are lasting impacts including difficulty with vaginal exams and psychological distress. Early recognition and treatment of vulvovaginal involvement are crucial to preventing severe sequelae. Despite the potentially devastating consequences of genitourinary involvement of SJS/TEN, involvement of the mucocutaneous surfaces of the vulva and vagina is inconsistently documented, and protocols for treatment and follow-up are not well-established. The treatment of vulvovaginal involvement relies largely on expert opinion, and there is little data on the efficacy of suggested management. The goal of this review was to identify whether establishing a clinical pathway increased treatment of vulvovaginal SJS/TEN and to optimize our standardized protocol to prevent genitourinary sequelae. Methods: We conducted a retrospective chart review of female patients with SJS/TEN at Harborview Medical Center, University of Washington from 2008 to 2021. Demographic and clinical data including gynecologic consultation, exam findings, treatment regimens, and outpatient follow-up were collected from the electronic medical record. We compared data before and after implementation of a clinical care pathway in 2017. Results: We reviewed a total of 88 charts of women with possible SJS/TEN between 2008 and 2021. Of these 88 charts, 77 were found to have clear biopsy proven diagnosis of SJS/TEN. A total of 42 patients were found to have vulvovaginal involvement (55%) and gynecology was consulted in 43% of cases. 50% of patients (n = 21) with vulvovaginal involvement were recommended treatment with vaginal dilators and steroid ointment and 34% of patients with genital involvement received no treatment.Between 2008 and May of 2017 (pre-protocol), we found 55 patients with SJS/TEN. 55% of patients (n = 29) had vulvovaginal involvement (n = 26 vulvar, n = 21 vaginal). Gynecology was only consulted in 26% (n = 14) of patients. Of the 21 females with vaginal involvement, only 38% (n = 8) had dilators/vaginal molds with steroid ointment recommended. Of the 26 females with vulvar involvement, 31% (n = 8) had no vulvar treatment recommendations with the remaining 69% having some documentation that ranged from gauze placement only (19%) to topical lidocaine, barrier cream, antibiotic or antifungal cream/ ointment, lubricant, or topical steroid ointment (50%). Menstrual suppression was recommended in 38% (n = 9) of menstruating females. An antifungal medication was only prescribed in 4% of patients.Following implementation of the clinical pathway for the treatment of SJS/TEN in 2017, 22 females with SJS/TEN were identified. 72% (n = 16) had documented vulvovaginal involvement (n = 16 vulvar, n = 9 vaginal). Gynecology consultations took place in 86% (n = 19) of patients. We identified several improvements after implementation of the protocol. Gynecology consults overall increased from 26% pre-, to 86% post-protocol. For patients with vulvovaginal involvement, consultations were completed in 93% compared to 50% prior to protocol. Of note, the finding of vulvovaginal lesions increased from 53 to 72%. Dilator use with topical steroid ointment was consistently recommended, as was antifungal use and menstrual suppression. Conclusion: Having a protocol in place for treatment of female patients with SJS/TEN increased the consistency of Gynecologic consultation and the documentation and treatment of vulvovaginal SJS/TEN. We identified the need to improve clinical follow-up after discharge from the hospital, which could be arranged as multidisciplinary visits and would be a good option to assess long-term outcomes (pain, sexual activity, etc.). With regards to future directions, we are in the process of assessing long-term data on quality of life and sexual functioning. The impact of treatment in the acute setting on the development of chronic sequelae needs to be established, as does the management of long-term sequelae like vaginal dryness, pain, dyspareunia. The role of local estrogen and vaginal laser still needs to be explored. Pelvic floor physical therapy might play a significant role in rehabilitation and has yet to be studied.

Imiquimod treatment of vulvar melanoma in situ invading the urethra.

The primary treatment of both in situ and invasive vulvar melanoma is wide local excision of the primary neoplasm. However, this can be a surgical challenge for size, multifocal presentation with proximity to urethra or anus and tendency for local recurrence. The data on adjuvant therapy for vulvar MIS is very limited. A 69-year-old patient with melanoma of the vulva underwent a simple vulvectomy with positive margins in peri-clitoral area, followed by modified radical vulvectomy and bilateral inguinofemoral sentinel lymph node dissection with negative margins. She was later diagnosed with MIS of the vulva on different locations and had multiple wide local excisions over several years. One lesion was close to the urethra and a complete excision was difficult. Topical imiquimod × 16 weeks (5% cream) was given. The regimen was augmented from 3 to 5 times weekly. Complete resolution was found at 16 weeks and patient was disease free for 4 years. Recently however, a vaginal melanoma was detected. Imiquimod appeared to be beneficial in the treatment of melanoma in situ of the vulva/ vagina when surgical options were not feasible producing local control of disease with the remaining risk for local and distant metastasis. Metastasis can appear years later, therefore long-term follow-up of patients treated with topical imiquimod is needed.

SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs.

Cardiac rotation and relaxation in patients with chronic heart failure.

BACKGROUND: The normal left ventricle shows a systolic wringing motion with clockwise rotation at the base and counterclockwise rotation at the apex. PURPOSE: The aim of the present study was (1) to assess left ventricular (LV) contraction and relaxation in patients with chronic heart failure (CHF), and (2) to evaluate the effect of medical therapy on LV contraction-relaxation behavior. METHODS: Magnetic resonance was used to examine LV motion by labeling specific LV regions in three planes (myocardial tagging). Twenty-three subjects were included, nine healthy controls and 14 CHF patients. Cardiac motion was determined from the deformation of a rectangular grid in a basal and apical plane. CHF patients were put on triple therapy with ACE-inhibitors, beta-blockers and spironolactone. Follow-up examination (n=9) was performed after 6 months. RESULTS: In controls, systolic rotation was -9.5+/-2 degrees at the base and +3.3+/-1 degrees at the apex. In CHF patients, rotation was reduced both at the base (-3.4+/-2 degrees , P<0.01) and the apex (+0.9+/-3 degrees , P<0.05). Similarly, regional ejection fraction (REF) was reduced in CHF patients both at the base and the apex. Medical therapy was associated with an improvement in REF, but systolic rotation improved only at the base (-4.6+/-2 degrees , P<0.05). CONCLUSIONS: Systolic wringing motion with clockwise rotation at the base and counterclockwise rotation at the apex is maintained in CHF although reduced. Heart failure treatment is associated with an improvement in REF, whereas rotation improved only at the base, but not at the apex. Thus, there is an uncoupling between regional shortening and rotation in CHF patients.

Two new loci, PLEIADE and HYADE, implicate organ-specific regulation of cytokinesis in Arabidopsis.

In screens for regulators of root morphogenesis in Arabidopsis we isolated six new recessive mutants with irregular cell expansion. Complementation analyses placed the mutations in two loci, PLEIADE (PLE) and HYADE (HYA). Phenotypic analyses revealed multinucleated cells, cell wall stubs, and synchronized cell divisions in incompletely separated cells that are all characteristics of defective cytokinesis. These defects were pronounced in roots and undetectable in aerial organs. In addition, fertility and germination were not affected by the mutations. Thus, the alleles that we have isolated of PLE and HYA suggest that the genes may encode organ-specific components needed primarily during root development. Analysis of microtubule arrays during cell cycle in ple and hya roots indicates that the presence of several synchronized nuclei influences the position of preprophase band, mitotic spindles, and phragmoplasts. The enhanced and synergistic phenotype of PLE/ple.hya/hya seedlings and double mutants point to a role of PLE and HYA in the same process. These mutants provide tools to elucidate the regulation of nuclear cytoskeletal interactions during cell division and cytokinesis.