Haematopoietic innate interleukin 17A production drives immunopathology in female mouse genital Chlamydia muridarum infection.

Chlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A-/- mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A-/- immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)-/- female mice and observed a significant reduction in immunopathology in IL17RA-/- mice. WT bone marrow transplants to IL17RA-/- recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early C. muridarum infection of the female reproductive tract.

An Update on Prenatal Diethylstilbestrol Exposure and High-Grade Squamous Intraepithelial Lesions of the Lower Genital Tract.

Women with prenatal diethylstilbestrol exposure are excluded from less frequent cervical cancer screening because of their increased neoplasia risk. We report the results of a prospective follow-up study of prenatal diethylstilbestrol exposure and lower genital tract high-grade (grade 2 or higher) squamous intraepithelial lesions (HSIL). The age-adjusted risk of HSIL among diethylstilbestrol-exposed women (n=4,062) was higher than among the diethylstilbestrol unexposed (n=1,837) through age 44 years (hazard ratio 2.03, 95% CI, 1.31-3.14) but not age 45 years or older. Elevated HSIL risk remained higher in diethylstilbestrol-exposed women, after accounting for frequency of cervical cancer screening. Compared with unexposed women, HSIL risk was higher among women with earlier gestational and high-dose diethylstilbestrol exposure. These data confirm the appropriateness of more frequent screening among diethylstilbestrol-exposed women through age 44 years. Whether those aged 45 years or older should continue to have increased screening will require careful weighing of possible risks and benefits.

Geriatric Genital Dermatology.

As women age, hormonal changes set the stage for a variety of vulvovaginal pathologies. Health care providers in long-term care facilities should be able to recognize and treat these conditions, especially because residents may be unable to communicate their discomfort. The objective of this article is to highlight the major vulvovaginal conditions affecting older women and provide up-to-date information on treatment for providers in long-term care facilities.

Dermoscopy of oral and genital mucosal lesions: A descriptive cross-sectional study protocol.

INTRODUCTION: Dermoscopy is a safe, rapid, and non-invasive tool that aids in the clinical examination of pigmented and non-pigmented lesions. The upward trend in the use of dermoscopy can be attributed to the availability of compact hand-held and sophisticated dermoscopes, that are small enough to be carried around in a pocket. The extent of dermoscopy is not only limited to the evaluation of cutaneous lesions but also involves its use in the assessment of mucosal lesions along with lesions of hair and nails. METHODS: In a descriptive cross-sectional study, subjects (n = 100) with oral or genital mucosal lesions will be enrolled. Following a thorough clinical examination, a dermoscopy of the lesion will be performed with Dermlite DL4© Dermoscope, having a magnification of 10x. Images obtained would be stored and evaluated for observing specific morphologic patterns on dermoscopy which would be utilized to describe those patterns and arrive at a specific diagnosis. Descriptive statistics will include mean and standard deviation to summarise quantitative variation. Dermoscopic features of oral and genital mucosal lesions will be estimated in percentage. PURPOSE OF STUDY: Mucosal lesions several times mimic each other morphologically. Performing a biopsy is not always feasible for oral and genital lesions because they may be difficult to reach and tend to bleed more profusely compared to the skin surface due to its rich vascular nature. Dermoscopy is a non-invasive tool that helps in the diagnosis that is used mostly for the evaluation of non-mucosal lesions. For the same reason, there is no or minimal information in the published literature with regard to dermoscopic patterns of mucosal lesions. The current study intends to describe dermoscopic patterns in oral and genital mucosal diseases so that this important information would assist the diagnosis in a non-invasive manner thereby reducing the need for invasive investigations like mucosal biopsy. EXPECTED CLINICAL OUTCOMES: To summarize, this research is intended to add to the scarce literature on dermoscopic findings of oral and genital mucosal lesions. The study findings would establish the diagnosis and eliminate the need for unwarranted invasive biopsies of mucosal lesions and, if need be, help in the selection of the biopsy site.

Verruciform Xanthoma: Clinical and Morphologic Spectrum Across Oral, Genital, and Cutaneous Sites.

BACKGROUND: Verruciform xanthoma (VX) is an uncommon, benign epithelial lesion of the oral mucosa. While this entity can also present extraorally, including on the skin and in anogenital areas, the variation in its histologic features in extraoral sites is not yet well defined. Differences in the demographics and morphologic features of oral versus extraoral VX were assessed to help facilitate the accurate diagnosis and management of this lesion. METHODS: After obtaining IRB approval, 110 cases of diagnosed VX were retrospectively collected from our institutional archives spanning from 2000 to 2022. Patient age, gender, available medical history, lesion appearance, and duration were obtained for each case. RESULTS: The median age was 55 years (range 13-86) with a male-to-female ratio of 1.2:1. The most common oral sites, in descending order, were the palate (n = 24, 22%), buccal mucosa (n = 18, 16%), gingiva (n = 16, 15%), and tongue (n = 13, 12%). Extraoral sites comprised 9% of all lesions, including the scrotum (9), vulva (2), cheek (1), wrist (1), gluteal region (1), and abdominal wall (1). The median size for all lesions was 6.0 mm, and extraoral lesions were associated with a 6.7 mm larger size compared to oral lesions (B ± SE: 6.7 ± 2.5 cm, p = 0.01). The lesions were most frequently pink or white in color and often described as papillary, pedunculated, verrucous, and/or exophytic. Microscopically, the presence of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated inflammation significantly differed between oral and extraoral lesions. Prominent wedge-shaped parakeratosis (p = 0.04) and keratin projections above the epithelium/epidermis (p < 0.001) were more prevalent in extraoral lesions. There was no significant link between keratin projections and epithelial atypia (p = 0.44). CONCLUSIONS: Familiarity with the broad morphological spectrum of VX, including the presence and degree of wedge-shaped parakeratosis, keratin projections above the epithelium/epidermis, and associated underlying inflammation, will be helpful in diagnosing it in unusual locations.

New concept in urologic surgery: The total extended genital sparing radical cystectomy in women.

INTRODUCTION AND OBJECTIVES: The aim of the study was to evaluate genital sparing radical cystectomy surgery in female patients from the point of view of both oncologic and functional outcomes (with emphasis on urinary and sexual outcomes) in a single high-volume center for the treatment of muscular invasive bladder cancer. MATERIALS AND METHODS: Between January 2014 and January 2018, 14 female patients underwent radical cystectomy with preservation of genital organs (the entire vagina, uterus, fallopian tubes, ovaries) and orthotopic urinary neobladder (Padua neobladder). Inclusion criteria were recurrent T1G3 tumors; refractory tumors after BCG therapy without associated carcinoma in situ (CIS); T2 or T3a tumors entirely resected at endoscopic transurethral resection of the bladder and not involving urethra/bladder trigone. Exclusion criteria were: T3b or higher bladder cancer, associated CIS and involvement of urethra or bladder trigone. Oncological and histopathological outcomes (Overall Survival - OS, Recurrence Free Survival - RFS), urinary outcomes (day and night incontinence, intermittent catheterization use, Sandvik Score) and sexual outcomes (Female Sexual Function Index 19 FSFI-19) were considered. The average follow-up time was 56 months. RESULTS: Considering oncological outcomes, histologic examination reported urothelial carcinoma in 13/14 patients; 8/13 patients (61.5%) had high grade T1 stage, 3/13 patients (23%) had high grade T2 stage and finally 2/13 patients (15.5%) had high-grade T3 stage. One patient presented with embryonal rhabdomyosarcoma completely excised after surgery (PT2aN0M0). No patient developed local or metastatic recurrence (RFS 100%); OS was 100%. Considering urinary continence outcomes, 12/14 patients retained daytime and nighttime continence (85.5%); 2/14 (14.5%) complained of low stress urinary incontinence daily and nighttime urinary leakage. The Sandvik Score showed complete continence in 7/14 patients (50%); mild degree incontinence in 6/14 patients without use of incontinence devices (43%); moderate degree of incontinence in one patient (7%). The FSFI administered at 1 year from the surgery showed sexual desire in all patients (100%); subjective arousal, achievement of orgasm and sexual satisfaction in 12/14 patients (85.5%); sufficient lubrication in 11/14 patients (78.5%). Only one patient (7%) complained about dyspareunia during sexual intercourse. CONCLUSIONS: Our study aims to demonstrate that genital-sparing radical cystectomy is a safe surgery in terms of oncologic outcomes and, most importantly, that it is beneficial in terms of urinary and sexual function. Indeed, patients' quality of life together with their psychological and emotional health should be put on the same level as oncological safety. However, it is a treatment reserved for selected patients who are strongly motivated to preserve fertility and sexual function and thoroughly informed about the benefits and complications of such a procedure.

Ovotesticular Difference of Sex Development: Genetic Background, Histological Features, and Clinical Management.

BACKGROUND: Ovotesticular disorder/difference of sex development (DSD) refers to the co-presence of testicular and ovarian tissue in one individual. Childhood management is challenging as there are many uncertainties regarding etiology, gonadal function, and gender outcome. SUMMARY: Ovotesticular DSD should mainly be considered in 46,XX children with atypical genitalia and normal adrenal steroid profiles. Various underlying genetic mechanisms have been described. Histological assessment of ovotestes requires expert revision and has many pitfalls. Neonatal sex assignment is essential, but as gender outcome is unpredictable, this should be regarded as provisional until a stable gender identity has developed. Therefore, it is crucial not to perform any irreversible medical or surgical procedure in affected individuals until adolescents can give their full informed consent. Gonadal function mostly allows for spontaneous pubertal development; however, fertility is compromised, especially in boys. Specific long-term outcome data for ovotesticular DSD are lacking but can be extrapolated from studies in other DSD populations. KEY MESSAGES: Management of ovotesticular DSD has changed in recent years, prioritizing the child's future right for autonomy and self-determination. The benefits and pitfalls of this new approach have not been documented yet and require intensive monitoring on an international scale.

Association of childhood vaccination with pediatric lichen planus: A systematic review.

Lichen planus (LP) is a chronic T-cell-mediated mucocutaneous inflammatory disease, largely recognized in adults. It is uncommon in children, and the literature present still lacks comprehensive understanding mainly due to underreporting of such cases. LP shows atypical clinical features, when seen in children, mainly affecting the flexor aspect of the wrists, legs, and the oral and genital mucosae. It is largely considered an autoimmune response of the body with various etiologic factors. Its association with vaccination is still an interesting field for research. The focus of the present systematic review was to discover the link of vaccine in the pathogenesis of juvenile LP. An electronic search was carried out using MEDLINE by PubMed, Google Scholar, and Web of Science databases. Articles that reported LP in children with prior records for vaccination were selected for the present systematic review. Twenty-three published articles in the English language were included for the quantitative and qualitative syntheses. The demographic data, specific vaccine history, and clinical details of the lesions were recorded. The existing evidence supports that vaccines could play an important role in etiopathogenesis of pediatric LP.

Oncological and functional outcomes of female reproductive organ-sparing radical cystectomy and ileal neobladder construction.

OBJECTIVES: To examine the oncological and urinary functional outcomes of reproductive organ-sparing radical cystectomy (ROS-RC) and U-shaped ileal neobladder construction in females compared with male patients. METHODS: We retrospectively examined 357 patients (281 male and 76 female) with muscle-invasive bladder cancer who were treated with RC plus U-shaped ileal neobladder construction between May 1996 and July 2021. All female patients were treated with ROS-RC. We compared disease-free survival (DFS), cancer-specific survival (CSS), overall survival (OS), and urinary functional outcomes between male and female patients. We evaluated the effect of gender on DFS, CSS, and OS. Furthermore, urinary functional outcomes were evaluated in 140 males and 48 females using a pressure-flow study at 3, 6, 9, and 12 months postoperatively. RESULTS: Female patients were considerably older than male patients at the time of radical cystectomy. No significant difference was noted in the tumor stage preoperatively. The multivariable Cox regression analysis with an inverse probability treatment weighted model revealed that the female gender was not significantly related to DFS, CSS, and OS. Moreover, urinary functions at 12 months were not markedly different between males and females, except for the capacity of the neobladder, detrusor pressure, and maximum urethral closure pressure. CONCLUSIONS: This study demonstrates that female patients with ROS-RC and U-shaped ileal neobladder construction did not significantly correlate with worse oncological outcomes. The combination of ROS-RC and U-shaped ileal neobladder construction might attain adequate urinary function without sacrificing oncologic outcomes.

CT features of malignant tubular genital tract tumors in seven goats.

Neoplasia of the tubular genital tract in goats, while rarely described, is most commonly reported as uterine adenocarcinoma, leiomyoma, or leiomyosarcoma. In this retrospective, single-center, case series, medical records were searched for goats with a computed tomography (CT) diagnosis of tubular genital mass and a definitive histologic (surgical biopsy or necropsy) diagnosis of malignant neoplasia. Data recorded from CT images were presence of peritoneal/retroperitoneal fluid, urinary tract obstruction, abdominal lymphadenomegaly, additional abdominal nodules/masses, and pulmonary nodules. For masses, maximum cross-sectional area, contrast enhancement, and uterine luminal fluid accumulation were also recorded. Seven goats met the inclusion criteria (leiomyosarcoma n = 5, adenocarcinoma n = 2). Both goats with adenocarcinoma had upper urinary tract obstruction, moderate to severe regional lymphadenopathy, peritoneal fluid, and peritoneal or hepatic nodules/masses; one goat with adenocarcinoma was discharged and subsequently euthanized, and the other had palliative mass debulking and was lost to follow up. Goats with leiomyosarcoma had infrequent, mild peritoneal fluid and mild sublumbar lymphadenopathy. Of the goats with leiomyosarcoma, two were euthanized at or near the time of CT imaging, two were euthanized at the time of surgery due to perceived mass non-resectability, and one had mass regression approximately four months post ovariohysterectomy but was subsequently lost to follow up. Five goats had pulmonary nodules, three of which had pathologic confirmation (pulmonary metastasis in a single patient with adenocarcinoma, and lungworm granulomas in two goats with leiomyosarcoma). Severe sublumbar lymphadenopathy and obstructive uropathy were sequelae in the two caprine patients with genital adenocarcinoma, and in none with leiomyosarcoma.

Superior antiviral activity of IFNß in genital HSV-1 infection.

Type I interferons (IFNs) present the first line of defense against viral infections, providing antiviral, immunomodulatory and antiproliferative effects. The type I IFN family contains 12 IFNα subtypes and IFNß, and although they share the same receptor, they are classified as non-redundant, capable to induce a variety of different IFN-stimulated genes. However, the biological impact of individual subtypes remains controversial. Recent data propose a subtype-specificity of type I IFNs revealing unique effector functions for different viruses and thus expanding the implications for IFNα-based antiviral immunotherapies. Despite extensive research, drug-resistant infections with herpes simplex virus type 1 (HSV-1), which is the common agent of recurrent orogenital lesions, are still lacking a protective or curing therapeutic. However, due to the risk of generalized infections in immunocompromised hosts as well as the increasing incidence of resistance to conventional antiherpetic agents, HSV infections raise major health concerns. Based on their pleiotropic effector functions, the application of type I IFNs represents a promising approach to inhibit HSV-1 replication, to improve host immunity and to further elucidate their qualitative differences. Here, selective IFNα subtypes and IFNß were evaluated for their therapeutic potential in genital HSV-1 infections. Respective in vivo studies in mice revealed subtype-specific differences in the reduction of local viral loads. IFNß had the strongest antiviral efficacy against genital HSV-1 infection in mice, whereas IFNα1, IFNα4, and IFNα11 had no impact on viral loads. Based on flow cytometric analyses of underlying immune responses at local and peripheral sites, these differences could be further assigned to specific modulations of the antiviral immunity early during HSV-1 infection. IFNß led to enhanced systemic cytokine secretion and elevated cytotoxic responses, which negatively correlated with viral loads in the vaginal tract. These data provide further insights into the diversity of type I IFN effector functions and their impact on the immunological control of HSV-1 infections.

Left pleural effusion in a young woman with genital tuberculosis.

Disseminated tuberculosis is a rare form of tuberculosis that can cause severe illness if diagnosed and treated late. We present the case of a young Senegalese woman who had a miscarriage due to a pelvic inflammatory disease, followed by the development of a left pleural effusion. Despite laparoscopic findings and a salpinx biopsy that revealed necrotizing granulomas, only microbiological examinations of pleural biopsies revealed the final diagnosis of disseminated, drug-sensitive tuberculosis.

Chlamydia transmitting from the genital to gastrointestinal tract and inducing tubal disease: Double attack pattern. / ç”Ÿæ®–é“è¡£åŽŸä½“ä¼ æ’­è‡³èƒƒè‚ é“å¹¶é¶å‘è¯±å¯¼è¾“åµç®¡ç— å˜­­åŒé‡æ”»å‡»æ¨¡å¼.

Chlamydia trachomatis ( CT ) genital tract infection is insidious, and patients often have no conscious symptoms.Delayed treatment after infection can lead to serious complications. Chlamydia muridarum ( CM ) genital tract infection in female mice can simulate CT genital tract infection in women, which is an ideal model to investigate the pathogenesis of CT . CM plasmid protein pGP3, chromosomal protein TC0237/TC0668, CM -specific CD8 + T cells, TNF-α, and IL-13 can induce genital tract inflammation, CD4 + T cells are responsible for CM clearance. However, tubal inflammation persists after genital tract CM is removed. Genital tract CM can spread spontaneously in vivo and colonize the gastrointestinal (GI) tract, but the GI tract CM cannot reverse spread to the genital tract. The survival time and number of CM transmitted from genital tract to GI tract are positively correlated with the long-term lesion of oviduct, while the CM inoculated directly into the GI tract has no pathogenicity in both the genital and GI tract. The double attack pattern of Chlamydia -induced genital tract inflammatory lesions is as follows: CM infection of oviduct epithelial cells initiates the process of oviduct repair as the first attack. After genital CM spreads to the GI tract, activated chlamydia-specific CD8 + T cells are recruited to the genital tract and secreted pro-fibrotic cytokines such as TNF-α and IL-13. This process is called the second attack which transform tubal repair initiated by the first attack into long-term tubal fibrosis/hydrosalpinx. Elucidating the pathogenic mechanism of Chlamydia infection can provide new ideas for the development of Chlamydia vaccine, which is expected to solve the problems of infertility caused by repeated CT infection in women.

[Pediatric genital lichen sclerosus: a case series of 11 girls].

BACKGROUND: Genital lichen sclerosus decreases the quality of life of women; 10-15% of cases occur in prepubertal girls. METHODS: Retrospective and descriptive study on the characteristics of girls diagnosed with genital lichen sclerosus at the Hospital Universitario de Navarra (Pamplona, Spain) between 2019 and 2022. RESULTS: Eleven girls aged between 4 and 14 year-old were diagnosed. Frequently, diagnostic delays were up to two years after the appearance of the lesions; the girl with a four-year delay showed a significant vulvar architectural alteration. All cases showed the typical sclerotic lesions on the genital area, and two of them also on the back. While six patients were asymptomatic, the rest reported pruritus and/or pain. Treatment with high/very high potency topical cortico-steroids achieved a good partial response, without complete remission of the lesions. CONCLUSION: Early diagnosis of genital lichen sclerosus is key to start early treatment, avoiding ireversible genital structural alteration.

Evaluation of a microperforate hymen leading to the incidental diagnosis of a borderline ovarian tumour.

Microperforate hymens are rare anatomical variants with an unknown incidence and very few reported cases. Borderline ovarian tumours are similarly uncommon, with an incidence of approximately 0.002%-0.006%. The concurrent presence of a microperforate hymen and a borderline ovarian tumour is therefore exceedingly unique with no documented cases to date. In this report, we review the case of a nulliparous woman in her late 20s who initially presented with an inability to have penetrative intercourse. A subocclusive hymenal variant was noted on examination and further imaging work-up resulted in the incidental discovery of a large ovarian mass subsequently noted to be a borderline ovarian tumour. Herein, we review contemporary approaches to the diagnosis and management of both hymenal variants and borderline ovarian tumours, and discuss fertility-sparing strategies for young women diagnosed with ovarian neoplasms.