Search Results (71)

Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article

Background/Objectives: Endocrine disruptors (EDs) are xenobiotic chemicals that disrupt hormone signaling and homeostasis within the human body. Accumulative evidence proposes that EDs could affect systemic hormone balance and local microbial communities, including the female genital tract (FGT) microbiome. The FGT microbiome, and especially the vaginal microbiota, contributes significantly to reproductive health maintenance, defense against infection, and favorable pregnancy outcomes. Disruption of the delicate microbial environment is associated with conditions like bacterial vaginosis, infertility, and preterm birth. Methods: The present narrative review summarizes the existing literature on EDs’ potential for changing the FGT microbiome. We discuss EDs like bisphenol A (BPA), phthalates, and parabens and their potential for disrupting the FGT microbiome through ED-induced hormone perturbations, immune modulation, and epithelial barrier breach, which could lead to microbial dysbiosis. Results: Preliminary evidence suggests that ED exposure–microbial composition changes relationships; however, robust human evidence for EDs’ changes on the FGT microbiome remains scarce. Conclusions: Our review addresses major research gaps and suggests future directions for investigation, such as the necessity for longitudinal and mechanistic studies that combine microbiome, exposome, and endocrine parameters. The relationship between EDs and the FGT microbiome could be critical for enhancing women’s reproductive health and for steering regulatory policies on exposure to environmental chemicals. Full article

Pelvic organ prolapse (POP) is a common pelvic floor disorder with substantial impact on women’s quality of life, necessitating accurate and reproducible diagnostic methods. This study investigates the use of three-dimensional (3D) transperineal ultrasound, integrated with artificial intelligence (AI), to evaluate pelvic floor biomechanics and identify correlations between biometric parameters and prolapse severity. Thirty-seven female patients diagnosed with genital prolapse (mean age: 65.3 ± 10.6 years; mean BMI: 29.5 ± 3.8) were enrolled. All participants underwent standardized 3D transperineal ultrasound using the Mindray Smart Pelvic system, an AI-assisted imaging platform. Key biometric parameters—anteroposterior diameter, laterolateral diameter, and genital hiatus area—were measured under three functional states: rest, maximal Valsalva maneuver, and voluntary pelvic floor contraction. Additionally, two functional indices were derived: the distensibility index (ratio of Valsalva to rest) and the contractility index (ratio of contraction to rest), reflecting pelvic floor elasticity and muscular function, respectively. Statistical analysis included descriptive statistics and univariate correlation analysis using Pelvic Organ Prolapse Quantification (POP-Q) system scores. Results revealed a significant correlation between laterolateral diameter and prolapse severity across multiple compartments and functional states. In apical prolapse, the laterolateral diameter measured at rest and during both Valsalva and contraction showed positive correlations with POP-Q point C, indicating increasing transverse pelvic dimensions with more advanced prolapse (e.g., r = 0.42 to 0.58; p < 0.05). In anterior compartment prolapse, the same parameter measured during Valsalva and contraction correlated significantly with POP-Q point AA (e.g., r = 0.45 to 0.61; p < 0.05). Anteroposterior diameters and genital hiatus area were also analyzed but showed weaker or inconsistent correlations. AI integration facilitated real-time image segmentation and automated measurement, reducing operator dependency and increasing reproducibility. These findings highlight the laterolateral diameter as a strong, reproducible anatomical marker for POP severity, particularly when assessed dynamically. The combined use of AI-enhanced imaging and functional indices provides a novel, standardized, and objective approach for assessing pelvic floor dysfunction. This methodology supports more accurate diagnosis, individualized management planning, and long-term monitoring of pelvic floor disorders. Full article

Pelvic floor fistulas are abnormal communications between the lower urinary tract and/or anorectum and the female genital tract. Classification systems for female pelvic floor fistulas have existed for over 150 years. At present, there is no consensus on a classification system. Traditionally, classification systems were used for obstetric fistulas. Earlier classification systems were descriptive (small/large/simple/complex) to communicate clinical findings. More recently, classification systems, in particular the Goh and Waaldijk systems, have been tested to predict the outcome of surgical closure and the risk of post-fistula closure urinary incontinence. Conclusions: Features of the fistula may predict outcomes following fistula surgery but other patient features and surgical experience and skill also play a role in the results. Full article

Background/Objectives: We generated a novel recombinant Vibrio cholerae ghost (rVCG)-based subunit vaccine incorporating the A1 subunit of cholera toxin (CTA1) and a multiepitope Chlamydia trachomatis (CT) antigen (MECA) derived from five chlamydial outer membrane proteins (rVCG-MECA). The ability of this vaccine to protect against a CT transcervical challenge was evaluated. Methods: Female C57BL/6J mice were immunized thrice at two-week intervals with rVCG-MECA or rVCG-gD2 (antigen control) via the intramuscular (IM) or intranasal (IN) route. PBS-immunized mice or mice immunized with live CT served as negative and positive controls, respectively. Results: Vaccine delivery stimulated robust humoral and cell-mediated immune effectors, characterized by local mucosal and systemic CT-specific IgG, IgG2c, and IgA antibody and IFN-γ (Th1 cytokine) responses. The elicited mucosal and systemic IgG2c and IgA antibody responses persisted for 16 weeks post-immunization. Immunization with rVCG-MECA afforded protection comparable to that provided by IN immunization with live CT EBs without any side effects, irrespective of route of vaccine delivery. Conclusions: The results underline the potential of a multiepitope vaccine as a promising resource for protecting against CT genital infection and the potential of CTA1 on the VCG platform as a mucosal and systemic adjuvant for developing CT vaccines. Full article

Hypothyroidism causes ovarian dysfunction and infertility in women and animals and impairs the hypothalamic expression of kisspeptin (Kp). However, kisspeptin is also expressed in the genital system, and the lack of the Kp receptor (Kiss1r) in the uterus is linked to reduced implantation rates. This study investigated the impact of hypothyroidism on the uterine expression of Kp and Kiss1r in female rats throughout the estrous cycle and the associated changes in uterine activity modulators. Hypothyroidism was induced through daily administration of propylthiouracil (PTU) over a period of 14 days. Plasma levels of LH, E₂, and P₄, cyclicity, body and uterine weight, uterine histomorphometry, and the gene and/or protein expression of Kiss1, Kiss1r, estrogen receptor α (ERα), progesterone receptor (PR), and thyroid hormone receptor α (TRα) were assessed. Additionally, proliferative activity (CDC-47) and the gene expression of uterine receptivity mediators (SMO, WNT4, BMP2, HAND2, MUC1, and LIF) were evaluated. Hypothyroidism prolonged the diestrus and increased progesterone levels during this phase, while decreasing luteinizing hormone and estradiol on proestrus. In the uterus, hypothyroidism reduced Kp immunostaining on diestrus and KISS1R mRNA levels on proestrus. These changes were accompanied by reduced endometrial glands, reduced uterine proliferative activity, and reduced ERα gene and protein expression. Additionally, hypothyroidism led to reduced uterine gene expression of LIF, BMP2, WNT4, and HAND2. On the other hand, thyroid hypofunction increased uterine PR and TRα immunostaining, while it reduced PGR gene expression on diestrus. These findings demonstrate that hypothyroidism reduces the expression of Kiss1/Kiss1r system in the uterus, which is associated with disrupted uterine estrogen and progesterone signaling and reduced expression of uterine receptivity mediators across the rat estrous cycle. Full article

Sandflies, small insects primarily from the Psychodidae family, are commonly found in sandy, tropical, and subtropical regions. Most active during dawn and dusk, female sandflies feed on blood to facilitate egg production. In doing so, they can transmit infectious diseases that may cause symptoms such as fever, headaches, muscle pain, anemia, skin rashes, and ulcers. Importantly, sandflies are species-specific in their disease transmission. Determining the gender and species of sandflies typically involves examining their morphology and internal anatomy using established identification keys. However, this process requires expert knowledge and is labor-intensive, time-consuming, and prone to misidentification. In this paper, we develop a highly accurate and efficient convolutional network model that utilizes pharyngeal and genital images of sandfly samples to classify the sex and species of three sandfly species (i.e., Phlebotomus sergenti, Ph. alexandri, and Ph. papatasi). A detailed evaluation of the model’s structure and classification performance was conducted using multiple metrics. The results demonstrate an excellent sex-species classification accuracy exceeding 95%. Hence, it is possible to develop automated artificial intelligence-based systems that serve the entomology community at large and specialized professionals. Full article

The prevalence of female reproductive system disorders is increasing, especially among women of reproductive age, significantly impacting their quality of life and overall health. Managing these diseases effectively is challenging due to the complex nature of the female reproductive system, characterized by dynamic physiological environments and intricate anatomical structures. Innovative drug delivery approaches are necessary to facilitate the precise regulation and manipulation of biological tissues. Nanotechnology is increasingly considered to manage reproductive system disorders, for example, nanomaterial imaging allows for early detection and enhances diagnostic precision to determine disease severity and progression. Additionally, nano drug delivery systems are gaining attention for their ability to target the reproductive system successfully, thereby increasing therapeutic efficacy and decreasing side effects. This comprehensive review outlines the anatomy of the female upper genital tract by highlighting the complex mucosal barriers and their impact on systemic and local drug delivery. Advances in nano drug delivery are described for their sustainable therapeutic action and increased biocompatibility to highlight the potential of nano drug delivery strategies in managing female upper genital tract disorders. Full article

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease. Full article

Background: Lichen sclerosus (LS) is a chronic, inflammatory dermatosis that affects both genital and extragenital sites. It is often difficult to treat and may lead to a variety of complications if not adequately treated. The mainstay of therapy involves topical corticosteroids, topical calcineurin inhibitors, and systemic immunomodulators. Although a variety of topical, oral, and procedural therapies are available, a review comparing relative efficacy is lacking. To this end, this systematic review aimed to summarize the literature regarding treatment modalities and their respective response rates in patients with genital LS. Methods: A literature search was conducted in accordance with PRISMA guidelines. Results: This review qualitatively summarizes information from 31 randomized controlled trials, encapsulating a total of 1507 patients with LS, the majority of which were female (n = 1374, 91%). Topical corticosteroids, the mainstay of therapy for LS, were discussed throughout the literature, and proved to be more efficient than topical calcineurin inhibitors, topical hormonal therapy, topical vitamin E oil and cold cream. However, other treatment modalities proved to be more efficient than topical corticosteroids, including CO₂ and Nd:YAG laser therapies, and the addition of polydeoxyribonucleotide intradermal injections, to steroid therapy. Finally, other modalities that proved to be efficient in the treatment of LS included silk undergarments, human fibroblast lysate cream, platelet-rich plasma, acitretin, and surgical intervention. The risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials. Limitations included the inclusion of only randomized controlled trials, moderate or high risk of bias, and heterogeneity in treatment regimens, among others. Conclusion: Although high-potency topical corticosteroids have validated efficacy in the management of LS, other treatment modalities, including steroid-sparing agents and/or procedural adjuncts, have been demonstrated to have a beneficial role in the treatment of LS. Full article

Background: Vulvovaginal atrophy (VVA) significantly impacts the quality of life in breast cancer patients leading to symptoms like vaginal dryness, dyspareunia, and genital discomfort. Quality of life in this context is measured using validated scales like the Vaginal Health Index, Visual Analog Scale (VAS), and the Female Sexual Function Index (FSFI). Methods: We performed a systematic review and meta-analysis to identify effective treatment options for VVA, including topical estrogen, systemic hormone therapy, vaginal DHEA, ospemifene, and non-hormonal methods like intravaginal laser therapy, moisturizers, and lubricants. A systematic search of four databases (MEDLINE, Scopus, CENTRAL, Embase) identified studies on VVA treatment efficacy in breast cancer patients, yielding 13,039 records, with 32 eligible studies and 8 included in the meta-analysis. Results: Significant improvements were found with intravaginal laser therapy, showing notable differences in the Vaginal Health Index (MD = 8.24, p < 0.01), dyspareunia (MD = −4.82, p = 0.05), and dryness (MD = −5.05, p = 0.01). However, no significant changes were observed in FSFI and vaginal pH. Notably only intravaginal laser therapy was included in the meta-analysis, as other treatment options lacked comparable data. Both hormonal and non-hormonal treatments improved quality of life, with laser therapy showing the most substantial effects. Conclusions: Intravaginal laser therapy is an effective treatment for VVA symptoms in breast cancer survivors, particularly in improving the Vaginal Health Index and reducing dyspareunia. Despite the strengths of the study, variability among studies, lack of RCT-s and data limitations, especially on long-term effects, present challenges. Full article

The Phytoseiulus persimilis specialized in preying on Tetranychus species, with particularly strong predation capability against Tetranychus urticae. To investigate the morphology of female reproductive structures and effects of different gravid times on structures of oocytes and embryos in Phytoseiulus persimilis, we employed paraffin sectioning, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) on the model species of predatory mite Phytoseiulus persimilis. The female adult possessed several reproductive organs, including paired solenostomes, major ducts, embolus, calyces, and vesicles within the sperm-access system, as well as lyrate organ and the ovary. Furthermore, the reproductive system also encompassed the uterus, vagina, and genital pore, which were involved in egg development and expulsion. The solenostomes were situated between the third and fourth legs, and they were scarcely discernible in virgin, but they became apparent during mating. The occurrence of mating significantly influenced the nucleus of lyrate organ. In virgin, the nucleus exhibited underdeveloped morphology, whereas in mated individuals, it was well-formed. However, the duration of mating did not impact its development. The cellular structure of the ovary was solely associated with the stage of the surrounding oocyte and was not directly linked to mating occurrences. The uterus was barely visible outside of mating periods but became observable 12 h after mating when eggs were present within the body. At this point, it opened in preparation for egg laying when both the vagina and reproductive opening were open. Positioned in front of the vesicle but behind the ovary was the lyrate organ, with its lower part housing the uterus. The vagina was connected to the genital pore. No significant difference was observed in oocyte morphology between the virgin ovaries and the mated. Oocyte development occurred through four stages: during stage I (4–9 h after mating), yolk accumulation took place; stage II (10 h after mating) involved egg relocation; stage III (12–13 h after mating) was marked by eggshell formation; finally, at stage IV (14–16 h after mating), embryonic development commenced, leading to egg deposition. The fusion of sperm and egg occurred approximately 9–10 h after mating. These findings established a solid foundation for investigating the Phytoseiid reproductive mechanisms. Full article

Recently, studies suggest that the protective effects of Lactobacillus within the female reproductive tract may be partly due to their ability to form biofilms. This study aims to explore the possibility that Lactobacillus can produce key mediators to further bolster the survival of biofilms in human vaginal microbiomes. Three bacterial species, namely, Lactobacillus gasseri, L. crispatus, and L. jensenii, sourced from human female subjects were used to carry out experiments examining the growth of biofilms using a microfermenter system. The bacteria were used to inoculate a glass rod spatula which was subsequently transferred to the microfermenter system. The resulting biofilm growing on the glass spatula was harvested in media and stored in a −80 °C freezer for gas chromatography–mass spectroscopy analysis. We found that quorum sensing compounds, acyl homoserine lactones (AHLs), were detected in the biofilm of L. crispatus and L. jensenii, but none were detected in L. gasseri. The biofilm produced by L. crispatus and L. jensenii was much higher in quantity than the biofilm produced by L. gasseri. Aside from oligopeptides quorum sensing, lactobacilli were found to also have AHL compounds that may help them produce more biofilms and improve the survival and growth of their bacterial communities in the female genital area. Full article

Complex urogenital malformations are clinically highly relevant; thus, they must be appropriately diagnosed and classified before initiating treatment. Background/Objectives: This study aimed to evaluate the applicability and suitability of the embryological–clinical classification of female genital malformations. Methods: A systematic review of cases of genital malformations reported in the literature from 2000 to 2020 was conducted. Case reports and series with the following combinations: “female genital tract” AND (malformation OR anomaly OR müllerian anomaly OR uterine anomaly OR cervical anomaly OR vaginal anomaly OR cloacal anomaly OR urogenital sinus); and “female genital tract” AND (renal agenesis OR ectopic ureter) were searched. A total of 3124 articles were identified, of which 824 cases of genital malformation were extracted. The characteristics of each malformation were included in a database for further analyses. Results: Using the embryological–clinical classification, 89.9% of the published cases and 86.5% of the 52 cases defined as unclassifiable by their authors have been classified in this review. In 73 cases (72.2%), the classification of the malformation using the AFS system was incomplete because although the type of uterine anomaly of the AFS classification matched that of the embryological–clinical classification, characteristics of the urinary system or the vagina were overlooked when using the AFS system. Following a dispersion matrix, we have been able to show that the embryological–clinical classification system is able to classify and subclassify the genitourinary malformations more accurately. Conclusions: The applicability of the embryological–clinical classification has been confirmed after classifying most of the cases of genital malformation previously published. This system also provides a more complete and accurate classification than other classifying systems exclusively based on Müllerian duct development or uterovaginal parameters, demonstrating its suitability. Full article

Schistosomiasis is a neglected parasitic disease linked to water, posing a global public health concern with a significant burden in sub-Saharan Africa. It is transmitted by Schistosoma spp., causing both acute and chronic effects affecting the urogenital or the hepato-intestinal system. Through granuloma formation, chronic schistosomiasis weakens host immunity, heightening susceptibility to coinfections. Notably, female genital schistosomiasis (FGS), a disregarded gynecological condition, adversely affects girls’ and women’s reproductive health and increases vulnerability to HIV. This review explores the intricate interplay between schistosomiasis and HIV, considering their geographical overlap. We delve into the clinical features of this coinfection, underlying mutual influences on transmission, diagnostic challenges, and therapeutic approaches. Understanding the dynamics of FGS and HIV coinfection is pivotal for integrated healthcare strategies in regions with co-endemicity, aiming to mitigate the impact of the two infections on vulnerable populations. Full article