Search Results (62)

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: Polycystic ovary syndrome (PCOS) is one of the most frequently diagnosed endocrine and metabolic disorders in women of reproductive age before menopause. It is associated with excess androgens and ovarian dysfunction, reduced fertility, the presence of obstetric disorders, but also metabolic disorders, and, among others, insulin resistance, obesity and type II diabetes. Its close relationship with changes in the diversity of the vaginal microbiome, vaginal inflammation and changes in the vaginal microenvironment, which can pave the way for pathogenic microorganisms, is emphasized. Methods: The research in the presented paper focuses on a group of women with PCOS (n = 490) of reproductive age (26–43 years), in whom the frequency of infections of the reproductive system caused by atypical pathogens, Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma spp., were analyzed, and then the immune system response was assessed in terms of the level of serum proinflammatory cytokines, IL-1β, IL-6 and TNF-α. Results: Our results showed a 40% infection rate in the studied group of patients with PCOS, with C. trachomatis being the most common pathogen (17.7%), followed by Ureaplasma spp. (10%) and M. hominis (4.9%). In some cases, co-infections such as Mycoplasma and Ureaplasma were also observed in 3.1% or all three atypical bacteria, M. hominis, Ureaplasma spp. and C. trachomatis, in 4.3% of patients with PCOS. In our study, in women with PCOS and confirmed infection with any atypical pathogen (n = 196), we analyzed the levels of proinflammatory cytokines, IL-1 β a, IL-6 and TNF-α. The results were compared with a control group (control group A) consisting of patients with the same underlying disease, i.e., PCOS (n = 39), who did not experience infection with atypical pathogens or symptoms of gynecological infection. Additionally, a control group B (n = 28) consisting of healthy women (without PCOS and without infection) was introduced. The results regarding the levels of cytokines studied in this work (IL-1β, IL-6, TNF-α) may suggest that the presence of intracellular C. trachomatis in the infection will play a dominant role in the immune system response. In the infections with atypical pathogens analyzed in this study in patients with PCOS, no characteristic clinical features were observed, apart from indications in the form of an increase in the number of leukocytes in the assessment of the vaginal biocenosis, suggesting cervicitis and reported reproductive failure or lower abdominal pain. An additional problem is the inability to detect the presence of atypical pathogens in routine microbiological tests; therefore, confirmation of such etiology requires referral of the patient for targeted tests. Conclusions: Invasion of host cells by atypical pathogens such as C. trachomatis and infections with “genital mycoplasmas” can disrupt the function of these cells and lead to many complications, including infertility. The immune response with the production of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6, observed in response to infection with C. trachomatis, M. hominis, and Ureaplasma spp., induces or amplifies inflammation by activating immune cells or controlling infection, but may lead to the facilitation of the survival of pathogenic microorganisms and irreversible damage to fallopian tube tissues. Especially in the case of the proinflammatory cytosine TNF-α, there seems to be a close correlation with infections with atypical pathogens and a marked immune response, as well as with increased IL-1β and IL-6 values compared with the absence of infection (both in the presence and absence of PCOS). The presented study may suggest the importance of extended diagnostics to include atypical pathogens in the case of PCOS and the importance of research in this area also from the point of view of the immune response. Full article

We report the case of a 5-year-old boy from a Sri Lankan migrant family in Catania, Italy, diagnosed with a Dirofilaria repens infection in the spermatic cord. The child presented with pain and swelling in the left inguinal area. Initial evaluation suggested orchiepididymitis, which was treated unsuccessfully with amoxicillin/clavulanate and NSAIDs. As symptoms worsened, torsion of the Morgagni hydatid was considered. An exploratory surgery revealed a firm mass in the left spermatic cord. Histopathological examination of the excised lesion showed fragments of a helminth within a granulomatous inflammatory reaction. Subsequent PCR analysis detected D. repens DNA. The patient fully recovered after surgical excision of the mass. Given the increasing incidence of human dirofilariasis, D. repens should be considered in the differential diagnosis of unexplained subcutaneous or inguinal nodules, especially in patients with a relevant travel history. This case highlights the importance of accurate diagnosis to avoid unnecessary invasive procedures or prolonged antimicrobial therapies. It represents one of the youngest pediatric cases with genital involvement reported in Italy, a country that accounts for half of the cases in Europe. Full article

Background and Clinical Significance: Implantation of an embryo in the cervical canal is the rarest location of ectopic pregnancy, as it occurs between 1 in 1000 and 1 in 18,000 pregnancies. Dilation and curettage in previous pregnancies have been identified as risk factors in most cases. Other predisposing factors include pelvic inflammatory disease (PID), prior tubal surgeries, assisted reproductive technologies, as well as the presence of fibroids and intrauterine. Importantly, ectopic pregnancies are the main cause of maternal morbidity and mortality in the first trimester. Given the rarity of cervical ectopic pregnancies (CEPs) and the lack of specific recommendations, clinical data supporting current evidence is of utmost significance. Case Presentation: A 29-year-old nulliparous woman presented with spotting from the genital tract and lower abdominal pain persisting for four days. Pregnancy could not be ruled out based on the patient’s medical history. The level of β-Human chorionic gonadotropin (β-HCG) on admission was 1487.99 mIU/mL. The first ultrasonography examination revealed a non-specific imaging appearance suggestive of the presence of cervical mucus. Targeted examination with visualization of the cervical canal revealed a gestational sac measuring 4–5 mm in diameter, containing an embryonic echo. The patient was treated with 84 mg of methotrexate (MTX) i.v. in a 1, 3, 5, 7 scheme along with 0.1 mg/kg calcium folinate i.m. in a 2, 4, 6, 8 scheme prior to curettage. Conclusions: A diagnosis of cervical pregnancy cannot be excluded even in the absence of prior risk factors. Methotrexate should be considered a safe and efficient option in the management of CEP. As shown in our case, early detection of CEP is of utmost significance. Full article

Background/Objectives: Chlamydia trachomatis (Ct) is the leading bacterial cause of sexually transmitted infection globally. If undiagnosed or left untreated, these infections can lead to serious complications such as infertility, ectopic pregnancies, and chronic pelvic pain. Despite the high prevalence and potential for serious health complications, no vaccine has been licensed. Pigs offer a valuable biomedical model for chlamydia research: they have an overall high degree of similarity to humans and serve as natural hosts for Chlamydia suis (Cs), a close relative of Ct. Thus, in this study, the pig model was used to evaluate a vaccine candidate against Ct. Methods: The vaccine candidate consists of chlamydial-protease-like activity factor (CPAF) protein adjuvanted with STING (Stimulator of Interferon Genes) pathway agonist cyclic-di-AMP (c-di-AMP). Pigs received two doses intramuscularly followed by two intranasal doses. Each week, the systemic T cell response was assessed via IFN-γ and IL-17 ELISpots, as well as multi-parameter flow cytometry on 0, 14, and 28 days post vaccination (dpv). The humoral immune response was analyzed by measuring CPAF-specific antibody levels and avidity via ELISAs. Results: Vaccination with c-di-AMP adjuvanted CPAF triggered low-level systemic IFN-γ and multifunctional IFN-γ⁺TNF-α⁺ CD4 T cell responses. Despite the rather low systemic effector cytokine production, robust anti-CPAF IgG responses were detected in serum, vaginal swab eluates, and oviduct flushes. Genital Ct challenge 42 dpv resulted in only transient infection, precluding a confident assessment of vaccine efficacy of the tested CPAF/c-di-AMP vaccine candidate. However, after challenge, vaccinated pigs exhibited boosted systemic anti-CPAF IFN-γ and mucosal IgG responses compared to unvaccinated pigs. Conclusions: Thus, while vaccine efficacy remains elusive, the CPAF/c-di-AMP vaccine candidate was immunogenic: it elicited a low-level systemic cell-mediated response and robust humoral immune responses. Future studies will incorporate a STING agonist directly conjugated to CPAF as well as addition of other Th1-inducing adjuvants to enhance cellular immunity. Full article

Background/Objectives: Migraine and endometriosis are two diseases that are associated with women. Endometriosis is a condition exclusively affecting the female population as it affects the female genital tract, while migraine is a primary headache disorder having the highest prevalence in women of reproductive age. Although, undoubtedly, they are two distinct disorders, some correlations have been suggested considering the epidemiological similarities. Methods: This systematic review aimed to analyze the putative links between those two diseases. Two databases were searched in accordance with the PRISMA guidelines, which led to the inclusion of 28 of the most appropriate studies. The review was registered in PROSPERO. Results: A comprehensive analysis of the existing literature allowed us to distinguish six different aspects: (i) the prevalence of migraine in the course of endometriosis, in general, (ii) when comparing endometriosis patients to healthy individuals, (iii) the relation between different migraine types and endometriosis, (iv) pain symptoms in patients with endometriosis and migraine, and finally, (v) molecular and (vi) genetic bases of the suspected correlation. Conclusions: Although not all results are definitely apparent, the results showed a higher prevalence of endometriosis and migraine together than both diseases separately. More precisely, chronic migraine was demonstrated to be the most possibly linked to endometriosis. Moreover, pain symptoms were usually more evident in patients suffering from both diseases at the time. Finally, some suggestions were presented due to this comorbidity’s molecular and genetic bases; however, the literature, especially on this topic, is lacking. Full article

Background/Objective: Actinomyces is a genus of anaerobic gram-positive bacteria. It forms part of human body microbiota commonly in the oral cavity and genital tract. During pregnancy, the organism may cause the rare chorioamnionitis, where the maternal genital tract or other sites such as the oral cavity will be the likely source of the pathogen. This condition may increase the risk of foetal morbidity and mortality, and preterm birth. Methods: The placenta of a 33-year-female, primigravida, who presented with preterm labour and eventual delivery of baby at 20 weeks gestation was sent for histopathological examination. Her antenatal and clinical history were reviewed, to identify possible aetiology for her preterm birth. Results: She is noted to have presented with sudden per-vaginal creamy coloured discharge with no associated odour and no irritation. The discharge became blood staining associated with labour pain, this followed by premature spontaneous rupture of membrane and pre-mature labour. Laboratory tests revealed leucocytosis, neutrophilia, monocytosis, high CRP and elevated derived fibrinogen. The patient was delivered of a live male baby weighing 0.35 kg, who died shortly after birth. Placenta microscopic examination revealed patchy severe acute chorioamnionitis and prominent clusters of Gram-positive filamentous bacteria with histopathologic features of Actinomyces spp. The mother before discharged was treated with oral antibiotic. Conclusions: The intrauterine Actinomyces spp. infection is associated with preterm birth and neonatal mortality, early diagnosis during ante-natal could perhaps prevent preterm birth and reduce the associated neonatal mortality. Full article

Background/Objectives: Regadenoson, a selective adenosine A_2A receptor agonist, is primarily prescribed for myocardial perfusion imaging (MPI). As its clinical use becomes more widespread in practice, assessing its safety in real-world settings is essential. Methods: In this research, disproportionality analysis was applied to evaluate the safety of Regadenoson by examining all adverse event (AE) reports since 2004 in the FDA Adverse Event Reporting System (FAERS), in which Regadenoson was identified as the primary suspected drug. The reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used to analyze AEs associated with Regadenoson. The Weibull distribution was utilized to model the temporal risk of AEs. Results: The results confirmed some known adverse reactions, such as nausea, shortness of breath (dyspnea), palpitations/vomiting, headache, dizziness, chest pain, and flushing (facial redness or warmth), which were also listed on the drug’s label. New potential adverse reactions not mentioned in the label were identified, including micturition urgency, mental status changes, conversion disorder, eye movement disorder, and genital paraesthesia. This study highlighted the significance of monitoring AEs, particularly right after the start of Regadenoson administration. Conclusions: This study provides preliminary safety data on Regadenoson’s real-world use, corroborating known adverse effects while uncovering new potential risks. These findings offer valuable safety insights for clinicians when prescribing Regadenoson for the use of MPI. Full article

Background/Objectives: Dienogest 0.5 mg tablets (DNG0.5) taken twice daily (1 mg/day) are more effective than cyclic low-dose estrogen/progestin/combined oral contraceptive (LEP/COC) in ameliorating dysmenorrhea pain and are recommended for dysmenorrhea treatment in Japan. However, their efficacy has not been directly compared with continuous LEP/COC regimens. Here, we evaluated the effectiveness of DNG0.5 compared to Yazflex^® (YZF), a continuous LEP, in treating dysmenorrhea. Methods: The efficacy of DNG0.5 in treating dysmenorrhea was compared retrospectively with that of Yazflex, the longest continuously administered LEP/COC available in Japan. Results: The improvement rates of dysmenorrhea scores at 3 and 6 months post-treatment were 59.1% and 66.4% in the LEP group (n = 113) and 88.1% and 96.4% in the DNG0.5 group (n = 125), respectively. The complete resolution rate of dysmenorrhea at 6 months was 88.0% in the DNG0.5 group and 23.9% in the LEP group. These findings indicate that DNG0.5 was significantly more effective than LEP (p < 0.01). DNG0.5 exerted an early pain-suppressing effect, which continued to increase thereafter. Furthermore, the presence of endometrial polyps, uterine fibroids, or adenomyosis, which are risk factors for irregular genital bleeding, was examined. Among these, endometrial polyps were particularly more likely to cause bleeding and potentially reduce the effect of DNG0.5; however, even with these three risk factors, DNG0.5 was more effective than LEP in reducing pain. Conclusions: Dienogest was more effective than LEP in managing dysmenorrhea, even at a dosage of 0.5 mg twice daily. However, factors affecting irregular vaginal bleeding should be considered when prescribing DNG0.5. Full article

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects about 1% of the world’s population. It is characterized by round, painful nodules, abscesses or sinuses, often in the genital area. HS has the worst impact on quality of life (QoL) of any dermatological condition. Methods: The aim of this systematic review is to analyze how HS affects patients’ sexual quality of life (SQoL), herein defined as a person’s evaluation of their sexual relationships, including physical and mental aspects, and their response to this evaluation. Results: The systematic search yielded 41 primary results. After screening, 6 studies were selected for this review. Men with HS suffer from lower SQoL than male controls and sexual dysfunction is more common in both male and female patients than in controls. Sexual dysfunction is worse in all HS patients than in controls, and worse in female patients than in male patients. Disease severity is not related to any of the sexual concepts analysed. Conclusions: HS has a strong impact on SQoL, as patients suffer from sexual dysfunction and sexual distress more often than healthy controls, and feel that their relationships are negatively affected by the disease. Therefore, the impact of HS on SQoL should be further investigated, especially the psychological aspect of SQoL. Full article

Many primary studies and reviews have been published on the influence of chronic diseases (CDs) on sexual dysfunction (SD), but CDs not involving the genitals are less well represented in the literature. Aim: To determine the prevalence of SD in patients with non-genital CD and assess the overall impact on sexual functioning. Methods: An umbrella review was performed of published systematic reviews on the relationship between the occurrence of CDs not involving the genitals and patients’ sexual functioning, following the PRISMA guidelines. PubMed, EMBASE, the Cochrane Library, PsycInfo, Scopus, and CINAHL were used to find publications for inclusion in the review, with two independent researchers performing the search and selection of articles, data extraction, and quality assessment. The relative risk (RR) or odds ratio (OR) with 95% confidence was used as an indicator of the association between CD and SD across studies. The quality of studies included in the review was assessed using Amstar-2. Outcomes: Forty-three systematic reviews, thirty of which included a meta-analysis, met the inclusion criteria, representing a total of 880,586 patients (756,629 (85.9%) men, 68,388 (7.8%) women, and 55,569 (6.3%) unspecified). Results: Among men, CD is associated with erectile dysfunction, and among females, with lower levels of desire, arousal, lubrication, orgasm, and sexual satisfaction and with increased pain during intercourse. For both men and women, depression, anxiety, and fatigue are also reported, while women with CD are more affected by a poor body image than men. Clinical implications: Patients with CD, especially females, should be more routinely assessed for the impact of their condition on sexual functioning. The impact of CD on men’s sexuality has been extensively studied in terms of erectile capacity, but other aspects of their sexuality are largely neglected. Strengths and limitations: This is the first umbrella review to bring together the documented findings regarding sexual dysfunction among patients with various non-genital CDs. While the heterogeneity of the CDs makes the study unique and clinically relevant, it renders the interpretation of the results more difficult. The overrepresentation of men in existing studies reflects the current state of research but limits the applicability of the findings for women. Conclusions: Women and men with non-genital CDs can suffer from SD or reduced sexual function. Health professionals should pay more attention to managing these sexual disorders, even when the disease does not affect the genitals. 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

Background. Perineoplasty is a frequently performed procedure as part of prolapse surgery. Despite its frequent use, there is a lack of evidence on the optimal indication, surgical technique and adverse outcomes. We intended to gain insight into the current opinions on indications and techniques of perineoplasty among (uro)gynecologists worldwide. Methods. We conducted a survey among members of the International UroGynecological Association (IUGA) to objectify indications for perineoplasty and aspects of surgical technique. Results. A total of 114 urogynecologists responded, with 98% performing perineoplasty. A total of 85% of respondents aimed to approximate the bulbocavernosus muscle, whereas 27% aimed to include the puborectal muscle as well. A total of 86% of respondents used 1–4 resorbable sutures, especially vicryl 2/0 (39%) or vicryl 0 (52%). According to the respondents, a “wide genital hiatus at physical examination” (87%) and “subjective complaints of a wide genital hiatus” (84%) were considered good/excellent indications for perineoplasty, whereas “fecal incontinence”, “apical prolapse” and “perineal pain” were absolutely/mostly not a good indication. Reasons to not perform perineoplasty were pelvic pain (59%) and dyspareunia (64%). Most responders underlined the need for more research on this topic (8.5 out of 10). Conclusions. Perineoplasty is a frequently performed procedure. There is a wide variation in the indications for and surgical techniques of perineoplasty. Therefore, research is needed to identify which patients will benefit from perineoplasty and how to optimally perform this surgery. Full article

Sexual shame negatively affects women’s sexual functioning, impacting arousal, desire, orgasm, and pain. This review summarizes the existing literature, highlighting the multiple, interacting factors contributing to sexual shame including sociocultural messages, body and genital self-image, sexual self-schemas, sexual pain, comorbid chronic disease, illness, medical disorders, and sexual trauma. The relationship between sexual shame and sexual functioning is often reciprocal, demonstrating sexual shame as a potential causal and maintaining mechanism underlying women’s sexual difficulties. We present a model proposing the mechanisms by which sexual shame affects sexual functioning, underscoring the need for comprehensive approaches to mitigate the impact of sexual shame and foster sexual well-being for women. Growing research emphasizes emotional processes in models of sexual function, and emotional pathways underlying sexual difficulties and dysfunction. Given the impact of sexual shame on women’s sexual functioning, therapeutic approaches that target sexual shame are recommended to help alleviate difficulties with sexual arousal, desire, orgasm, and sexual pain. Full article

Genital herpes simplex virus (HSV) is associated with a reduction in quality of life and adverse outcomes. The aim of this study is to assess the interest and expectations for a therapeutic HSV vaccine among individuals diagnosed with genital herpes in Italy. A retrospective survey was conducted at the Infectious Diseases Unit of the IRCCS San Raffaele Scientific Institute, Milan, Italy. The study collected data on demographics, clinical history and interest in HSV vaccination. The results showed that 87.5% of participants were interested in a therapeutic vaccine, with interest higher among younger people and those with frequent genital herpes recurrences. Participants most expected the vaccine to reduce the pain associated with outbreaks, followed by a reduction in the frequency and duration of recurrences. These findings underscore the strong demand for a therapeutic HSV vaccine, especially among those who experience recurrent outbreaks, and highlight the importance of considering patient expectations when developing preventive and therapeutic strategies for genital herpes. Full article