Impact of helminth infections during pregnancy on maternal and newborn Vitamin D and on birth outcomes.

Poor birth outcomes in low- and middle income countries are associated with maternal vitamin D deficiency and chronic helminth infections. Here, we investigated whether maternal Schistosoma haematobium affects maternal or cord vitamin D status as well as birth outcomes. In a prospective cross-sectional study of pregnant women conducted in Lambaréné, Gabon, we diagnosed maternal parasitic infections in blood, urine and stool. At delivery we measured vitamin D in maternal and cord blood. S. haematobium, soil-transmitted helminths, and microfilariae were found at prevalences of 30.2%, 13.0%, and 8.8%, respectively. Insufficient vitamin D and calcium levels were found in 28% and 15% of mothers, and in 11.5% and 1.5% of newborns. Mothers with adequate vitamin D had lower risk of low birthweight babies (aOR = 0.11, 95% CI 0.02-0.52, p = 0.01), whilst offspring of primipars had low cord vitamin D levels, and low vitamin D levels increased the risk of maternal inflammation. Maternal filariasis was associated with low calcium levels, but other helminth infections affected neither vitamin D nor calcium levels in either mothers or newborns. Healthy birth outcomes require maintenance of adequate vitamin D and calcium levels. Chronic maternal helminth infections do not disrupt those levels in a semi-rural setting in sub-Saharan Africa.

Detection of hidden antibiotic resistance through real-time genomics.

Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the accuracy of genomics-based resistance predictions persist, particularly when compared to traditional, clinically established diagnostic methods. Here, we leverage the case of a multi-drug resistant Klebsiella pneumoniae infection to demonstrate how real-time genomics can enhance the accuracy of antibiotic resistance profiling in complex infection scenarios. Our results show that unlike established diagnostics, nanopore sequencing data analysis can accurately detect low-abundance plasmid-mediated resistance, which often remains undetected by conventional methods. This capability has direct implications for clinical practice, where such "hidden" resistance profiles can critically influence treatment decisions. Consequently, the rapid, in situ application of real-time genomics holds significant promise for improving clinical decision-making and patient outcomes.

How Old Is Too Old? Outcomes of Prolapse Native-Tissue Repair through Uterosacral Suspension in Octogenarians.

INTRODUCTION: Medical advancements are expected to lead to a substantial increase in the population of women aged 80 and older by 2050. Consequently, a significant number of individuals undergoing corrective prolapse surgery will fall into the elderly-patient category. The research indicates a notable rise in complications associated with prolapse surgery in patients older than 80, irrespective of frailty and other risk factors. Despite these challenges, the vaginal approach has been identified as the safest surgical method for pelvic organ prolapse (POP) repair in the elderly population. For this reason, we aimed to investigate the efficacy, complication rate, and functional outcomes associated with vaginal hysterectomy and an apical suspension/high uterosacral ligaments suspension as a primary technique for prolapse repair, both within a cohort of elderly patients. METHODS: We retrospectively analyzed patients who underwent transvaginal hysterectomy plus an apical suspension procedure for stage ≥ II and symptomatic genital prolapse between January 2006 and December 2013. Anatomical and functional outcomes were evaluated. The Patient Global Impression of Improvement (PGI-I) score was used to evaluate subjective satisfaction after surgery. RESULTS: Sixty-five patients were included in the analysis. The median age was 81.3 years. All individuals exhibited an anterior compartment prolapse stage II or higher, and the majority also a central prolapse stage II or higher. Notably, all participants reported symptoms of vaginal bulging. Over half of the population (58.6%) complained of incomplete bladder emptying. The intervention for all participants involved a vaginal hysterectomy with an apical suspension. Sixty-three patients (96.9%) and forty-four patients (67.6%) underwent a simultaneous anterior or posterior repair, respectively. Long-term complications (>30 days from surgery) were observed during follow-up, with a median duration of 23 ± 20 months. Seven (10.7%) anatomical recurrences were recorded, five (7.69%) concerning the anterior compartment, one (1.5%) the central, and three (4.6%) the posterior. Nevertheless, none of them necessitated further surgical intervention due to symptoms. Significant anatomical improvements for the anterior, central, and posterior compartments were noticed, compared to preoperative assessment (p < 0.001 for Aa and Ba, p < 0.001 for Ap and Bp, and p < 0.001 for C). PGI-I values established that 100% of patients were satisfied (PGI-I ≥ 2), with a median score of 1.12. Consequently, objective and subjective cure rates were 89.5% and 100%, respectively. CONCLUSION: Vaginal hysterectomy combined with apical suspension, particularly high uterosacral ligaments suspension, is a safe and effective primary surgical approach, even in elderly patients.

A Novel Method for the Measurement of the Vaginal Wall Thickness by Transvaginal Ultrasound: A Study of Inter- and Intra-Observer Reliability.

Background and Objectives: A consensus regarding the optimal sonographic technique for measuring vaginal wall thickness (VWT) is still absent in the literature. This study aims to validate a new method for measuring VWT using a biplanar transvaginal ultrasound probe and assess both its intra-operator and inter-operator reproducibility. Material and Methods: This prospective study included patients with genitourinary syndrome of menopause-related symptoms. Women were scanned using a BK Medical Flex Focus 400 with the 65 × 5.5 mm linear longitudinal transducer of an endovaginal biplanar probe (BK Medical probe 8848, BK Ultrasound, Peabody, MA, USA). Vaginal wall thickness (VWT) measurements were acquired from the anterior and posterior vaginal wall at three levels. Results: An inter-observer analysis revealed good consistency between operators at every anatomical site, and the intra-class coefficient ranged from 0.931 to 0.987, indicating high reliability. An intra-observer analysis demonstrated robust consistency in vaginal wall thickness measurements, with an intra-class coefficient exceeding 0.9 for all anatomical sites. Conclusions: The measurement of vaginal wall thickness performed by transvaginal biplanar ultrasound was easy and demonstrated good intra- and inter-operator reliability.

Changes in Pelvic Floor Ultrasonographic Features after Flat Magnetic Stimulation in Women with Chronic Pelvic Pain and Levator Ani Muscle Hypertonicity.

Background and Objectives: Chronic pelvic pain (CPP) represents a major public health problem for women with a significant impact on their quality of life. In many cases of CPP, due to gynecological causes-such as endometriosis and vulvodynia-improper pelvic floor muscle relaxation can be identified. Treatment of CPP with pelvic floor hypertonicity (PFH) usually involves a multimodal approach. Traditional magnetic stimulation has been proposed as medical technology to manage muscle hypertonicity and pelvic pain conditions through nerve stimulation, neuromodulation, and muscle relaxation. New Flat Magnetic Stimulation (FMS)-which involves homogeneous rather than curved electromagnetic fields-has the potential to induce sacral S2-S4 roots neuromodulation, muscle decontraction, and blood circulation improvement. However, the benefits of this new technology on chronic pelvic pain symptoms and biometrical muscular parameters are poorly known. In this study, we want to evaluate the modification of the sonographic aspect of the levator ani muscle before and after treatment with Flat Magnetic Stimulation in women with chronic pelvic pain and levator ani hypertonicity, along with symptoms evolution. Materials and Methods: A prospective observational study was carried out in a tertiary-level Urogynaecology department and included women with CPP and PFH. Approval from the local Ethics Committee was obtained before the start of the study (protocol code: MAGCHAIR). At the baseline, the intensity of pelvic pain was measured using a 10 cm visual analog scale (VAS), and patients were asked to evaluate their pelvic floor symptoms severity by answering the question, "How much do your pelvic floor symptoms bother you?" on a 5-answer Likert scale. Transperineal ultrasound (TPU) was performed to assess anorectal angle (ARA) and levator ani muscle minimal plane distance (LAMD). Treatment involved Flat Magnetic Stimulation alone or with concomitant local or systemic pharmacological therapy, depending on the patient's preferences. FMS was delivered with the DR ARNOLD system (DEKA M.E.L.A. Calenzano, Italy). After the treatment, patients were asked again to score the intensity of pelvic pain using the 10 cm visual analog scale (VAS) and to evaluate the severity of their pelvic floor symptoms on the 5-answer Likert scale. Patients underwent TPU to assess anorectal angle (ARA) and levator ani muscle minimal plane distance (LAMD). Results: In total, 11 patients completed baseline evaluation, treatment, and postoperative evaluation in the period of interest. All patients underwent eight sessions of Flat Magnetic Stimulation according to the protocol. Adjuvant pharmacological treatment was used in five (45.5%) patients. Specifically, we observed a significant increase in both ARA and LAMD comparing baseline and post-treatment measurements (p < 0.001). Quality of life scale scores at baseline and after treatment demonstrated a significant improvement in both tools (p < 0.0001). Conclusions: Flat Magnetic Stimulation, with or without adjuvant pharmacological treatment, demonstrated safety and efficacy in reducing pelvic floor hypertonicity, resulting in improvement in symptoms' severity and sonographic parameters of muscular spasm.

Viral genome sequencing to decipher in-hospital SARS-CoV-2 transmission events.

The SARS-CoV-2 pandemic has highlighted the need to better define in-hospital transmissions, a need that extends to all other common infectious diseases encountered in clinical settings. To evaluate how whole viral genome sequencing can contribute to deciphering nosocomial SARS-CoV-2 transmission 926 SARS-CoV-2 viral genomes from 622 staff members and patients were collected between February 2020 and January 2021 at a university hospital in Munich, Germany, and analysed along with the place of work, duration of hospital stay, and ward transfers. Bioinformatically defined transmission clusters inferred from viral genome sequencing were compared to those inferred from interview-based contact tracing. An additional dataset collected at the same time at another university hospital in the same city was used to account for multiple independent introductions. Clustering analysis of 619 viral genomes generated 19 clusters ranging from 3 to 31 individuals. Sequencing-based transmission clusters showed little overlap with those based on contact tracing data. The viral genomes were significantly more closely related to each other than comparable genomes collected simultaneously at other hospitals in the same city (n = 829), suggesting nosocomial transmission. Longitudinal sampling from individual patients suggested possible cross-infection events during the hospital stay in 19.2% of individuals (14 of 73 individuals). Clustering analysis of SARS-CoV-2 whole genome sequences can reveal cryptic transmission events missed by classical, interview-based contact tracing, helping to decipher in-hospital transmissions. These results, in line with other studies, advocate for viral genome sequencing as a pathogen transmission surveillance tool in hospitals.

High Uterosacral Ligaments Suspension for Post-Hysterectomy Vaginal Vault Prolapse Repair.

Background and Objectives: Uterosacral ligaments (USLs) suspension is a well-studied, safe, and long-lasting technique for central compartment correction. Preliminary clinical experiences showed encouraging data for this technique, also for post-hysterectomy vaginal vault prolapse surgical treatment. However, up-to-date evidence for post-hysterectomy vaginal vault prolapse repair through high uterosacral ligaments suspension is limited. Consequently, with this study, we aimed to assess the efficiency, complications frequency, and functional results of native-tissue repair through USLs in vaginal vault prolapse. Materials and Methods: This was a retrospective study. Women with symptomatic vaginal vault prolapse (≥stage 2) who underwent surgery with transvaginal native-tissue repair by high uterosacral ligaments were included. Patient characteristics, preoperative assessment, operative data, postoperative follow-up visits, and re-interventions were collected from the hospital's record files. High uterosacral ligament suspension was performed according to the technique previously described by Shull. A transverse apical colpotomy at the level of the post-hysterectomy scar was performed in order to enter the peritoneal cavity. USLs were identified and transfixed from ventral to dorsal with three absorbable sutures. Sutures were then passed through the vaginal apex and tightened to close the transverse colpotomy and suspend the vaginal cuff. At the end of the surgical time, a diagnostic cystoscopy was performed in order to evaluate ureteral bilateral patency. Using the POP-Q classification system, we considered an objective recurrence as the descensus of at least one compartment ≥ II stage, or the need for a subsequent surgery for POP. The complaint of bulging symptoms was considered the item to define a subjective recurrence. We employed PGI-I scores to assess patients' satisfaction. Results: Forty-seven consecutive patients corresponding to the given period were analyzed. No intraoperative complications were observed. We observed one postoperative hematoma that required surgical evacuation. Thirty-three patients completed a minimum of one-year follow-up (mean follow-up 21.7 ± 14.6 months). Objective cure rate was observed in 25 patients (75.8%). No patients required reintervention. The most frequent site of recurrence was the anterior compartment (21.2%), while apical compartment prolapse relapsed only in 6% of patients. An improvement in all POP-Q parameters was recorded except TVL which resulted in a mean 0.5 cm shorter. Subjective recurrence was referred by 4 (12.1%) patients. The mean satisfaction assessed by PGI-I score was 1.6 ± 0.8. Conclusion: This analysis demonstrated that native-tissue repair through high USL suspension is an effective and safe procedure for the treatment of post-hysterectomy vaginal vault prolapse. Objective, subjective, functional, and quality of life outcomes were satisfactory, with minimal complications.

Impact of Mannitol Bladder Distension in the Intraoperative Detection of Ureteral Kinking During Pelvic Floor Surgery.

INTRODUCTION AND HYPOTHESIS: Ureteral injuries are the most feared complications of gynecological surgery and therefore intraoperative recognition is of the utmost importance. Intraoperative cystoscopy represents the diagnostics of choice to investigate ureteral patency thanks to the direct visualization of ureteral flows after administration of infusion mediums. In this study, we aimed to compare the diagnostic performance of saline versus mannitol intraoperative cystoscopy in terms of false negatives in a large cohort of patients. METHODS: We retrospectively analyzed data of patients who underwent vaginal hysterectomy and high uterosacral ligament suspension for POP. Patients were divided in two groups based on the use of saline or mannitol medium for intraoperative cystoscopy. Postoperative daily control of serum creatinine was performed until discharge, as well as urinary tract imaging, in symptomatic patients. RESULTS: A total of 925 patients underwent vaginal hysterectomy followed by high USL suspension for POP. Saline and mannitol medium were used in 545 patients and 380 patients respectively. Postoperative ureteral injuries were identified in 12 patients, specifically in 2% of the saline group and in 0.3% of the mannitol group. CONCLUSIONS: The use of mannitol instead of saline as a bladder distension medium was able to significantly reduce the occurrence of postoperative ureteral sequelae.

Epidemiology of intestinal helminthiasis with an emphasis on taeniasis in Chipata district of the Eastern province of Zambia.

BACKGROUND: Intestinal helminth infections are among the most common infections worldwide and have a negative impact on the health, education, nutrition and economic development of affected populations. This study aimed to estimate the prevalence of intestinal helminthiasis, including T. solium taeniasis, using a large-scale community-based study in Chiparamba area of Chipata District in the Eastern province of Zambia. METHODS/PRINCIPAL FINDINGS: A cross-sectional study was conducted between June 2019 and December 2022 in a rural community of 25 randomly selected villages known to be at risk for T. solium infection. Stool samples were examined for intestinal helminths using the formol-ether concentration technique and further tested for taeniasis by copro antigen-ELISA (copro Ag-ELISA). Descriptive statistical analyses were conducted, and associations between the disease prevalence of active infections and individual- and village-level variables were determined using the chi-square or Fisher's exact test. Predictors of an individual being positive for either taeniasis or other soil-transmitted helminths were determined using binary logistic regression. A total of 2762 stool samples were examined. One hundred ninety-five (7.1%) tested positive for at least one helminthic parasite on microscopy, with hookworm being the most frequent 84 (3.0%), followed by S. mansoni, 66 (2.4%). For taeniasis, 11 (0.4%) participants were positive for Taenia spp. microscopically, while 241 (8.7%) tested positive via copro Ag-ELISA. On bivariate analysis, male sex was significantly associated with the prevalence of intestinal parasites (p = 0.012) but not with that of taeniasis based on copro Ag-ELISA results. Village level differences were significant for infection with intestinal helminths as well as for taeniasis positivity on copro Ag-ELISA (p <0.001). CONCLUSION: Intestinal helminths, including T. solium taeniasis, are prevalent in Chiparamba area of Chipata district in the eastern province of Zambia, supporting the clear need for further targeted public health interventions for surveillance and control.

Flat Magnetic Stimulation for Urge Urinary Incontinence.

Background and Objectives: Strategies for overactive bladder syndrome (OAB) management involve, among others, strengthening the bladder outlet to suppress urgency and neuromodulating the sacral roots. Magnetic stimulation (MS) is a technology that involves an extracorporeal device that is able to provide an electromagnetic field specifically designed to interact with pelvic floor neuromuscular tissue. The resulting tissue electrical activity induces contraction of the pelvic muscle and neuromodulation of the S2-S4 sacral roots. Flat Magnetic Stimulation (FMS) is a relevant advancement involving homogeneous electromagnetic fields, which are able to optimize the effect on the entire pelvic area. However, the benefits of this new technology for OAB syndrome are poorly known. Consequently, the aim of our study is to analyze the outcomes and quality of life (QoL) impact of FMS with Dr. Arnold (DEKA, Calenzano, Italy) in women suffering from OAB syndrome associated with urinary incontinence. Materials and Methods: This prospective study included patients with OAB, urge urinary incontinence, and no ongoing OAB treatments. At baseline (T0), the Incontinence Impact Questionnaire (IIQ-7), the Female Sexual Function Index (FSFI-19), and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) were collected. Patients underwent 8 FMS sessions of 25 min each in one month. At the termination of the therapy (T1), women repeated the ICIQ-UI SF, FSFI-19, and IIQ-7 tools. Moreover, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected to evaluate the cure rate. Results: Our study enrolled a total of 57 consecutive patients. Most women had at least one second- or third-line treatment before FMS, while the remaining naive patients had contraindications to pharmacological treatments. No women reported adverse effects during the treatment. After the treatment, we observed a decrease in the IIQ-7 (p < 0.001) and ICIQ-UI SF scores (p < 0.001) and an improvement in sexual function (p < 0.001) evaluated with FSFI-19. According to PGI-I scores, 42 (73.7%) women referred to some kind of improvement, scoring ≤ 3 points. Specifically, 8.7% of patients considered themselves very much improved, 29.8% much improved, 35.1% minimally improved, and 26.3% found no changes. FMS was effective in treating OAB symptoms without any adverse effects. The mechanism is supposed to be related to suppressing the initiation of micturition. This makes FMS a promising device for treating naive and refractory urge urinary incontinence. Conclusions: The new FMS represents a promising non-pharmacological option for the treatment of naive and refractory OAB.

Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions.

Interleukins are secreted proteins that regulate immune responses. Among these, the interleukin 12 (IL-12) family holds a central position in inflammatory and infectious diseases. Each family member consists of an α and a ß subunit that together form a composite cytokine. Within the IL-12 family, IL-35 remains particularly ill-characterized on a molecular level despite its key role in autoimmune diseases and cancer. Here we show that both IL-35 subunits, IL-12α and EBI3, mutually promote their secretion from cells but are not necessarily secreted as a heterodimer. Our data demonstrate that IL-12α and EBI3 are stable proteins in isolation that act as anti-inflammatory molecules. Both reduce secretion of proinflammatory cytokines and induce the development of regulatory T cells. Together, our study reveals IL-12α and EBI3, the subunits of IL-35, to be functionally active anti-inflammatory immune molecules on their own. This extends our understanding of the human cytokine repertoire as a basis for immunotherapeutic approaches.

Efficacy of a Diode Vaginal Laser in the Treatment of the Genitourinary Syndrome of Menopause.

INTRODUCTION: Genitourinary syndrome of menopause (GSM) and vulvovaginal atrophy (VVA) are the most frequent menopause-related clinical entities and are consistently included in the definition of pelvic floor disorders (PFDs). Nonhormonal therapies, such as lubricants and moisturizers, are indicated as first-line treatments, while the "gold standard'' is represented by topical estrogen products; however, in cancer survivors hormonal treatment is not indicated. For this reason, energy-based therapeutic approaches-for instance, through laser technologies-may be employed as alternative options in this kind of patient; however, there are no studies evaluating the efficacy of a pure diode vaginal laser in the treatment of GSM. As a consequence, with our study, we aimed to evaluate outpatient nonablative diode laser treatment in sexually active women, with contraindications, no response, or refusal of local estrogenic therapy. METHODS: This prospective study included patients with GSM, aged ≥ 18 years old, with contraindications, or refusal of local estrogen therapies. Women were evaluated via the use of their Vaginal Health Index (VHI) scores, which consists of five measures: elasticity, fluid volume, pH, epithelial integrity, and moisture. Moreover, the intensity of VVA symptoms (vaginal burning, vaginal itching, vaginal dryness, dyspareunia, and dysuria) was measured using a 10 cm visual analog scale (VAS), where the left extreme of the scale (score = 0) indicated "absence of symptom" and the right indicated "symptom as bad as it could be" (score = 100). Sexual function was evaluated with the Female Sexual Function Index (FSFI-19) questionnaire. The treatment was performed using a Leonardo Dual diode laser (Biolitec Italia Srl, Milano, Italy). The laser treatment consisted of three sessions, one per month. One month after the third session, the VHI, symptom VAS, and FSFI-19 were re-evaluated. In addition, the Patient Global Impression of Improvement (PGI-I) questionnaire was collected. RESULTS: Our study enrolled a total of 26 consecutive patients. All patients were either in menopause or under treatment with gonadotropin-releasing hormone (GnRH). None of the patients reported adverse effects after laser treatment. In total, 19 (73.1%) patients referred improvements of their symptoms according to PGI-I scores. All domains of the FSFI-19 questionnaire, significantly improved after the diode laser treatment. The mean VHI score increased by 3.2 points, from 12.2 to 15.4 (p < 0.001). Additionally, we documented a significant improvement in symptoms affecting the VAS score, from 69.2 to 43.5 points (p < 0.001). CONCLUSION: A diode vaginal laser is an effective and easily tolerated ambulatory procedure for vaginal functional restoration in the treatment of GSM and VVA.

Transvaginal excision of vaginal paraurethral leiomyoma: A video case report.

INTRODUCTION AND HYPOTHESIS: Vaginal leiomyomas are uncommon benign tumors of the genital district that appear as a circumscribed, mobile, and nontender mass along the vaginal tube. The gold standard of vaginal leiomyoma management is surgical treatment. We aimed to present a clinical case of vaginal leiomyoma successfully treated throughout a transvaginal excision and layered repair. METHODS: A 44-year-old woman was referred to our division for vaginal bulging symptoms and dyspareunia. Clinical examination revealed a 4-5 cm hard bulging mass in the anterior vaginal wall, below the urethra, compatible with vaginal leiomyoma. After proper counseling, the patient was admitted to transvaginal leiomyoma excision plus primary layered repair. RESULTS: No surgical complications were observed. The indwelling catheter was removed the day after the surgery. The patient was successfully discharged home on postoperative day 1. The patient is currently asymptomatic and there are no signs of recurrence. CONCLUSION: The procedure was successful in obtaining anatomical repair and relieving symptoms. This approach represents a valid procedure for the surgical management of this uncommon condition.

Epilepsy and nodding syndrome in association with an Onchocerca volvulus infection drive distinct immune profile patterns.

Previous studies have described the association of onchocerciasis (caused by Onchocerca volvulus) with epilepsy, including nodding syndrome, although a clear etiological link is still missing. Cases are found in different African countries (Tanzania, South Sudan, Uganda, Democratic Republic of the Congo, Central African Republic and Cameroon). In our study we investigated immunological parameters (cytokine, chemokine, immunoglobulin levels) in individuals from the Mahenge area, Tanzania, presenting with either epilepsy or nodding syndrome with or without O. volvulus infection and compared them to O. volvulus negative individuals from the same endemic area lacking neurological disorders. Additionally, cell differentiation was performed using blood smears and systemic levels of neurodegeneration markers, leiomodin-1 and N-acetyltyramine-O, ß-glucuronide (NATOG) were determined. Our findings revealed that cytokines, most chemokines and neurodegeneration markers were comparable between both groups presenting with epilepsy or nodding syndrome. However, we observed elevated eosinophil percentages within the O. volvulus positive epilepsy/nodding syndrome patients accompanied with increased eosinophilic cationic protein (ECP) and antigen-specific IgG levels in comparison to those without an O. volvulus infection. Furthermore, highest levels of NATOG were found in O. volvulus positive nodding syndrome patients. These findings highlight that the detection of distinct biomarkers might be useful for a differential diagnosis of epilepsy and nodding syndrome in O. volvulus endemic areas. Trial-registration: NCT03653975.

Efficacy and Adverse Effects After Single-Incision Slings for Women with Stress Urinary Incontinence: A 12-Year Follow-Up.

Objective: Single-incision slings (SISs) are not considered the first surgical choice for stress urinary incontinence due to few data about long-term results. Our aim was to evaluate the outcomes of SISs 12 years after implantation and to search for consequences such as deterioration after a certain amount of time. Methods: We included women with stress urinary incontinence both clinically and urodynamically proven who underwent SISs procedure. Objective and subjective cure rates were compared to short-term outcomes to detect possible deterioration over time. Results: A total of 85 patients were analysed with a median follow-up of 12.0 (IQR 10.4-12.8) years. Objective and subjective cure rates were 81.0% and 82.1%, respectively. Median (IQR) PGI-I scores and ICIQ-SF, respectively, were 1 (1-2) and 0 (0-6.8). No significant deterioration of outcomes over time was shown after comparison between short-term and long-term follow-ups (objective cure rate 84.5% vs 81.0%, p=0.684; subjective cure rates 92.9% vs 82.1%, p=0.060). Also, voiding symptoms and overactive bladder did not differ over time (20.2% vs 21.4%, p=1.000; 20.2% vs 33.3%, p=0.080, respectively). Conclusion: SISs were shown to be a procedure with a great efficacy and safety profile at very long-term follow-up.

Flat Magnetic Stimulation for Stress Urinary Incontinence: A 3-Month Follow-Up Study.

BACKGROUND: flat magnetic stimulation is based on a stimulation produced by electromagnetic fields with a homogenous profile. Patients with stress urinary incontinence (SUI) can take advantage of this treatment. We aimed to evaluate medium-term subjective, objective, and quality-of-life outcomes in patients with stress urinary incontinence to evaluate possible maintenance schedules. METHODS: a prospective evaluation through the administration of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the Incontinence Impact Questionnaire (IIQ7), and the Female Sexual Function Index (FSFI) was performed at three different time points: at the baseline (T0), at the end of treatment (T1), and at 3-month follow-up (T2). The stress test and the Patient Global Impression of Improvement questionnaire (PGI-I) defined objective and subjective outcomes, respectively. RESULTS: 25 consecutive patients were enrolled. A statistically significant reduction in the IIQ7 and ICIQ-SF scores was noticed at T1 returned to levels comparable to the baseline at T2. However, objective improvement remained significant even at a 3-month follow-up. Moreover, the PGI-I scores at T1 and T2 were comparable, demonstrating stable subjective satisfaction. CONCLUSION: despite a certain persistence of the objective and subjective continence improvement, the urinary-related quality of life decreases and returns to baseline values three months after the end of flat magnetic stimulation. These findings indicate that a further cycle of treatment is probably indicated after 3 months since benefits are only partially maintained after this timespan.

Spectrum of Helminth Infections in Migrants from Sub-Saharan Africa to Europe: A Literature Review.

Sub-Saharan Africa (SSA) is endemic to numerous neglected tropical diseases, including many helminth diseases. With the migration of people from this part of the world to Europe, as has been happening on a large scale since 2015, these diseases are becoming more relevant to European physicians. This work aims to summarize the recent literature on this topic and to raise awareness of helminth diseases afflicting SSA migrants. The databases PubMed, Embase, and MEDLINE were screened for literature published in English and German between January 1, 2015 and December 31, 2020. In total, 74 articles were included in this review. The spectrum of helminth infections in migrants from SSA found in the literature review is broad; current research, however, is particularly focused on infections with Schistosoma spp. and Strongyloides stercoralis. Both diseases are often characterized by a long course, with few or no symptoms, with the risk of long-term organ damage. Successful and reliable screening for schistosomiasis and strongyloidiasis is strongly recommended. However, the current diagnostic methods lack sensitivity and specificity, rendering the diagnosis challenging and reliable assessment of disease prevalence difficult. Novel diagnostic methods and a greater awareness of these diseases are urgently needed.

IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity.

The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6'-dimycolate (TDM). Recently, we found that IL-4 downregulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis. Here, we investigated functional consequences of IL-4 and helminth infection on MINCLE-driven macrophage activation and Th1/Th17 adjuvanticity. IL-4 inhibited MINCLE and cytokine induction after macrophage infection with Mycobacterium bovis bacille Calmette-Guerin (BCG). Infection of mice with BCG upregulated MINCLE on myeloid cells, which was inhibited by IL-4 plasmid injection and by infection with the nematode Nippostrongylus brasiliensis in monocytes. To determine the impact of helminth infection on MINCLE-dependent immune responses, we vaccinated mice with a recombinant protein together with the MINCLE ligand trehalose-6,6-dibehenate (TDB) as adjuvant. Concurrent infection with N. brasiliensis or with Schistosoma mansoni promoted T cell-derived IL-4 production and suppressed Th1/Th17 differentiation in the spleen. In contrast, helminth infection did not reduce Th1/Th17 induction by TDB in draining peripheral lymph nodes, where IL-4 levels were unaltered. Upon use of the TLR4-dependent adjuvant G3D6A, N. brasiliensis infection impaired selectively the induction of splenic antigen-specific Th1 but not of Th17 cells. Inhibition of MINCLE-dependent Th1/Th17 responses in mice infected with N. brasiliensis was dependent on IL-4/IL-13. Thus, helminth infection attenuated the Th17 response to MINCLE-dependent immunization in an organ- and adjuvant-specific manner via the Th2 cytokines IL-4/IL-13. Taken together, our results demonstrate downregulation of MINCLE expression on monocytes and macrophages by IL-4 as a possible mechanism of thwarted Th17 vaccination responses by underlying helminth infection.

Modulation of Host-Parasite Interactions with Small Molecules Targeting Schistosoma mansoni microRNAs.

Parasites use different strategies of communication with their hosts. One communication channel that has been studied in recent years is the use of vesicle microRNAs to influence the host immune system by trematodes. sma-microRNA-10, secreted from Schistosoma mansoni, has been shown to influence the fate of host T-cells through manipulation of the NF-κB pathway. We have identified low molecular weight tool compounds that can interfere with this microRNA-mediated manipulation of the host immune system. We used a fragment-based screening approach by means of nuclear magnetic resonance (NMR) to identify binders to the precursor of the parasite sma-microRNA-10 present in their extracellular vesicles. The small fragments identified were used to select larger molecules. These molecules were shown to counteract the inhibition of NF-κB activity by sma-microRNA-10 in cell-based assays.