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12 pages, 955 KiB  
Article
Single-Center Preliminary Experience Treating Endometrial Cancer Patients with Fiducial Markers
by Francesca Titone, Eugenia Moretti, Alice Poli, Marika Guernieri, Sarah Bassi, Claudio Foti, Martina Arcieri, Gianluca Vullo, Giuseppe Facondo, Marco Trovò, Pantaleo Greco, Gabriella Macchia, Giuseppe Vizzielli and Stefano Restaino
Life 2025, 15(8), 1218; https://doi.org/10.3390/life15081218 - 1 Aug 2025
Viewed by 186
Abstract
Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer [...] Read more.
Purpose: To present the findings of our preliminary experience using daily image-guided radiotherapy (IGRT) supported by implanted fiducial markers (FMs) in the radiotherapy of the vaginal cuff, in a cohort of post-surgery endometrial cancer patients. Methods: Patients with vaginal cuff cancer requiring adjuvant radiation with external beams were enrolled. Five patients underwent radiation therapy targeting the pelvic disease and positive lymph nodes, with doses of 50.4 Gy in twenty-eight fractions and a subsequent stereotactic boost on the vaginal vault at a dose of 5 Gy in a single fraction. One patient was administered 30 Gy in five fractions to the vaginal vault. These patients underwent external beam RT following the implantation of three 0.40 × 10 mm gold fiducial markers (FMs). Our IGRT strategy involved real-time 2D kV image-based monitoring of the fiducial markers during the treatment delivery as a surrogate of the vaginal cuff. To explore the potential role of FMs throughout the treatment process, we analyzed cine movies of the 2D kV-triggered images during delivery, as well as the image registration between pre- and post-treatment CBCT scans and the planning CT (pCT). Each CBCT used to trigger fraction delivery was segmented to define the rectum, bladder, and vaginal cuff. We calculated a standard metric to assess the similarity among the images (Dice index). Results: All the patients completed radiotherapy and experienced good tolerance without any reported acute or long-term toxicity. We did not observe any loss of FMs during or before treatment. A total of twenty CBCTs were analyzed across ten fractions. The observed trend showed a relatively emptier bladder compared to the simulation phase, with the bladder filling during the delivery. This resulted in a final median Dice similarity coefficient (DSC) of 0.90, indicating strong performance. The rectum reproducibility revealed greater variability, negatively affecting the quality of the delivery. Only in two patients, FMs showed intrafractional shift > 5 mm, probably associated with considerable rectal volume changes. Target coverage was preserved due to a safe CTV-to-PTV margin (10 mm). Conclusions: In our preliminary study, CBCT in combination with the use of fiducial markers to guide the delivery proved to be a feasible method for IGRT both before and during the treatment of post-operative gynecological cancer. In particular, this approach seems to be promising in selected patients to facilitate the use of SBRT instead of BRT (brachytherapy), thanks to margin reduction and adaptive strategies to optimize dose delivery while minimizing toxicity. A larger sample of patients is needed to confirm our results. Full article
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13 pages, 538 KiB  
Article
Stereotactic Body Radiotherapy for the Treatment of Oligometastases Located in the Peritoneum or in the Abdominal Wall: Preliminary Results from a Mono-Institutional Analysis
by Francesco Cuccia, Salvatore D’Alessandro, Marina Campione, Vanessa Figlia, Gianluca Mortellaro, Antonio Spera, Giulia Musicò, Antonino Abbate, Salvatore Russo, Carlo Messina, Giuseppe Carruba, Livio Blasi and Giuseppe Ferrera
J. Pers. Med. 2025, 15(7), 312; https://doi.org/10.3390/jpm15070312 - 14 Jul 2025
Viewed by 435
Abstract
Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit [...] Read more.
Purpose/Objective(s): Peritoneal carcinosis can occur in several gastrointestinal or gynecological malignancies and its prognosis is usually poor. With the advent of more effective systemic agents, the overall survival of metastatic patients has been revolutionized and isolated peritoneal or abdominal wall metastases might benefit from local treatments; Stereotactic Body Radiotherapy (SBRT) might be considered in selected patients with oligometastatic presentation. Materials/Methods: Oligometastases were defined according to recent ESTRO/EORTC consensus. Inclusion criteria were as follows: ECOG PS ≤ 2, written informed consent, up to five lesions to be treated at the same time, patients treated with radiotherapy schedules applying minimum 6 Gy per fraction. The primary endpoint of the study was local control (LC); acute and late toxicity, distant progression-free survival (DPFS), time-to-next systemic treatment (TNST), polymetastatic-free survival (PMFS) and overall survival (OS) were secondary endpoints. Toxicity was assessed according to CTCAE criteria v5.0. Statistical associations between clinical variables and outcomes were assessed using Fisher’s exact test, and Kruskal–Wallis test, as appropriate. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Between April 2020 and September 2024 a total of 26 oligometastatic lesions located in the peritoneum or in the abdominal wall detected in 20 patients received SBRT with Helical Tomotherapy. All cases have been assessed by a multidisciplinary team. Only in three patients out of twenty did more than one lesion receive SBRT: two lesions in two patients, and five lesions in a single case of colorectal cancer with ongoing third-line systemic treatment. Median total dose was 30 Gy (27–35 Gy) in five fractions (3–5). The most frequent primary neoplasm was ovarian cancer in 14/20, endometrial in 2/20, while the remaining were colorectal, vaginal, pancreatic and non-small cell lung cancer. Four lesions were located in the abdominal wall, while the remaining twenty-two were located in the peritoneum. Concurrent systemic therapy was administered in 18/20 patients. With a median follow-up of 15 months (range, 6–59), our 1-year LC was 100%, while 1-year DPFS, PMFS, TNTS and OS rates were 54%, 69%, 61% and 83%, respectively. Abdominal wall location and treatment of a subsequent oligometastatic recurrence with a second course of SBRT were both significantly associated with improved OS (p = 0.03 and p = 0.04, respectively). No G ≥ 3 adverse events occurred. Conclusion: Our preliminary data support the use of SBRT in selected cases of oligometastatic disease located in the peritoneum or in the abdominal wall with excellent results in terms of tolerability and promising clinical outcomes. Full article
(This article belongs to the Special Issue Personalized Diagnosis and Treatment of Oligometastatic Disease)
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20 pages, 2740 KiB  
Article
Antistatic Melt-Electrowritten Biodegradable Mesh Implants for Enhanced Pelvic Organ Prolapse Repair
by Daniela Cruz, Francisca Vaz, Evangelia Antoniadi, Ana Telma Silva, Joana Martins, Fábio Pinheiro, Nuno Miguel Ferreira, Luís B. Bebiano, Rúben F. Pereira, António Fernandes and Elisabete Silva
Appl. Sci. 2025, 15(14), 7763; https://doi.org/10.3390/app15147763 - 10 Jul 2025
Viewed by 344
Abstract
Pelvic organ prolapse (POP) is a health condition that can significantly impact patients’ quality of life. Unfortunately, most available treatments present drawbacks such as high recurrence rates, risk of complications, poor tissue integration, and the need for reintervention. One promising alternative is the [...] Read more.
Pelvic organ prolapse (POP) is a health condition that can significantly impact patients’ quality of life. Unfortunately, most available treatments present drawbacks such as high recurrence rates, risk of complications, poor tissue integration, and the need for reintervention. One promising alternative is the use of biodegradable implantable meshes, which can support the organs, guide tissue regeneration, and be fully absorbed without damaging the surrounding tissues. In this study, biodegradable polycaprolactone (PCL) meshes were fabricated using melt electrowritten (MEW), incorporating the antistatic agent Hostastat® FA 38 (HT) to address these limitations. The goal was to produce microscaffolds with suitable biophysical properties, particularly more stable fiber deposition and reduced fiber diameter. Different HT concentrations (0.03, 0.06, and 0.1 wt%) were investigated to assess their influence on the fiber diameter and mechanical properties of the PCL meshes. Increasing HT concentration significantly reduced fiber diameter by 14–17%, 39–45%, and 65–66%, depending on mesh geometry (square or sinusoidal). At 0.06 wt%, PCL/HT meshes showed a 24.10% increase in tensile strength and a 55.59% increase in Young’s Modulus compared to pure PCL meshes of similar diameter. All formulations demonstrated cell viability >90%. Differential scanning calorimetry (DSC) revealed preserved thermal stability and changes in crystallinity with HT addition. These findings indicate that the antistatic agent yields promising results, enabling the production of thinner, more stable fibers with higher tensile strength and Young’s Modulus than PCL meshes, without adding cellular toxicity. Developing a thinner and more stable mesh that mimics vaginal tissue mechanics could offer an innovative solution for POP repair. Full article
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17 pages, 2888 KiB  
Article
Investigating the Influence of Body Mass Index on Organs at Risk Doses for Adjuvant High-Dose-Rate Vaginal Cuff Brachytherapy in Patients with Early-Stage Endometrial Carcinoma: A Single-Center Experience
by Alexandra Timea Kirsch-Mangu, Diana Cristina Pop, Alexandru Țipcu, Andrei-Rareș Avasi, Claudia Ordeanu, Ovidiu Florin Coza and Alexandru Irimie
Diagnostics 2025, 15(7), 795; https://doi.org/10.3390/diagnostics15070795 - 21 Mar 2025
Viewed by 615
Abstract
Background: Endometrial cancer is the most common gynecologic malignancy in developed countries, with obesity recognized as a major risk factor contributing to its incidence. The rising prevalence of obesity has significant implications for treatment planning, particularly in radiation therapy approaches such as [...] Read more.
Background: Endometrial cancer is the most common gynecologic malignancy in developed countries, with obesity recognized as a major risk factor contributing to its incidence. The rising prevalence of obesity has significant implications for treatment planning, particularly in radiation therapy approaches such as high-dose-rate (HDR) vaginal cuff brachytherapy, which is commonly used as adjuvant therapy in early-stage endometrial carcinoma. Body Mass Index (BMI) is a key factor in brachytherapy, as increased adiposity may alter dosimetric parameters, affecting radiation distribution and doses received by organs at risk (OARs). Understanding the correlation between BMI and radiation dose to OARs is essential for optimizing treatment planning and minimizing adverse effects. Identifying dose variations across different BMI categories may help refine patient-specific brachytherapy approaches to ensure both efficacy and safety. Objectives: This study aims to investigate the influence of Body Mass Index (BMI) on the doses received by organs at risk (OAR) during high-dose-rate (HDR) vaginal cuff brachytherapy in patients diagnosed with early-stage endometrial carcinoma. Understanding the relationship between BMI and OAR doses could enhance treatment planning and minimize complications. Methods: We collected brachytherapy data for 242 endometrial cancer patients treated with adjuvant HDR vaginal cuff brachytherapy. The patients were categorized based on their BMI into normal weight, overweight, and obese groups. Dosimetric data were collected for OARs, including the bladder, rectum, and sigmoid colon, and also for dose fractionation, D90%, and the active length of the brachytherapy cylinder. The analysis included comparing the doses received by each organ across different BMI categories using appropriate statistical methods. Results: Preliminary findings indicated a significant variation in the doses to OARs correlating with BMI classifications. Obese patients exhibited slightly higher mean doses to the rectum and sigmoid compared to those with a normal BMI. The statistical analysis demonstrated that as BMI increased, the dose to these organs at risk also tended to increase, suggesting a need for adjusted treatment planning strategies in this population. Conclusions: Obesity is a key concern in endometrial cancer patients, with higher BMI linked to slightly increased doses to the rectum and sigmoid, though treatment remained homogeneously delivered. Future prospective clinical studies are essential to explore the relationship between these dosimetric findings, specifically the correlation between higher BMI, increased doses to organs at risk (OARs), and late treatment-related toxicities. This research is needed to better understand the long-term implications and to optimize therapeutic outcomes. Full article
(This article belongs to the Special Issue Advances in Diagnosis of Gynecological Cancers)
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18 pages, 5032 KiB  
Article
Electrospun Coaxial Polycaprolactone/Polyvinylpyrrolidone Fibers Containing Cisplatin: A Potential Local Chemotherapy Delivery System for Cervical Cancer Treatment
by Mariana Sarai Silva-López, Vladimir Alonso Escobar-Barrios and Luz Eugenia Alcántara-Quintana
Polymers 2025, 17(5), 637; https://doi.org/10.3390/polym17050637 - 27 Feb 2025
Cited by 1 | Viewed by 922
Abstract
Cisplatin, a frequently used chemotherapeutic for the treatment of cervical cancer, causes adverse effects that limit its use. Treatment with local therapy that limits toxicity remains a challenge. The aim of this study was to develop a local intravaginal cisplatin delivery system of [...] Read more.
Cisplatin, a frequently used chemotherapeutic for the treatment of cervical cancer, causes adverse effects that limit its use. Treatment with local therapy that limits toxicity remains a challenge. The aim of this study was to develop a local intravaginal cisplatin delivery system of polycaprolactone/polyvinylpyrrolidone sheath/core fibers by coaxial electrospinning. Physicochemical properties, degradation rate, mucoadhesion, release profile, and in vitro biosafety assays were characterized. Microscopy images confirmed the coaxial nature of the fibers and showed continuous morphology and diameters of 3–9 µm. The combination of polymers improved their mechanical properties. The contact angle < 85° indicated a hydrophilic surface, which would allow its dissolution in the vaginal environment. The release profile showed a rapid initial release followed by a slow and sustained release over eight days. The degradation test showed ~50% dissolution of the fibers on day 10. The adhesion of the fibrous device to the vaginal wall lasted for more than 15 days, which was sufficient time to allow the release of cisplatin. The biosafety tests showed great cytocompatibility and no hemolysis. The characteristics of the developed system open the possibility of its application as a localized therapy against cervical cancer, reducing adverse effects and improving the quality of life of patients. Full article
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9 pages, 1350 KiB  
Article
Bulgarian Experience in Vaginal Electronic Brachytherapy for Gynecologic Cancers’ Treatment—First Results
by Virginia Payakova, Angel Yordanov, Desislava Kostova-Lefterova, Nikolay Mutkurov, Ilko Iliev, Marin Valkov, Elitsa Encheva and Desislava Hitova-Topkarova
J. Clin. Med. 2024, 13(24), 7849; https://doi.org/10.3390/jcm13247849 - 23 Dec 2024
Viewed by 1126
Abstract
Background/Objectives: The objective of this study is to prospectively collect dosimetric and clinical data on vaginal cuff electronic brachytherapy and propose a protocol for the procedure. Methods: Twenty-five patients who had proven endometrial or cervical carcinoma and had undergone radical hysterectomy have [...] Read more.
Background/Objectives: The objective of this study is to prospectively collect dosimetric and clinical data on vaginal cuff electronic brachytherapy and propose a protocol for the procedure. Methods: Twenty-five patients who had proven endometrial or cervical carcinoma and had undergone radical hysterectomy have been treated with vaginal cuff electronic brachytherapy. Treatment session durations and doses to the targets and the organs at risk have been extracted from the treatment planning software. Patients have been followed up for early side effects for 3 months. Results: Treatment session times ranged from 3.0 to 6.6 min. Mean coverage of the planned treatment volume with 100% of the prescribed dose was 90%, and with 95% of the prescribed dose was 95%. Doses in the bladder were lower than those achieved in previously published studies with a mean D2cc of 4.7 Gy, and doses in the rectum were higher with a mean D2cc of 5.3 Gy. The first-month adverse events included eight G1 and three G2 toxicities, while the events registered on the third month were two G2 vaginal dryness events and one G1 urinary tract obstruction, of which only one patient with vaginal dryness did not respond to local treatment. No local relapses have been detected. Conclusions: Vaginal cuff electronic brachytherapy has demonstrated safety and effectiveness. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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25 pages, 4332 KiB  
Article
Development and Characterization of Sodium Bicarbonate-Based Gel for Cytolytic Vaginosis
by Carlos Gaspar, Ana Sofia Agonia, Sara Felício, Mariana Tomás, Diana Esteves, Rita Palmeira-de-Oliveira, Gilbert G. G. Donders, José Martinez-de-Oliveira and Ana Palmeira-de-Oliveira
Pharmaceutics 2024, 16(11), 1436; https://doi.org/10.3390/pharmaceutics16111436 - 11 Nov 2024
Cited by 2 | Viewed by 1890
Abstract
Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. [...] Read more.
Background/Objectives: Cytolytic vaginosis or, classically, Doderlein’s cytolysis is characterized by significant growth of species of the Lactobacillus genus, which leads to high amounts of lactic acid in the vaginal environment. Lactobacillus crispatus has been proposed as a key pathogen in this clinical condition. The symptomatology of cytolytic vaginosis is commonly confused with that of vulvovaginal candidosis, leading to inadequate and ineffective azole therapies. Nevertheless, historically, the use of sodium bicarbonate intimate baths was an effective way to reduce the symptoms of cytolytic vaginosis. Methods: In this study, four HPMC gel prototypes were developed, containing sodium bicarbonate concentrations ranging from 4% to 7% (w/w). These gels were evaluated for their physicochemical properties, antimicrobial activity, interference with lactobacilli adhering to cells, and cellular and tissue biocompatibility. Results: The gels presented pH values of around 9.0, and osmolality between 706 mOsm/kg (F4) and 1065 mOsm/kg (F7). The viscosity upon heating to physiologic temperature and dilution with simulated vaginal fluid was highly affected by the concentration of sodium bicarbonate. Gels with higher sodium bicarbonate concentrations (F6 and F7) were not shown to be stable in these conditions. All formulations exhibited effective antimicrobial activity against seven L. crispatus strains, with MIC values ranging from 6.25% to 25% (v/v) in terms of dilution. Additionally, the 4% (w/w) gel significantly interfered with the adhesion of L. crispatus to epithelial cells in competition and exclusion assays, reducing adhesion by more than 90% in relation to the control. Cytotoxicity tests on the Hec-1A, HeLa, and VK2/E6E7 cell lines indicated that the F4 and F5 gels demonstrated lower cytotoxicity levels compared to those with higher concentrations. Furthermore, ex vivo assays using porcine vaginal tissue confirmed that the 4% gel was non-toxic at a 25% (v/v) dilution. Conclusions: Based on these results, the 4% (w/w) sodium bicarbonate gel (F4) emerges as a promising therapeutic option for cytolytic vaginosis, offering effective bacterial interference, favourable physicochemical properties, and biocompatibility suitable for vaginal application. Full article
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14 pages, 943 KiB  
Article
Implementation of Primary Immune Thrombocytopenia Clinical Practice Guidelines for Management of Pregnancy
by Amanda J. Llaneza, Laura A. Beebe, Janis E. Campbell, Marshall K. Cheney, Ying Zhang and Deirdra R. Terrell
J. Clin. Med. 2024, 13(21), 6477; https://doi.org/10.3390/jcm13216477 - 29 Oct 2024
Cited by 1 | Viewed by 2119
Abstract
Background: Managing primary immune thrombocytopenia (ITP) in pregnancy is challenging. Providers must balance bleeding risk against medication toxicity. The evaluation of the implementation of pregnancy-specific ITP clinical guidelines has not been widely studied. The goal of this study was to describe the implementation [...] Read more.
Background: Managing primary immune thrombocytopenia (ITP) in pregnancy is challenging. Providers must balance bleeding risk against medication toxicity. The evaluation of the implementation of pregnancy-specific ITP clinical guidelines has not been widely studied. The goal of this study was to describe the implementation of pregnancy-specific ITP guidelines at an academic health center. Methods: We conducted a retrospective chart review at the University of Oklahoma Health system from 2011 to 2020. Descriptive statistics were calculated to summarize the characteristics of the study population. Management, according to the clinical guidelines (American Society of Hematology; American College of Obstetricians and Gynecologists) was evaluated during pregnancy and during/for delivery. Results: A total of 85 pregnant persons with ITP were included. The majority (68%; 58/85) delivered vaginally. There were 0 maternal deaths and 2 infant deaths. No patients had major bleeding during pregnancy. Postpartum hemorrhage was experienced by 14%. The management of thrombocytopenia during pregnancy was 100% adherent to the strong recommendation for severe (n = 13) and mild (n = 11) thrombocytopenia. However, 18/50 (36%) asymptomatic persons with moderate thrombocytopenia received treatment despite the strong recommendation that treatment was unnecessary. Additionally, 8/21 (38%) persons with moderate thrombocytopenia received treatment to increase platelet counts for epidural anesthesia despite the guideline’s suggestion that it was unnecessary. Conclusions: During pregnancy, patients with severe thrombocytopenia (i.e., most at risk of bleeding) received treatment. On the other hand, approximately 40% of pregnant persons with ITP received unnecessary treatment for moderate asymptomatic thrombocytopenia either during pregnancy or for an epidural. Utilizing clinical practice guidelines would reduce the overtreatment of pregnant persons which would reduce the potential side effects of therapy for the mother and infant. Full article
(This article belongs to the Special Issue Clinical Management of Platelet Disorders)
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33 pages, 10254 KiB  
Systematic Review
Schistosomiasis–Microbiota Interactions: A Systematic Review and Meta-Analysis
by Philip Afful, Godwin Kwami Abotsi, Czarina Owusua Adu-Gyamfi, George Benyem, Gnatoulma Katawa, Samuel Kyei, Kathrin Arndts, Manuel Ritter and Kwame Kumi Asare
Pathogens 2024, 13(10), 906; https://doi.org/10.3390/pathogens13100906 - 16 Oct 2024
Cited by 2 | Viewed by 4447
Abstract
Introduction: Schistosomiasis, a tropical disease affecting humans and animals, affected 251.4 million people in 2021. Schistosoma mansoni, S. haematobium, S. intercalatum, and S. japonicum are primary human schistosomes, causing tissue damage, granulomas, ulceration, hemorrhage, and opportunistic pathogen entry. The gut [...] Read more.
Introduction: Schistosomiasis, a tropical disease affecting humans and animals, affected 251.4 million people in 2021. Schistosoma mansoni, S. haematobium, S. intercalatum, and S. japonicum are primary human schistosomes, causing tissue damage, granulomas, ulceration, hemorrhage, and opportunistic pathogen entry. The gut and urinary tract microbiota significantly impact a host’s susceptibility to schistosomiasis, disrupting microbial balance; however, this relationship is not well understood. This systematic review and meta-analysis explores the intricate relationship between schistosomiasis and the host’s microbiota, providing crucial insights into disease pathogenesis and management. Methods: This systematic review used PRISMA guidelines to identify peer-reviewed articles on schistosomiasis and its interactions with the host microbiome, using multiple databases and Google Scholar, providing a robust dataset for analysis. The study utilized Meta-Mar v3.5.1; descriptive tests, random-effects models, and subgroups were analyzed for the interaction between Schistosomiasis and the microbiome. Forest plots, Cochran’s Q test, and Higgins’ inconsistency statistic (I2) were used to assess heterogeneity. Results: The human Schistosoma species were observed to be associated with various bacterial species isolated from blood, stool, urine, sputum, skin, and vaginal or cervical samples. A meta-analysis of the interaction between schistosomiasis and the host microbiome, based on 31 studies, showed 29,784 observations and 5871 events. The pooled estimates indicated a significant association between schistosomiasis and changes in the microbiome of infected individuals. There was considerable heterogeneity with variance effect sizes (p < 0.0001). Subgroup analysis of Schistosoma species demonstrated that S. haematobium was the most significant contributor to the overall heterogeneity, accounting for 62.1% (p < 0.01). S. mansoni contributed 13.0% (p = 0.02), and the coinfection of S. haematobium and S. mansoni accounted for 16.8% of the heterogeneity (p < 0.01), contributing to the variability seen in the pooled analysis. Similarly, praziquantel treatment (RR = 1.68, 95% CI: 1.07–2.64) showed high heterogeneity (Chi2 = 71.42, df = 11, p < 0.01) and also indicated that Schistosoma infections in males (RR = 1.46, 95% CI: 0.00 to 551.30) and females (RR = 2.09, 95% CI: 0.24 to 18.31) have a higher risk of altering the host microbiome. Conclusions: Schistosomiasis significantly disrupts the host microbiota across various bodily sites, leading to increased susceptibility to different bacterial taxa such as E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Staphylococcus, Streptococcus, and Mycobacterium species (M. tuberculosis and M. leprae). This disruption enables these bacteria to produce toxic metabolites, which in turn cause inflammation and facilitate the progression of disease. The impact of schistosomiasis on the vaginal microbiome underscores the necessity for gender-specific approaches to treatment and prevention. Effective management of female genital schistosomiasis (FGS) requires addressing both the parasitic infection and the resulting microbiome imbalances. Additionally, praziquantel-treated individuals have different microbiome compositions compared to individuals with no praziquantel treatment. This suggests that combining praziquantel treatment with probiotics could potentially decrease the disease severity caused by an altered microbiome. Full article
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9 pages, 243 KiB  
Article
Relationship between the Presence of Human Papillomavirus in the Female Urethra and Recurrent Urinary Tract Infections
by Cristina Mena-Ruiz, Julius Jan Szczesnieski, Magaly Márquez-Sánchez, Bárbara-Yolanda Padilla-Fernández, Javier Flores-Fraile and María-Fernanda Lorenzo-Gómez
J. Clin. Med. 2024, 13(17), 5329; https://doi.org/10.3390/jcm13175329 - 9 Sep 2024
Viewed by 4606
Abstract
Introduction: Recurrent urinary tract infections (rUTIs) are highly prevalent health issues among women, significantly impacting their quality of life. Urethral pain or urethritis can arise from infectious or non-infectious origins. The presence of Human Papillomavirus (HPV) in the urogenital tract has been associated [...] Read more.
Introduction: Recurrent urinary tract infections (rUTIs) are highly prevalent health issues among women, significantly impacting their quality of life. Urethral pain or urethritis can arise from infectious or non-infectious origins. The presence of Human Papillomavirus (HPV) in the urogenital tract has been associated with high-risk sexual behaviors, but its presence in the female urethra without such behaviors has not been thoroughly investigated. Objectives: The study aims to determine the presence of HPV in the urethra of women with recurrent urinary tract infections (rUTIs) and concomitant urethral syndrome and to compare the clinical and microbiological characteristics of women with and without urethral HPV, specifically focusing on those without high-risk sexual behaviors. Methods: This prospective multicenter study included 138 women over 18 years old with rUTIs and concomitant urethral pain syndrome. High-risk sexual behaviors, sexually transmitted infections, and vaginitis were set as exclusion criteria. Participants were divided into two groups: NHPV (n = 72) with no urethral HPV and HPV (n = 66) with urethral HPV presence. Variables analyzed included age, body mass index (BMI), follow-up duration, comorbidities, treatments, toxic habits, surgical history, main symptoms, urine sediment findings, and cultures from urine and vaginal exudate. HPV genotyping was also performed. Descriptive statistics were used, along with Student’s t-test, Chi-square, Fisher’s exact test, ANOVA, and multivariate cluster analysis. Results: The NHPV group was older on average (48.75 years) compared to the HPV group (39.09 years). The HPV group had a longer follow-up period (2634 days vs. 1975 days in NHPV). Urinary incontinence was significantly more common in NHPV (63.89%) compared to HPV (18.18%) (p = 0.001). HPV-positive women had a higher prevalence of verrucous lesions in the vaginal introitus (64% vs. 8% in NHPV). Additionally, the HPV group showed higher rates of pyuria (27.27%), vaginal Candida albicans (36.26%), and positive urine cultures for Escherichia coli (47.83%), Enterococcus faecalis (36.36%), and Klebsiella pneumoniae (21.74%). No significant differences were observed between the groups concerning BMI, smoking habits, diabetes, or the main symptom at consultation. The most common HPV genotypes identified were G35, G42, and G66 (each 27%). Multivariate analysis revealed that sensitivity to nitrofurantoin was the most significant variable in the HPV group (importance of 0.96), followed by fosfomycin (0.79), trimethoprim (0.79), and amoxicillin (0.71). Conclusions: HPV was present in the urethra of 47.8% of women with rUTIs and concomitant urethral syndrome who did not exhibit high-risk sexual behaviors. These women were younger and had a longer duration of symptoms compared to those without urethral HPV. The identification of Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae was more common in the HPV group. The sensitivity of bacteria to nitrofurantoin and fosfomycin is crucial for the clinical management of these patients. The presence of urethral HPV should be considered in the evaluation and treatment of women with rUTIs and urethral syndrome. Full article
(This article belongs to the Section Nephrology & Urology)
13 pages, 1049 KiB  
Article
Impact of Vaginal Dilator Use and 68 Gy EQD2(α/β=3) Dose Constraint on Vaginal Complications in External Beam Irradiation Followed by Brachytherapy in Post-Operative Endometrial Cancer
by Faegheh Noorian, Rosa Abellana, Yaowen Zhang, Antonio Herreros, Valentina Lancellotta, Luca Tagliaferri, Sebastià Sabater, Aureli Torne, Eduard Agusti-Camprubi and Angeles Rovirosa
J. Pers. Med. 2024, 14(8), 838; https://doi.org/10.3390/jpm14080838 - 8 Aug 2024
Cited by 1 | Viewed by 1396
Abstract
Background: This study evaluated the clinical outcomes of applying a 68 Gy EQD2(α/β=3) dose constraint to the most exposed 2 cm3 area of the vagina in post-operative endometrial cancer patients treated with vaginal-cuff brachytherapy after external beam irradiation and the impact [...] Read more.
Background: This study evaluated the clinical outcomes of applying a 68 Gy EQD2(α/β=3) dose constraint to the most exposed 2 cm3 area of the vagina in post-operative endometrial cancer patients treated with vaginal-cuff brachytherapy after external beam irradiation and the impact of vaginal dilator use on late vaginal complications. Material and methods: We analyzed 131 patients treated with vaginal-cuff brachytherapy after external beam irradiation. Group-1 (65 patients) received one fraction of 7 Gy, and Group-2 (66 patients) received one fraction of between 5.5 and 7.0 Gy after applying a 68 Gy EQD2(α/β=3) dose constraint. Vaginal-cuff relapse, late toxicity, clinical target volume, vaginal dilator use, D90, and EQD2(α/β=3) at 2 cm3 of the most exposed part of the clinical target volume were evaluated. Descriptive analysis, the chi-squared test, Student’s t-test, and the Cox proportional and Kaplan–Meier models were used for the statistical analysis. Results: With a median follow-up of 60 months, the vaginal-cuff relapse rate was 1/131 (0.8%). Late vaginal complications appeared in 36/65 (55.4%) Group-1 patients and 17/66 (25.8%) Group-2 patients (p = 0.003). Multivariate analysis showed that belonging to Group-1 and vaginal dilator use of <9 months were independent prognostic factors of late vaginal complications with hazard ratios of 1.99 (p = 0.021) and 3.07 (p = 0.010), respectively. Conclusions: A 68 Gy EQD2(α/β=3) constraint at 2 cm3 of clinical target volume and vaginal dilator use of ≥9 months were independent prognostic factors, having protective effects on late vaginal complications. Full article
(This article belongs to the Special Issue Obstetrics and Gynecology and Women's Health—2nd Edition)
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23 pages, 4946 KiB  
Article
Next-Generation Contraceptive Intravaginal Ring: Comparison of Etonogestrel and Ethinyl Estradiol In Vitro and In Vivo Release from 3D-Printed Intravaginal Ring and NuvaRing
by Isabella C. Young, Allison L. Thorson, Mackenzie L. Cottrell, Craig Sykes, Amanda P. Schauer, Rani S. Sellers, Rima Janusziewicz, Kathleen L. Vincent and Soumya Rahima Benhabbour
Pharmaceutics 2024, 16(8), 1030; https://doi.org/10.3390/pharmaceutics16081030 - 2 Aug 2024
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Abstract
Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface [...] Read more.
Intravaginal rings (IVRs) represent a well-established, woman-controlled and sustained vaginal drug delivery system suitable for a wide range of applications. Here, we sought to investigate the differences in etonogestrel (ENG) and ethinyl estradiol (EE) release from a 3D-printed IVR utilizing continuous liquid interface production (CLIP™) (referred to as CLIPLOW for low drug loading and CLIPHIGH IVRs for high drug loading) and NuvaRing, a commercially available injection molded IVR. We conducted in vitro release studies in simulated vaginal fluid to compare the release of ENG and EE from CLIPLOW IVRs and NuvaRing. CLIPLOW IVRs had a similar hormone dose to NuvaRing and exhibited slightly slower ENG release and greater EE release in vitro compared to NuvaRing. When administered to female sheep, NuvaRing demonstrated greater ENG/EE levels in plasma, vaginal tissue and vaginal fluids compared to CLIPLOW IVR despite similar drug loadings. Leveraging observed hormones levels in sheep from NuvaRing as an effective contraceptive benchmark, we developed a long-acting CLIPHIGH IVR with increased ENG and EE doses that demonstrated systemic and local hormone levels greater than the NuvaRing for 90 days in sheep. No signs of toxicity were noted regarding general health, colposcopy, or histological analysis in sheep after CLIPHIGH IVR administration. Our results provided (1) a comparison of ENG and EE release between a 3D-printed IVR and NuvaRing in vitro and in vivo, (2) a preclinical pharmacokinetic benchmark for vaginally delivered ENG and EE and (3) the generation of a 90-day CLIP IVR that will be utilized in future work to support the development of a long-acting ENG/EE IVR combined with an antiretroviral for the prevention of HIV and unplanned pregnancy. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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13 pages, 833 KiB  
Article
Adjuvant Treatment of Stage I–II Serous Endometrial Cancer: A Single Institution 20-Year Experience
by Aquila Akingbade, François Fabi, Rodrigo Cartes, James Tsui and Joanne Alfieri
Curr. Oncol. 2024, 31(7), 3758-3770; https://doi.org/10.3390/curroncol31070277 - 29 Jun 2024
Viewed by 2891
Abstract
Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All [...] Read more.
Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I–II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan–Meier estimates and Cox’s proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04–0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07–0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options. Full article
(This article belongs to the Special Issue Radiation Therapy for Gynecological Cancer)
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18 pages, 3690 KiB  
Article
Higher Concentrations of Essential Trace Elements in Women Undergoing IVF May Be Associated with Poor Reproductive Outcomes Following Single Euploid Embryo Transfer
by Roberto Gonzalez-Martin, Andrea Palomar, Silvia Perez-Deben, Stefania Salsano, Alicia Quiñonero, Laura Caracena, Rocio Fernandez-Saavedra, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Juan Giles, Carmen Vidal, Jose Bellver and Francisco Dominguez
Cells 2024, 13(10), 839; https://doi.org/10.3390/cells13100839 - 15 May 2024
Cited by 3 | Viewed by 2241
Abstract
Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical [...] Read more.
Essential trace elements are micronutrients whose deficiency has been associated with altered fertility and/or adverse pregnancy outcomes, while surplus may be toxic. The concentrations of eight essential trace elements were measured using inductively coupled mass spectrometry (ICP-MS) and assessed with respect to clinical in vitro fertilization (IVF) outcomes in a population of 51 women undergoing IVF with intracytoplasmic sperm injection (ICSI), pre-implantation genetic screening for aneuploidy (PGT-A), and single frozen euploid embryo transfer (SET/FET). Specifically, copper (Cu), zinc (Zn), molybdenum, selenium, lithium, iron, chromium, and manganese were quantified in follicular fluid and whole blood collected the day of vaginal oocyte retrieval (VOR) and in urine collected the day of VOR and embryo transfer. We found that the whole blood Cu/Zn ratio was significantly associated with superior responses to ovarian stimulation. Conversely, the whole blood zinc and selenium concentrations were significantly associated with poor ovarian response outcomes. Higher levels of whole blood zinc and selenium, urinary selenium, lithium, and iron had significant negative associations with embryologic outcomes following IVF. Regarding clinical IVF outcomes, higher urinary molybdenum concentrations the day of VOR were associated with significantly lower odds of implantation and live birth, while higher urinary Cu/Mo ratios on the day of VOR were associated with significantly higher odds of implantation, clinical pregnancy, and live birth. Our results suggest that essential trace element levels may directly influence the IVF outcomes of Spanish patients, with selenium and molybdenum exerting negative effects and copper-related ratios exerting positive effects. Additional studies are warranted to confirm these relationships in other human populations. Full article
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15 pages, 463 KiB  
Systematic Review
Optimizing Palliative Pelvic Radiotherapy in Gynecological Cancers: A Systematic Review and Analysis
by Beatrice Anghel, Mihai-Teodor Georgescu, Crenguta Sorina Serboiu, Andreea Nicoleta Marinescu, Cătălin Aliuș, Dragoș-Eugen Georgescu, Bogdan Mocanu, Sabina Sucuri and Anca Daniela Stanescu
Diagnostics 2024, 14(5), 547; https://doi.org/10.3390/diagnostics14050547 - 5 Mar 2024
Cited by 2 | Viewed by 2848
Abstract
Background: Palliative radiotherapy plays a crucial role in managing symptomatic gynecological cancers (GCs). This article aims to systematically review literature studies on palliative pelvic radiotherapy in cervical, endometrial, ovarian, vaginal, and vulvar cancers. The primary focus is centered around evaluating symptom relief, quality [...] Read more.
Background: Palliative radiotherapy plays a crucial role in managing symptomatic gynecological cancers (GCs). This article aims to systematically review literature studies on palliative pelvic radiotherapy in cervical, endometrial, ovarian, vaginal, and vulvar cancers. The primary focus is centered around evaluating symptom relief, quality of life (QOL), and toxicity in order to ascertain optimal radiotherapy regimens. Methodology: For this thorough review, we mainly relied on Medline to gather papers published until November 2023. Selected studies specifically detailed symptomatology and QOL responses in palliative pelvic radiotherapy used for GCs. Results: Thirty-one studies, mostly retrospective studies and those lacking standardized outcome measures, showed varied responses. Encouraging outcomes were noted in managing hemorrhage (55%) and pain control (70%). However, comprehensively assessing overall symptom response rates and toxicity remained challenging. Investigations into 10 Gy fractionation revealed benefits in addressing tumor-related bleeding and pain in female genital tract cancers. Conclusions: Palliative pelvic radiotherapy effectively manages symptomatic GCs. Nonetheless, unresolved dosing and fractionation considerations warrant further investigation. Embracing modern therapies alongside radiotherapy offers improved symptom control, emphasizing the importance of selecting suitable patients for successful GC palliation interventions. Full article
(This article belongs to the Special Issue Diagnosis and Radiotherapy in Oncology: 2nd Edition)
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