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OBJECTIVE: Urinary tract infections still represent a significant bother for women and result in high costs to the health system. D-mannose is a simple sugar; it seems able to hinder bacteria adhesion to the urothelium. The present study aimed to determine whether Dmannose alone is effective in treating acute urinary tract infections in women and its possible utility in the management of recurrences. PATIENTS AND METHODS: This is a pilot study, performed between April 2014 and July 2015 at Department of Gynaecological Obstetrics and Urologic Sciences of "Sapienza" University of Rome. A D-mannose compound was administered twice daily for 3 days and then once a day for 10 days. Changes in patients' symptoms, the therapeutic effects and changes in quality of life (QoL) were evaluated clinically and using a specifically validated questionnaire (UTISA). After described treatment, patients were randomized in receiving or not prophylaxis in the next 6 months. RESULTS: Mean UTISA scores recorded after completing the treatment, compared with baseline scores, showed a significant improvement of the majority of symptoms (p < 0.05). D-mannose seemed to have had a significant positive effect on UTIs' resolution and QoL improvement (p = 0.0001). As prophylactic agent administered for 6 months, it showed promising results (4.5% vs. 33.3% recurrences in treated and untreated patients respectively). CONCLUSIONS: The results of this study suggest that D-mannose can be an effective aid in acute cystitis management and also a successful prophylactic agent in a selected population; however, more studies will certainly be needed to confirm the results of our pilot study. [ABSTRACT FROM AUTHOR]

Human salmonellosis is a high-priority foodborne disease worldwide. The main reservoir of Salmonella is livestock, mainly swine and poultry that are infected both by generalist serovars and serovars adapted to them. The most widespread livestock-adapted serovars are attenuated in both their primary hosts and humans. We previously identified a lineage of the swine-adapted Salmonella Derby carrying mutations in Salmonella Pathogenicity Island-1(SPI-1) giving attenuation. To evaluate if SPI-1 decay is a general feature of swine-adapted serovars, we analyzed the Enterobase global population of Salmonella serovars most frequently isolated from swine. We found that deleterious mutations in SPI-1 are accumulated more in swine-adapted ( S . Derby and Salmonella Rissen) than in generalist ( Salmonella Typhimurium, I 1,4,[5],12:i:-, and Salmonella Infantis) serovars. The genomes carrying such mutations are widespread in the population of S . Derby and S . Rissen, indicating that the occurrence and fixation of deleterious mutations in SPI-1 are frequent. Similarly, also poultry-adapted Salmonella Kentucky has accumulated deleterious mutations in SPI-1, leading to over 70% of mutated genomes of this serovar compared with negligible proportions of mutated genomes in the generalist serovars from poultry. Although in vitro attenuation of S . Derby carrying mutated SPI-1 had been previously demonstrated, we showed the same phenotype for mutated S . Rissen. Considering also the known attenuation of S . Kentucky, our population-scale findings provide evidence of progressive evolution toward the attenuation of serovars adapted to the main animal reservoirs of human salmonellosis through the food chain. Intensive farming with a high density of animals could be a possible driver of this evolution.IMPORTANCEThis study shows at the global population level of Salmonella that the main attenuated serovars adapted to food-producing animals are undergoing convergent evolution toward further attenuation through the decay of SPI-1, considered critically important for the intestinal phase of Salmonella infection. The drivers of this evolution are unknown, but they could be attributed, at least in part, to the intensive farming of livestock with its high densities. On one side, our results contribute to the knowledge of the interaction between livestock populations and their host-adapted serovars of Salmonella . On the other side, the study provides scientific background for reconsidering the microbiological criteria adopted by the food safety legislation of many countries that ask for the absence of Salmonella in foods, regardless of any virulence evaluation of the detected strain. In this respect, the study provides molecular bases to investigate the virulence of different lineages within these host-adapted serovars., Competing Interests: The authors declare no conflict of interest.

Importance: This study integrated population data with in vitro assessment of virulence phenotypes to unveil that a considerable part of the global population of Salmonella Derby is evolving to enhance its host adaptation to the swine host and that this evolution is simultaneously increasing its attenuation for humans. The study shows that the fixation of deleterious mutations in SPI-1 has a role in this process. This evidence indicates that SPI-1 has a key role for S . Derby virulence in humans but not for its circulation in swine. The results show that genes generally considered essential for Salmonella pathogenesis do not play the same key role for all Salmonella serovars or lineages and/or all hosts. The study helps in understanding the molecular mechanisms underlying the ecology and host adaptation of Salmonella showing that the adaptation process can vary for different types of Salmonella and hosts., Competing Interests: The authors declare no conflict of interest.

The political choices made by the European institutions in the last twenty years show how the conviction is increasingly rooted that the management of environmental problems and, more specifically, the fight against climate change can find a valid solution in technology and eco-innovations. This is evident starting from the last two growth strategies adopted (Europe 2020 and the European Green Deal), from the long series of measures implemented to put them into practice and from the main R&I funding programs, such as Horizon Europe. In this context, the problem of justice and inclusiveness of the various initiatives implemented is attracting growing attention. In fact, if the institutional documents assume that green and smart participated projects are also fair and inclusive, a growing body of literature based on empirical studies seems to refute this assumption. Within this framework, the present work analyses first the critical literature and then the three main preparatory documents for the Horizon Europe Mission Climate-neutral and Smart Cities, which selected 100 European cities to become climate-neutral by 2030. These have been studied through the lens of environmental justice, in order to assess the European Commission's understanding of the existing and arising equity issues in the path toward climate neutrality. The research shows that, while the first two documents seemed informed by the idea that participation automatically translates into equality, the last guidelines show a deeper acknowledgement of the multidimensional nature of environmental justice. One that, beyond participation, also considers issues of distribution, rights, responsibilities and recognition. The present work should nevertheless be understood as a preparatory, analytical tool that will require the further definition and implementation of Climate City Contracts by the selected cities, in order to assess how the issue of environmental justice is effectively being considered in each specific context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Beretta and Bracchi.)

A clinical strain of Klebsiella pneumoniae typed as sequence type 307 carrying three different alleles of the flu gene encoding the Escherichia coli virulence factor antigen 43 associated with biofilm formation was detected and characterized. The flu alleles are located in the chromosome inside putative integrative conjugative elements. The strain displays the phenotypes associated with Ag43, i.e. bi-phasic colony morphology and enhanced biofilm production. Furthermore, the strain produces low amount of capsule known to affect Ag43 function. Analysis of 1431 worldwide deposited genomes revealed that 3.7% Klebsiella pneumoniae carry one or two flu alleles., (© 2023. The Author(s).)

Background: the co-production of carbapenemases and mcr -genes represents a worrisome event in the treatment of Enterobacteriaceae infections. The aim of the study was to characterize the genomic features of two clinical Enterobacter cloacae complex (ECC) isolates, co-producing VIM and MCR enzymes, in Italy., Methods: species identification and antibiotic susceptibility profiling were performed using MALDI-TOF and broth microdilution methods, respectively. Transferability of the bla VIM- and mcr - type genes was verified through conjugation experiment. Extracted DNA was sequenced using long reads sequencing technology on the Sequel I platform (PacBio)., Results: the first isolate showed clinical resistance against ertapenem yet was colistin susceptible (EUCAST 2020 breakpoints). The mcr-9.2 gene was harbored on a conjugative IncHI2 plasmid, while the bla VIM-1 determinant was harbored on a conjugative IncN plasmid. The second isolate, resistant to both carbapenems and colistin, harbored: mcr-9 gene and its two component regulatory genes for increased expression on the chromosome, mcr-4.3 on non-conjugative (yet co-transferable) ColE plasmid, and bla VIM-1 on a non-conjugative IncA plasmid., Conclusions: to our knowledge, this is the first report of co-production of VIM and MCR in ECC isolates in Italy.

Salmonella enterica variants exhibit diverse host adaptation, outcome of infection, and associated risk to food safety. Analysis of the distribution of Salmonella enterica serovar Derby (S. Derby) subtypes in human and swine identified isolates with a distinct PFGE profile that were significantly under-represented in human infections, consistent with further host adaptation to swine. Here we show that isolates with this PFGE profile form a distinct phylogenetic sub-clade within S. Derby and exhibit a profound reduction in invasion of human epithelial cells, and a relatively small reduction in swine epithelial cells. A single missense mutation in hilD, that encodes the master-regulator of the Salmonella Pathogenicity Island 1 (SPI-1), was present in the adapted lineage. The missense mutation resulted in a loss of function of HilD that accounted for reduced invasion in human epithelial cells. The relatively small impact of the mutation on interaction with swine cells was consistent with an alternative mechanism of invasion in this pathogen-host combination.

Purpose: The recurrence of multi-drug resistant (MDR) pathogens to the latest antibiotics and the limited development of new antibacterial agents have reduced the options for the treatment of severe infections. The reintroduction of old antibiotics, such as colistin, represents an effective strategy, since the latest antibiotics are over-consumed and ineffective against MDR pathogens. In 2015, Liu (Lancet Infect Dis 16:161-168, 2016) reported Escherichia coli (E. coli) isolates carrying plasmid-mediated colistin resistance gene mcr-1. The first of mcr-1 positive colistin-resistant (col-R) E. coli from a human blood culture was observed in 2012 in Latin America, while in Italy was reported for the first time by our center in 2016. The present study aimed to describe the prevalence of mcr-1 positive col-R strains in E. coli-related bloodstream infection among patients hospitalized in Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, from 2012 to 2018, including the three cases already published., Methods: All col-R E. coli strains isolated from blood cultures collected during the study period were analyzed. The minimal inhibitory concentration of colistin was determined using broth microdilution and detection of mcr-1 and mcr-2 genes was performed by PCR. The sequence type of E. coli mcr-1 positive was determined according to Multilocus sequence typing., Results: Out of 1557 samples, 14 strains (0.90%) were col-R. and positive for the presence of the mcr-1 gene, with no mcr-2 detected. The most common ST was ST10 (n = 3), followed by ST410 (n = 2). The remaining strains exhibited different MLST profiles, indicating that they were genetically unrelated., Conclusions: Proper reporting of the presence of mcr-1 genes is an essential component to anticipate the spread of colistin resistance. This public health issue is particularly alarming in Italy due to the consistent circulation of MDR bacteria.

Objective: To evaluate the impact of age-adjusted Charlson comorbidity index (ACCI) in predicting disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) among surgically treated patients with vulvar carcinoma. The secondary aim is to evaluate its impact as a predictor of the pattern of recurrence., Methods: We retrospectively evaluated data of patients that underwent surgical treatment for vulvar cancer from 1998 to 2016. ACCI at the time of primary surgery was evaluated and patients were classified as low (ACCI 0-1), intermediate (ACCI 2-3), and high risk (>3). DFS, OS and CSS were analyzed using the Kaplan-Meir and the Cox proportional hazard models. Logistic regression model was used to assess predictors of distant and local recurrence., Results: Seventy-eight patients were included in the study. Twelve were classified as low, 36 as intermediate, and 30 as high risk according to their ACCI. Using multivariate analysis, ACCI class was an independent predictor of worse DFS (hazard ratio [HR]=3.04; 95% confidence interval [CI]=1.54-5.99; p<0.001), OS (HR=5.25; 95% CI=1.63-16.89; p=0.005) and CSS (HR=3.79; 95% CI=1.13-12.78; p=0.03). Positive nodal status (odds ratio=8.46; 95% CI=2.13-33.58; p=0.002) was the only parameter correlated with distant recurrence at logistic regression., Conclusion: ACCI could be a useful tool in predicting prognosis in surgically treated vulvar cancer patients. Prospective multicenter trials assessing the role of ACCI in vulvar cancer patients are warranted., Competing Interests: No potential conflict of interest relevant to this article was reported, (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objectives: Anogenital distance (AGD) represents the space between labia posterior commissure and anus. This was pilot study to investigate how menopause and so lack of oestrogens affects AGD., Methods: A total of 109 patients were enrolled. AGD was measured in lithotomy position using sterile paper ruler. Anogenital index (AGI) was used to control 2 variables of height and weight (body mass index, kg/m 2 ). Vaginal health index (VHI) was used to evaluate vaginal wellness. Female sexual function index (FSFI) questionnaire was administered to all women to evaluate the impact of menopause on their sexual function., Results: AGD (30.87 ± 2.98 vs. 17.57 ± 2.18; P = 0.0001) and AGI (1.40 ± 0.21 vs. 0.70 ± 0.15; P = 0.0001) were both significantly lower in the postmenopausal group. Postmenopausal women were affected by vulvovaginal atrophy (VVA) significantly. Thus, VHI scores were dramatically worse in postmenopausal group (23.95 ± 1.28 vs. 10.75 ± 3.41; P = 0.0001) as well as FSFI results (32.68 ± 2.25 vs. 19.78 ± 5.46; P = 0.0001)., Conclusions: This study confirms that AGD in post-menopausal women was significantly shorter than AGD in premenopausal women, correlating with an increase of VVA and sexual impairment. Changes of AGD and AGI demonstrated to predict hormonal changes that may occur after menopause., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Background: Vulvar cancer is a rare disease accounting for approximately 5% of female genital tract tumors worldwide. Currently surgery represents the mainstay alone or sometimes, in combination with chemo-radiotherapy, for locally advanced tumors and recurrent disease. However, significant physical and sexual impairment mostly due to anatomical distortion of external genitalia are a consequence of radical surgical treatment. Postoperative reconstruction after demolitive surgeries improves aesthetic and functional results, guarantees an adequate coverage of large tumors and assures safe surgical margin. The present study aimed to analyze feasibility and complication rates of fascio-cutaneous flap after excision for vulvovaginal malignancies., Methods: PubMed (MEDLINE), Web of Science, and CINAHL were searched for records of validated vulvovaginal reconstructive techniques after demolitive surgery for vulvar cancer. All cohorts were rated for quality using a scoring method taking into account the design of the study, the sample size and quality of report of surgical data and complications., Results: A total of 24 studies met all eligibility criteria for this systematic review. All the studies were realized between 1996 and 2015. The overall sample size was 443 patients. Two major group of flap according to type of movement were identified: Advancement Flap (V-Y Gluteal Fold Flap; Medial Thigh Flap) and Transpositional Flap (Lotus Petal Flap; Gluteal Thigh Flap; Gluteal Fold Flap and Anterolateral Thigh Flap). The overall complications rates reported for advancement (26.7% among 165 patients on 11 series) and transposition flaps (22.3% among 278 patients on 13 series) were comparable., Conclusions: A tailored procedure, based on patients' characteristics, size and location of the defect is still the goal of a successful reconstructive surgery. Proper planning of the surgical procedures, knowledge of the different surgical options and technical skills are required in order to obtain reliable and satisfying results., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Ovarian cancer is a most lethal gynecologic tumor. The mainstay treatment is cytoreductive surgery followed by platinum-based chemotherapy. However, a high percentage of patients recur, thus needing multiple treatments with a frequently poor prognosis. In the last two decades, research has focused on the potential of target therapies to improve the survival of patients affected by ovarian cancer. Bevacizumab is one of the most studied target therapies, and it is approved for first- and second-line treatment of advanced epithelial ovarian, fallopian tube, and primary peritoneal tumors. Despite its widespread use with favorable results, controversy regarding patient selection and the best schedule, dosage, and timing of bevacizumab still exists. This review summarizes the state of the art on the use of bevacizumab for ovarian cancer in front-line, recurrence, and neoadjuvant settings. This study focuses on the results of pivotal trials, emerging data, ongoing research, and still unanswered questions about the most adequate dosage of bevacizumab and its potential activity after disease progression or rechallenge in previously treated patients., (© 2016 S. Karger AG, Basel.)

Vulvodynia is a women's health problem that may affect as many as 15% of women who seek gynecological care, and yet little attention is given to this condition and it is frequently dismissed as psychosomatic. Thus, vulvodynia still remains a major health problem in Western countries, leading to significant morbidity and a reduced quality of life for many women. This condition carries large costs incurred as a result of both medical treatment and lost productivity. Vulvodynia is becoming a universal priority in the prevention, care, education, and research areas of pain and its consequences and it remains one of the poorly understood complex chronic pain syndromes, representing a multifactorial clinical syndrome of unexplained vulvar pain and sexual dysfunction.

Despite the dramatic improvements achieved in cancer treatment through a better understanding of the tumor biology, ovarian cancer is still characterized by a poor prognosis: most patients diagnosed with this disease will ultimately die from it. In various clinical trials conducted over a time span of two decades, new combinations of conventional chemotherapy regimens have failed to achieve significant improvements in oncologic outcome in ovarian cancer patients. We have now entered an era of "personalized medicine" in which new medications are designed to specifically target molecular pathways involved in carcinogenesis and cancer progression. Encouraging results in different tumor types have been reported, applying an increasing number of target therapies that are still under evaluation. In this setting, one of the most successfully targeted molecular pathways is tumor angiogenesis. Bevacizumab, a monoclonal antibody binding vascular endothelial growth factor (VEGF), has been recently incorporated in the treatment of primary and recurrent ovarian cancer patients after multiple phase III randomized controlled trials have proven its clinical benefit. Based on these positive results, more anti-angiogenic molecules using different mechanisms of action have been developed and are currently under investigation. Among these molecules, the tyrosine kinases inhibitors are probably the most promising ones. Cediranib is a tyrosine kinase inhibitor targeting VEGF receptors that has been tested in various trials with promising results. The aim of this manuscript is to review the current role of cediranib in the treatment of ovarian cancer and to present an overview of the ongoing clinical trials in this setting.

Introduction: This is the first case of suture granuloma mimicking isolated ovarian cancer relapse. Only six analogous cases have been previously reported in other malignancies., Case Presentation: We report the case of a 44-year-old Caucasian woman with partially platinum-sensitive ovarian cancer in which radiological features, including computed tomography and combined 18F-fluorodeoxyglucose-positron emission tomography/computed tomography, were strongly suggestive of isolated cancer relapse in her right subdiaphragmatic region. Laparoscopic examination resulted negative, but was not completely suitable due to widespread adhesive syndrome. The laparotomy for secondary cytoreductive surgery and biopsy of the suspected area showed inflammatory granuloma caused by nonabsorbable propylene suture, without evidence of neoplastic cells. Moreover, unexpected peritoneal carcinosis was found., Conclusions: This evidence suggests that clinical details about previous surgical procedures are necessary for adequate interpretation. Although much progress has been made in imaging techniques, especially in the promising field of combined 18F-fluorodeoxyglucose positron emission tomography/computed tomography, these procedures should be still thoroughly investigated in order to promptly rule out tumor recurrence and avoid unnecessary surgery.

Objective: The aim of the study is to assess the feasibility and complications of the modified V-Y advancement gluteal flap in the vulvo-perineal reconstruction among women operated for vulvar malignancies., Methods: From December 2008 to April 2012 women who underwent radical surgery for invasive vulvar cancer were considered for the study. Patients after demolitive procedure were submitted to reconstructive step (Group A) consisting of bilateral or monolateral V-Y advancement fascio-cutaneous flap, from gluteal fold. Surgical results were compared to those of a historical group of patients (Group B) with the same characteristics but not submitted to the reconstructive step., Results: Twenty-nine patients were considered for the study and submitted to radical surgery followed by V-Y flap. Surgical results were compared to those of 78 patients submitted to demolitive surgery only. There were no differences in terms of clinical characteristics between the two groups. The average length of hospital stay was 7 and 10 days, respectively for Groups A and B (P=0.0067). Mean operating time was higher in Group A, 210 vs 120 min (P<0.00001). Among women with tumor size larger than 4 cm (27 Group A, 30 Group B), Group A had lower complication rate (dehiscence 11% vs 40%; P=0.0172)., Conclusions: Modified gluteal fold advancement V-Y flap is a safe and simple procedure and can be harvested in a single surgery session. It could be able to reduce hospital stay and in patients with large loss of substance could reduce rate of complications., (Copyright © 2013 Elsevier Inc. All rights reserved.)