This extensive review summarizes clinical evidence on immunotherapy and targeted therapy currently available for endometrial cancer (EC) and reports the results of the clinical trials and ongoing ...studies. The research was carried out collecting preclinical and clinical findings using keywords such as immune environment, tumor infiltrating lymphocytes, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, immune checkpoint inhibitors, anti-PD-1/PD-L1 antibodies and others' on PubMed. Finally, we looked for the ongoing immunotherapy trials on ClinicalTrials.gov. EC is the fourth most common malignancy in women in developed countries. Despite medical and surgical treatments, survival has not improved in the last decade and death rates have increased for uterine cancer in women. Therefore, identification of clinically significant prognostic risk factors and formulation of new rational therapeutic regimens have great significance for enhancing the survival rate and improving the outcome in patients with advanced or metastatic disease. The identification of genetic alterations, including somatic mutations and microsatellite instability, and the definition of intracellular signaling pathways alterations that have a major role in in tumorigenesis is leading to the development of new therapeutic options for immunotherapy and targeted therapy.
To report cases of use of chelation therapy during pregnancy which resulted in favorable outcomes for the babies.
In this retrospective cohort study, we described the evolution and outcome of 9 ...pregnancies in Italian thalassemic women who received deferoxamine (DFO) inadvertently during early pregnancy.
The use of deferoxamine during first trimester did not lead to adverse effects on the fetus or cause major complications for the gestation, although an increase in iron burden was observed after suspending chelation therapy.
In our experience, iron-chelation therapy might be administrated in pregnancy where the benefits to the mother outweigh the potential risks to the baby.
Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we ...analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.
This prospective observational study aimed to assess the association between maternal abdominal subcutaneous and visceral fat thickness measured with ultrasound scan during the first trimester and ...the risk of developing gestational diabetes mellitus (GDM).
We recruited 43 non-diabetic women with singleton pregnancy between 11 and 14 week of gestation and evaluated ultrasonographic measurements of subcutaneous fat thickness (SFT) and preperitoneal fat (PF) above the umbilicus. During the 2
trimester, GDM screening was performed by 75 g two-hour oral glucose tolerance test (OGTT) and diagnosis was made when one or more plasma glucose values meets or exceeds the values indicated by International Association of the Diabetes and Pregnancy Study Groups (IADPSG).
Among the 43 woman, 8 developed GDM (18.6%). Of these 37,5% (N.=3) had been diagnosed with GDM during a previous pregnancy, with a statistically significant correlation (P=0.035). Mean SFT for all patients was significantly higher in the GDM group compared to non-GDM group (27.30±8.78 mm vs. 18.56±9.99 mm; P=0.049). Mean PF for all women showed a statistically significant correlation with GDM (13.27±9.07 mm for non GDM group vs. 23.52±10.24 mm for GDM group; P=0.038).
Abdominal adiposity, both subcutaneous and visceral, seem to be a suitable predictor of GDM in early pregnancy and it can be easily assessed during a first trimester routine ultrasound, although further studies are needed to evaluate their role in the screening protocols.
The aim of this study was to assess the effectiveness of ospemifene in the improvement of sexual function in postmenopausal women with vulvovaginal atrophy (VVA) affected by overactive bladder ...syndrome (OAB) or urge urinary incontinence (UUI). One hundred five postmenopausal patients with VVA affected by OAB and/or UUI were enrolled for the study. All patients received ospemifene 60 mg for 12 weeks. Clinical examination, 3-d voiding diary and the vaginal health index (VHI) were performed at baseline and at 12 weeks. Patients completed the OAB-Q SF, FSFI, FSDS, and SF-36 questionnaires. The patient's satisfaction was also calculated. After 12 weeks, the reduction of urinary symptoms was observed. The OAB-Q symptoms, OAB-Q (HRQL) score were (55.34 ± 13.54 vs. 23.22 ± 9.76; p < .0001) and (22.45 ± 9.78 vs. 70.56 ± 15.49; p < .0001), before and after treatment. SF-36 questionnaire showed a significant improvement (p < .0001). VHI score increased and the women who regularly practice sexual activity increased after treatment. The total FSFI score increased significantly and the FSDS score changed after 12 weeks (p < .0001). The PGI-I after 12 weeks showed a total success rate of 90.5%. Ospemifene is an effective potential therapy for postmenopausal women with VVA affected by OAB or UUI improving sexual function and quality of life.
Malaria in pregnancy is an important cause of maternal and foetal morbidity and is a potentially life-threatening infection. With ever-growing global exchanges, imported malaria in pregnancy is ...becoming an issue of concern in non-endemic countries where women, because of low immunity, have higher risk of severe diseases and death. Malaria in pregnancy is a dangerous condition which can be associated with important consequences for both mother and child such as stillbirth, low birth weight, maternal anaemia. In non-endemic-countries it is more frequent in its severe form which can lead to maternal death if not treated adequately. Specific anti-malarial interventions such as the use of repellents and insecticide treated bed nets in addition to chemoprophylaxis should be used by pregnant women if they are travelling to endemic areas. In cases of confirmed infection, specific treatment regimens vary according to gestational age and the presence of complications. Malaria should be considered a global health problem, increasingly involving western countries. Clinicians all over the world need to be prepared for this emerging disease both in terms of prevention and therapy.
This extensive review summarizes clinical evidence on immunotherapy and targeted therapy currently available for endometrial cancer (EC) and reports the results of the clinical trials and ongoing ...studies. The research was carried out collecting preclinical and clinical findings using keywords such as immune environment, tumor infiltrating lymphocytes, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression, immune checkpoint inhibitors, anti-PD-1/PD-L1 antibodies and others' on PubMed. Finally, we looked for the ongoing immunotherapy trials on ClinicalTrials.gov. EC is the fourth most common malignancy in women in developed countries. Despite medical and surgical treatments, survival has not improved in the last decade and death rates have increased for uterine cancer in women. Therefore, identification of clinically significant prognostic risk factors and formulation of new rational therapeutic regimens have great significance for enhancing the survival rate and improving the outcome in patients with advanced or metastatic disease. The identification of genetic alterations, including somatic mutations and microsatellite instability, and the definition of intracellular signaling pathways alterations that have a major role in in tumorigenesis is leading to the development of new therapeutic options for immunotherapy and targeted therapy.
Dyspareunia, especially in reproductive age, often has a negative impact on women’s sexual life, with great psychological impact. Our aim was to assess the effect of a device containing verbascoside, ...glycerophosphoinositol (GPI), hyaluronic acid sodium salt (HANa) and carrageenan (CG) for the treatment of idiopathic dyspareunia and its impact on sexual function in reproductive age women.
We recruited 43 sexually active women of reproductive age who had been suffering from superficial idiopathic dyspareunia in the last 6 months. The therapy with a device containing verbascoside, GPI, HANa and CG was applied in the vulvar and vaginal area twice a day for 12 weeks. Quality of Life (QoL) and the sexual function were assessed with Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) questionnaires before and after 12 weeks of treatment.
After treatment, the mean FSFI total score was 27.87 ± 1.86, significantly higher than before treatment (p < 0.0001). Improvement in distress about sex life was shown after treatment. The mean FSDS total score decreased significantly after 12 weeks (p < 0.0001). A reduction in dyspareunia measured with a VAS scale was observed.
Local application of a combination of verbascoside, GPI, HANa and CG effectively reduced dyspareunia and pain without any important adverse effects.
Introduction
Immunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event ...(irAE) diagnosed in 15% of patients and associated with a positive clinical response. Therefore, a detailed characterization of immune cells during vitiligo onset in melanoma patients would give insight into the immune mechanisms mediating both the irAE and the anti-tumor response.
Methods
To better understand these aspects, we analyzed T cell subsets from peripheral blood of metastatic melanoma patients undergoing treatment with anti-programmed cell death protein (PD)-1 antibodies. To deeply characterize the antitumoral T cell response concomitant to vitiligo onset, we analyzed T cell content in skin biopsies collected from melanoma patients who developed vitiligo. Moreover, to further characterize T cells in vitiligo skin lesion of melanoma patients, we sequenced T cell receptor (TCR) of cells derived from biopsies of vitiligo and primary melanoma of the same patient.
Results and discussion
Stratification of patients for developing or not developing vitiligo during anti-PD-1 therapy revealed an association between blood reduction of CD8-mucosal associated invariant T (MAIT), T helper (h) 17, natural killer (NK) CD56
bright
, and T regulatory (T-reg) cells and vitiligo onset. Consistently with the observed blood reduction of Th17 cells in melanoma patients developing vitiligo during immunotherapy, we found high amount of IL-17A expressing cells in the vitiligo skin biopsy, suggesting a possible migration of Th17 cells from the blood into the autoimmune lesion. Interestingly, except for a few cases, we found different TCR sequences between vitiligo and primary melanoma lesions. In contrast, shared TCR sequences were identified between vitiligo and metastatic tissues of the same patient. These data indicate that T cell response against normal melanocytes, which is involved in vitiligo onset, is not typically mediated by reactivation of specific T cell clones infiltrating primary melanoma but may be elicited by T cell clones targeting metastatic tissues. Altogether, our data indicate that anti-PD-1 therapy induces a de novo immune response, stimulated by the presence of metastatic cells, and composed of different T cell subtypes, which may trigger the development of vitiligo and the response against metastatic tumor.
Based on the job demands-resources (JD-R) model, the present study aimed to validate "The Technical and Administrative Staff Quality of Life At Work" (TASQ@work), a new tool to assess the quality of ...life at work in academia focused on technical and administrative staff.
This tool was developed by the QoL@Work research team, a group of expert academics in the field of work and organizational psychology affiliated with the Italian Association of Psychologists. The TASQ@work was elaborated in different steps. The first phase was aimed at the identification of the dimensions of the tool. The second phase was aimed to assess the psychometric properties of the tool. The validation process involved confirmatory analysis and measurement invariance of the various constructs selected. The analyses were performed in a convenience sample of two Italian universities in different regions (one in the Northwest and the second in Central Italy).
The sample was composed of 1820 Administrative Staff, comprising 69.4% from University 1 (
= 1,263) and 30.6% from University 2 (
= 557). The TASQ@work presented satisfactory psychometric properties (normality of the items, reliability and content, construct and nomological validity) and measurement invariance across gender, seniority, and Athenaeum.
The results indicate that the tool can be considered a reliable and valid instrument to assess job demands, job resources, and outcomes in the working life of technical and administrative academic staff. In this perspective, the present study represents the first contribution to the debate on the psychosocial risks in academic contexts by presenting a new tool, the TASQ@work, aimed at contextualizing the JD-R model to understand the role played by psychosocial aspects in affecting the well-being of the academic employees.