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BackgroundThe present multicenter retrospective study on eltrombopag administration in Italian children with chronic ITP aims to extend follow-up of our previous study.Materials and methodsThis retrospective multicenter study was conducted in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). Patients were classified into three subgroups: group 1 included patients who discontinued treatment due to a stable platelet count; group 2 included patients who discontinued treatment due to ineffectiveness; group 3 included patients who did not permanently discontinue treatment.Results56 patients were eligible for analysis. The median duration of eltrombopag treatment was 40 months (7–71 months). Twenty patients (36%) discontinued permanently eltrombopag. The reasons of permanent discontinuation were adverse effects (n = 1), inefficacy (n = 10), stable platelet count (n = 9). All patients of group 1 maintained a durable response without additional treatments after eltrombopag discontinuation. We found that patients of group 2 were on treatment for less time (median treatment time: 13.5 months, min: 6.0 – max: 56.0) than patients of group 1 (median treatment time: 34 months, min: 16.0 – max: 62.0) (p

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte homeostasis classically due to mutation of FAS, FASL, and CASP10 genes (ALPS-FAS/CASP10). Despite recent progress, about one-third of ALPS patients does not carry classical mutations and still remains gene orphan (ALPS-U, undetermined genetic defects). The aims of the present study were to compare the clinical and immunological features of ALPS-FAS/CASP10 versus those of ALPS-U affected subjects and to deepen the genetic characteristics of this latter group. Demographical, anamnestic, biochemical data were retrieved from medical record of 46 ALPS subjects. An enlarged panel of genes (next-generation sequencing) was applied to the ALPS-U group. ALPS-U subjects showed a more complex phenotype if compared to ALPS-FAS/CASP10 group, characterized by multiorgan involvement (P = 0.001) and positivity of autoimmune markers (P = 0.02). Multilineage cytopenia was present in both groups without differences with the exception of lymphocytopenia and autoimmune neutropenia that were more frequent in ALPS-U than in the ALPS-FAS/CASP10 group (P = 0.01 and P = 0.04). First- and second-line treatments were able to control the symptoms in 100% of the ALPS-FAS/CASP10 patients, while 63% of ALPS-U needed >2 lines of treatment and remission in some cases was obtained only after target therapy. In the ALPS-U group, we found in 14 of 28 (50%) patients 19 variants; of these, 4 of 19 (21%) were known as pathogenic and 8 of 19 (42%) as likely pathogenic. A characteristic flow cytometry panel including CD3CD4-CD8-+TCRαβ+, CD3+CD25+/CD3HLADR+, TCR αβ+ B220+, and CD19+CD27+ identified the ALPS-FAS/CASP10 group. ALPS-U seems to represent a distinct entity from ALPS-FAS/CASP10; this is relevant for management and tailored treatments whenever available.

In thelast few decades, the roles of cardio-oncology and cardiovascular geneticsgained more and more attention in research and daily clinical practice, shaping a new clinical approach and management of patients affected by cancer and cardiovascular disease. Genetic characterization of patients undergoing cancer treatment can support a better cardiovascular risk stratification beyond the typical risk factors, suchas contractile function and QT interval duration, uncovering a possible patient’s concealed predisposition to heart failure, life threatening arrhythmias and sudden death. Specifically, an integrated cardiogenetic approach in daily oncological clinical practice can ensure the best patient-centered healthcare model, suggesting, also the adequate cardiac monitoring timing and alternative cancer treatments, reducing drug-related complications. We report the case of a 14-month-old girl affected by neuroblastoma, treated by cisplatin, complicated by cardiac arrest. We described the genetic characterization of a Ryanodine receptor 2 (RYR2) gene mutation and subsequent pharmacogenomic approach to better shape the cancer treatment.

AbstractBackgroundInherited thrombocytopenias (ITs) are rare congenital bleeding disorders characterized by different clinical expression and variable prognosis. ITs are poorly known by clinicians and often misdiagnosed with most common forms of thrombocytopenia.Material and methods“CHildren with Inherited Platelet disorders Surveillance” study (CHIPS) is a retrospective – prospective observational cohort study conducted between January 2003 and January 2022 in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). The primary objective of this study was to collect clinical and laboratory data on Italian pediatric patients with inherited thrombocytopenias. Secondary objectives were to calculate prevalence of ITs in Italian pediatric population and to assess frequency and genotype–phenotype correlation of different types of mutations in our study cohort.ResultsA total of 139 children, with ITs (82 male - 57 female) were enrolled. ITs prevalence in Italy ranged from 0.7 per 100,000 children during 2010 to 2 per 100,000 children during 2022. The median time between the onset of thrombocytopenia and the diagnosis of ITs was 1 years (range 0 - 18 years). A family history of thrombocytopenia has been reported in 90 patients (65%). Among 139 children with ITs, in 73 (53%) children almost one defective gene has been identified. In 61 patients a pathogenic mutation has been identified. Among them, 2 patients also carry a variant of uncertain significance (VUS), and 4 others harbour 2 VUS variants. VUS variants were identified in further 8 patients (6%), 4 of which carry more than one variant VUS. Three patients (2%) had a likely pathogenic variant while in 1 patient (1%) a variant was identified that was initially given an uncertain significance but was later classified as benign. In addition, in 17 patients the genetic diagnosis is not available, but their family history and clinical/laboratory features strongly suggest the presence of a specific genetic cause. In 49 children (35%) no genetic defect were identified. In ninetyseven patients (70%), thrombocytopenia was not associated with other clinically apparent disorders. However, 42 children (30%) had one or more additional clinical alterations.ConclusionOur study provides a descriptive collection of ITs in the pediatric Italian population.

Objective: The association between celiac disease (CD) and immune thrombocytopenia (ITP) is still uncertain. The aim of this study was to characterize the coexistence of these two diseases in Italian children. Materials and Methods: This is a retrospective multicenter study investigating the occurrence of CD in 28 children with ITP diagnosed from January 1, 2000, to December 31, 2019. Results: The first diagnosis was ITP in 57.1% and CD in 32.1% of patients. In 3 patients (10.7%), the two diagnoses were simultaneous. All the potential and silent cases of CD in our cohort were diagnosed in the groups of 'ITP first' and 'simultaneous diagnosis'. In all children ITP was mild, and in 2 out of 8 not recovered from ITP at the time of CD diagnosis a normalization of platelet counts (>100,000/μL) occurred 3 and 5 months after starting a gluten-free diet, respectively. Conclusion: We think that screening for CD should be considered in children with ITP regardless of the presence of gastrointestinal symptoms. Furthermore, some patients may recover from ITP after starting a gluten-free diet.

Abstract Friedreich's ataxia is a rare degenerative neuromuscular disorder, caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene, with a broad clinical phenotype characterized by progressive gait and limb ataxia, dysarthria, and loss of lower limb reflexes; cardiac involvement is represented by hypertrophic cardiomyopathy, ventricular arrhythmias, and sudden cardiac deaths. Currently, no definite therapy is available, while many drugs are under investigation; for this reasons, we need markers of short‐ and long‐term treatment efficacy acting on different tissue for trial evaluation. We describe the case of a 21‐year‐old patient affected by Friedreich's ataxia on wheel‐chair, with initial cardiac involvement and electrocardiographic features characterized by thiamine treatment‐related negative T wave and QTc variations. We discuss plausible physiopathology and potential ECG role implications as an intermediate marker of treatment response in future clinical trials considering patients affected by Friedreich's ataxia.

Abstract Purpose The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a crosssectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results The age of the patients on their first clinic visit ranged from65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes (n = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the bodymass index (BMI) found decreases inBMIwith increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n = 70) were between 65 and 69 years of age, 8.97% (n = 7) were between 70 and 74 years of age, and only 1.28% (n = 1) of those were aged older than 75 years. Conclusions Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women.

OBJECTIVE: The aims of this study were to evaluate the anteroposterior displacement behavior of the center of pressure without any visual reference and determine its relationship with knee muscle strength and reports of falls in postmenopausal women. Among those with osteoporosis, the specific objective was to evaluate the correlation of thoracic kyphosis and vitamin D with center of pressure displacement. METHODS: This was a cross-sectional observational study without intervention. The assessments were performed on 126 postmenopausal women (aged 55-65 years) who were grouped according to their lumbar bone density into osteoporosis and control groups. Center of pressure was evaluated on a force platform (100 Hz frequency and 10 Hz filter), with the subjects standing on both feet with eyes closed for 60 seconds. Knee muscle strength was evaluated using an isokinetic dynamometer in concentric/concentric mode at a velocity of 60°/s. In the osteoporosis group, vitamin D was assayed, and the thoracic spine was radiographed. RESULTS: In the control group, there was a correlation between the center of pressure and knee strength (r = 0.37; p

ABSTRACT Objective: The objective of this study was to evaluate the sexual behavior of women with polycystic ovary syndrome and the relationship between sexual behavior and the clinical parameters related to this syndrome (obesity, hirsutism and menstrual irregularities). Methods: A cross-sectional study was carried out involving 48 women with polycystic ovary syndrome. The evaluation was based on the complaints reported by the women with particular emphasis on sexual satisfaction, the presence of a sexual partner, phases of the sexual response cycle (desire, arousal, orgasm and resolution phases), sexual frequency, practice of masturbation, evaluation of less usual sexual habits, degree of intimacy and the quality of communication in the women's involvement with their sexual partner. The variables of sexual behavior (sexual satisfaction, masturbation, sexual fantasies, frequency of desire, arousal and orgasm) were compared with three clinical parameters: menstrual cycle, hirsutism and body mass index (BMI). Results: The sexual initiation, ways of expressing sexuality, communication and intimacy with partner and sexual satisfaction were not influenced by the clinical aspects of the syndrome. With respect to association of polycystic ovary syndrome clinical parameters with sexual behavior, a statistically significant correlation was found with the menstrual cycle. Conclusion: The absence of menstruation affected sexual interest in activities not involving the partner, thus increasing the frequency of masturbation.

Objective: To evaluate the clinical effects of estrogen-progestin therapy in postmenopausal women, with particular emphasis on climacteric symptoms and sexuality. Methods: A prospective, blind, randomized, single-center, crossover, placebo-controlled study was carried out for 12 consecutive months in 40 postmenopausal women with a mean age of 52.2 years, with no contraindication to hormone therapy and with an intact uterus. The patients were divided into two groups: during the first six-month period of the study, one group received estradiol valerate 2 mg/day for 21 days/month associated with cyproterone acetate 1 mg/day in the last ten days of therapy (Climene™); the other group received one placebo tablet/day for 21 days/month. The treatments were then reversed, and the patients were followed-up for another six-month period. In the statistical analysis, the group receiving hormone therapy was denoted Group A, and the group receiving placebo Group B, regardless of the sequence in which the patient received the drug. Menopausal symptoms and sexuality were evaluated. Crossover analysis of variance and the McNemar test were used for statistical analysis. Rresults: A significant reduction was found in hot flashes and insomnia in the patients of Group A (the group that received hormone therapy). In this group, a significant improvement was also detected regarding sexual interest, communication with partner and ability to reach orgasm during penetration. Regarding the other issues, no statistically significant differences were detected. Cconclusions: There was a significant improvement in menopausal symptoms and sexuality in the group of women that used hormone therapy.

OBJETIVO: examinar a função lútea em adolescentes com ciclos menstruais regulares. MÉTODOS: foram incluídas neste estudo, de coorte prospectivo, 55 adolescentes eumenorrêicas, com idade entre 14 e 19 anos e menarca aos 12,2 anos. Examinaram-se o dia da ocorrência de ovulação, o grau de vascularização do corpo lúteo e o índice de resistência dos vasos ovarianos, as concentrações de progesterona e a resposta do endométrio. A ovulação foi identificada por ultra-sonografia transvaginal a partir do 2º ou 5º dia do ciclo, repetindo-a a cada dois dias. A vascularização e o índice de resistência lútea foram aferidos por dopplervelocimetria no 10º dia pós-ovulação. Os níveis de progesterona sérica foram estimados por quimioluminescência nos dias 6, 9 e 12 da fase lútea. A histologia endometrial foi analisada após biópsia feita entre o 8º e o 10º dia pós-ovulação. Usou-se software SPSS para análise estatística, assumindo-se significância quando pPURPOSE: to evaluate the luteal function in adolescents with regular menstrual cycles. METHODS: this prospective cohort study included 55 adolescents, aged 14-19 years, with menarche at 12.2 years. Ovulation was identified by ultrasound, starting on the second or fifth day of the cycle. The corpus luteum vascularization and the resistence index of the ovarian vessels were measured by Doppler on the tenth postovulatory day. Progesterone was measured by chemoluminescence on days 6, 9 and 12 of the luteal phase. The endometrial biopsy was performed 8 to 10 days after ovulation. The results were analyzed using the SPSS software and were considered significant when p

Objectives: To evaluate the frequency of obesity in postmenopausal women and assess the potential effects of increased body mass index (BMI) on lipoprotein profile and on risk factors for arterial hypertension and diabetes. Design: A cross-sectional study was conducted with 5027 postmenopausal Brazilian women. Analyses were performed of BMI and cardiovascular factors (systemic blood pressure [BP], total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL-C], triglyceride, and fast glucose). The statistical analysis included the chi-square and Mann-Whitney tests. The significance level was set at 5%. Results: Obesity (BMI >30) in our study characterized approximately 30% of the 5027 postmenopausal women. The comparison of patients with normal BMI and those with high BMI showed that high BMI had a significant negative effect on BP, as evidenced by the increased frequency of hypertension in overweight and obese patients (>25) ( p < 0.001), that it also negatively and significantly affected triglyceride ( p < 0.001) and fast glucose levels ( p < 0.001), and that it was linked significantly to low levels of HDL-C. Conclusion: Our data showed the high frequency of obesity in our population and of the cardiovascular risks (glucose, systemic arterial hypertension, and low HDL-C) associated with high BMI. [ABSTRACT FROM AUTHOR]

The association of genetic polymorphism in the estrogen receptor alpha (ERα) gene and risk for diseases including breast cancer (BC) has been the subject of great interest. Objective: Checking on women with high breast density after menopause, the frequency of the Pvull and Xbal polymorphisms of the ERα gene and the correlation between them and the known risk factors for breast cancer. Method: Observational study with 308 women between 45 and 65 years old with high breast density, without hormonal therapy, menstruation for a year or more, breast and ovarian cancer history. It was characterized in clinical history and physical examination: menarche, menopause, parity, family history of BC, smoking, alcohol intake and body mass index. Results: The allelic and genotypic frequencies for ERα- Pvull and Xbal: p = 43.99%; p = 56.01%; pp = 32.14%; Pp = 47.73% and PP = 20.13%; X = 41.56%; x = 58.44%; xx = 33.44%; Xx = 50.00% and XX = 16.56%, respectively. The most frequent risk factors for BC: menarche before 12 years old (35.38%), nulliparity or first child after 28 years old (41.66%), family history of BC (19.16%) and overweight/obesity (62.01%). Conclusion: Allelic and genotypic distribution similar to literature. The risk factors for BC were more prevalent in women with high breast density but without significant associations with these polymorphisms. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome (PCOS). Design: Prospective, randomized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile. The duration of treatment was 6 months. Statistical analysis was done using Student's t-test. Results: Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study. The menstrual pattern improved by ~67% in both groups. There was a significant decrease in waist circumference in the lifestyle changes group (101.8 ± 3.9 and 95.1 ± 3.6, at baseline and at 6 months of treatment, respectively; p < 0.001) and in body mass index (BMI) in both groups. The predictor of menstrual pattern improvement was BMI. Conclusions: Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS. This effect was related to a decrease in BMI. [ABSTRACT FROM AUTHOR]

A double-blind study of cyclofenil plus diazepam compated to placebo was carried out in 30 post-menopausal patients at the Gynaecologic Clinic of Säo Paulo University Medical School. All patients had had amenorrhoea for at least one year before the trial. Kupperman Menopausal Index (KMI), FSH, LH, prolactin and oestradiol blood levels and vaginal smears were the data analysed. Cyclofenil 400 mg plus diazepam 10 mg po daily was the prescribed standard dose, which relieved the main symptoms of the menopausal syndrome. With the dose schedule used, neither blood hormone levels nor vaginal smears data showed any statistical difference before and after treatment. Also, no important side-effects were observed. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate gynecological cancer and metabolic screening of Brazilian women aged 65 years or older., Methods: This retrospective descriptive study was conducted by including 1,001 Brazilian patients of the gynecological geriatric outpatient office of our institution to evaluate the influence of age on gynecological cancer and metabolic screening parameters at the first clinical visit. All patients were divided into three groups: a) 65 to 69 years; b) 70 to 74 years; c) ≥ 75 years. We considered clinical, laboratorial, and image data as variables of this study. The Chi-square test was used to assess the proportion of differences among the age groups, and Kruskal-Wallis was used for quantitative variables., Results: The values of BMI and height in the group over 75 years was lower than that of the 65 to 69 years (p = 0.001). Regardless of the age group, high arterial blood pressure levels were found in 85.45% of participants. Also, many patients had glucose intolerance in the blood. The pelvic ultrasonography showed abnormal endometrial echo thickness (> 5 mm) in 6.14% of patients, but with no significant statistical difference between the age groups. A total of 4.04% of patients had ovaries with high volume values ( > 6.1 mL). Abnormal mammography (BI-RADS 3 or 4) was observed in 12.21%., Conclusions: our data suggest that a great reduction in BMI and stature is more frequent in the group over 75 years. Also, systemic arterial hypertension and carbohydrate disturbance are frequent morbidities in women over 65 years.

Purpose  The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design  This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a cross-sectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results  The age of the patients on their first clinic visit ranged from 65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes ( n  = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the body mass index (BMI) found decreases in BMI with increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n  =  70) were between 65 and 69 years of age, 8.97% ( n  = 7) were between 70 and 74 years of age, and only 1.28% ( n  = 1) of those were aged older than 75 years. Conclusions  Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Female aging is a process that involves hypoestrogenism time, the individual impact on each woman, and what we can do as experts to reduce morbidity and provide quality of life. This natural process in the female life cycle has been of concern to women after menopause. Changes in different biophysical and psychosocial aspects, and their individual experiences, have repercussions on the lives of patients seeking specialized and multidisciplinary support to reduce the harmful effects of prolonged hypoestrogenism. Overweight and obesity, inadequate living habits and the presence of multi-morbidities cause damage to the quality of life and impact the functional capacity. Behavioral prescription and hormone therapy are among the treatments given to ease symptoms and reduce morbidity. A better understanding of these factors can help identify groups that require more care after menopause.

Objective: To assess the relationship of onset of menopause and body mass on the menopausal symptoms in post-menopausal Brazilian women., Design: Observational study conducted by the selection and inclusion of 5968 Brazilian women after menopause. The following variables were analyzed in this study: time at menopause; the relationship between age at menarche and age at menopause; vasomotor symptoms compared with age at the time of menopause and the time of menopause; Kupperman menopausal index (KMI) versus total time of menopause; body mass index (BMI) compared to the time of menopause, vasomotor symptoms, and KMI total score. We used the Chi-square test, and the significance level was set at 5%., Results: The age at natural menopause ranged from 41 to 62 years (mean 48.1 ± 4.07 years). A younger age at menopause was associated with a high intensity of vasomotor symptoms. These symptoms were more intense in the first 5 years of menopause and decreased with time. The KMI total also decreased with time after menopause, with the exception of arthralgia, myalgia, and insomnia, which did not tend to improve over time. In addition, the vasomotor symptoms and total KMI were more frequent with increasing BMI., Conclusions: Our results suggested that the age of menopause and BMI may influence the intensity of vasomotor symptoms.

Objective: The aim of this study was to construct and to validate a measure of the consequences of domestic violence on women's health during climacterium., Methods: A questionnaire was administered at the Outpatient Climacterium Clinic to 124 women aged 40 to 65 years who were the victims of domestic and/or sexual violence (experimental group). They were divided into three groups: (1) those who were victims of violence exclusively during childhood/adolescence, (2) those who were victims of violence exclusively during adulthood, and (3) those who were victims of violence throughout their lives. The instrument included 34 items evaluating the beginning, frequency, and type of violence; the search for health assistance and reporting of the violence; the violence and the number of comorbidities; and violence and the Kupperman Menopausal Index. We also included a control group composed of perimenopausal and postmenopausal women who did not experience any violence (n = 120)., Results: The instrument presented a Cronbach α = 0.82, good reliability among the examiners (+0.80), and a good possibility of reproducibility. The mean age of menopause was 45.4 years, and the mean age in the control group was 48.1 years. Group 1 showed a mean of 5.1 comorbidities, Group 2 had 4.6, and Group 3 had 4.4. Sexual violence (43.5%) and other types of violence both presented average comorbidities (4.60) but represented a significant impairment in the victim's sexual life. There were significant associations in group 3 and a high Kupperman Menopausal Index score. In the experimental group, 80.6% did not seek health services for the violence they experienced., Conclusions: The questionnaire presented good internal consistency and a validated construction. It can be easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual violence on women's health during climacterium.