Efficacy of topical minoxidil in enhancing beard growth in a group of transgender assigned female at birth individuals on gender affirming hormone therapy.

PURPOSE: Testosterone therapy represents the cornerstone of gender affirming hormone therapy (GAHT) among t-AFAB (transgender Assigned Female At Birth) people. Minoxidil is a vasodilator drug approved for topical use for the treatment of androgenetic alopecia. The aim of the present study was to evaluate the efficacy of topical minoxidil in enhancing beard growth in a group of t-AFAB people on GAHT. METHODS: Sixteen t-AFAB individuals with an incomplete beard development, on GAHT for at least 6 months, were enrolled. Topical minoxidil was applied to the interested facial areas. Before starting (T0), after 3 (T3) and 6 (T6) months, we evaluated facial hair growth using the Ferriman-Gallwey modified score (FGm). RESULTS: Subjects were 26 (2.7) years old and on GAHT for 18.5 [15-54] months; using a paired match evaluation, a statistically significant facial hair growth was observed over time, in particular at T6 (median upper lip FGm 3.5 [3-4] vs 2 [1-2] at T0 and chin FGm 4 [3.25-4] vs 1 [1-2] at T0; p ≤ 0.002). Comparing the minoxidil group with a control group (n = 16) matched for age and BMI who developed a full-grown beard only with GAHT, a logistic multivariable analysis identified hirsutism before GAHT was independently positively associated with the development of a full beard [OR 15.22 (95% CI 1.46-158.82); p = 0.023]. CONCLUSIONS: This is the first study demonstrating the efficacy of topical minoxidil in enhancing facial hair growth among t-AFAB people on GAHT. Further studies will be necessary to assess whether the obtained improvements will persist after discontinuing the medication.

Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer.

BACKGROUND: ESR1 mutations have been identified as mechanism for endocrine resistance and are also associated with a decreased overall survival. We assessed ESR1 mutations in circulating tumor DNA (ctDNA) for impact on outcome to taxane-based chemotherapy in advanced breast cancer patients. METHODS: ESR1 mutations were determined in archived plasma samples from patients treated with paclitaxel and bevacizumab (AT arm, N = 91) in the randomized phase II ATX study. Samples collected at baseline (n = 51) and at cycle 2 (n = 13, C2) were analyzed using a breast cancer next-generation sequencing panel. This study was powered to detect a benefit in progression-free survival (PFS) at six months for patients treated with paclitaxel/bevacizumab compared to historical trials with fulvestrant. PFS, overall survival (OS), and ctDNA dynamics were exploratory analyses. RESULTS: PFS at six months was 86% (18/21) in patients with an ESR1 mutation detected and 85% (23/27) in wildtype ESR1 patients. In our exploratory analysis, median progression-free survival (PFS) was 8.2 months [95% CI, 7.6-8.8] for ESR1 mutant patients versus 8.7 months [95% confidence interval (CI), 8.3-9.2] for ESR1 wildtype patients [p = 0.47]. The median overall survival (OS) was 20.7 months [95% CI, 6.6-33.7] for ESR1 mutant patients versus 28.1 months [95% confidence interval (CI), 19.3-36.9] for ESR1 wildtype patients [p = 0.27]. Patients with ≥ two ESR1 mutations had a significantly worse OS, but not PFS, compared to those who did not [p = 0.003]. Change in ctDNA level at C2 was not different between ESR1 and other mutations. CONCLUSIONS: Presence of ESR1 mutations in baseline ctDNA might not be associated with inferior PFS and OS in advanced breast cancer patients treated with paclitaxel/bevacizumab.

Gender-affirming hormone treatment: friend or foe? Long-term follow-up of 755 transgender people.

PURPOSE: Gender-affirming hormone treatment (GAHT) is one of the main demands of transgender and gender diverse (TGD) people, who are usually categorised as transgender assigned-male-at birth (AMAB) and assigned-female-at birth (AFAB). The aim of the study is to investigate the long-term therapeutic management of GAHT, considering hormonal targets, treatment adjustments and GAHT safety. METHODS: A retrospective, longitudinal, observational, multicentre clinical study was carried out. Transgender people, both AMAB and AFAB, were recruited from two Endocrinology Units in Italy (Turin and Modena) between 2005 and 2022. Each subject was managed with specific and personalized follow-up depending on the clinical practice of the Centre. All clinical data routinely collected were extracted, including anthropometric and biochemical parameters, lifestyle habits, GAHT regime, and cardiovascular events. RESULTS: Three-hundred and two transgender AFAB and 453 transgender AMAB were included. Similar follow-up duration (p = 0.974) and visits' number (p = 0.384) were detected between groups. The transgender AFAB group reached therapeutic goals in less time (p = 0.002), fewer visits (p = 0.006) and fewer adjustments of GAHT scheme (p = 0.024). Accordingly, transgender AFAB showed a higher adherence to medical prescriptions compared to transgender AMAB people (p < 0.001). No significantly increased rate of cardiovascular events was detected in both groups. CONCLUSION: Our real-world clinical study shows that transgender AFAB achieve hormone target earlier and more frequently in comparison to transgender AMAB individuals. Therefore, transgender AMAB people may require more frequent check-ups in order to tailor feminizing GAHT and increase therapeutic adherence.

SIGIS-SIAMS-SIE position statement of gender affirming hormonal treatment in transgender and non-binary people.

PURPOSE: Gender Incongruence (GI) is a marked and persistent incongruence between an individual's experienced and the assigned gender at birth. In the recent years, there has been a considerable evolution and change in attitude as regards to gender nonconforming people. METHODS: According to the Italian Society of Gender, Identity and Health (SIGIS), the Italian Society of Andrology and Sexual Medicine (SIAMS) and the Italian Society of Endocrinology (SIE) rules, a team of experts on the topic has been nominated by a SIGIS-SIAMS-SIE Guideline Board on the basis of their recognized clinical and research expertise in the field, and coordinated by a senior author, has prepared this Position statement. Later on, the present manuscript has been submitted to the Journal of Endocrinological Investigation for the normal process of international peer reviewing after a first internal revision process made by the SIGIS-SIAMS-SIE Guideline Board. RESULTS: In the present document by the SIGIS-SIAMS-SIE group, we propose experts opinions concerning the psychological functioning, gender affirming hormonal treatment, safety concerns, emerging issues in transgender healthcare (sexual health, fertility issues, elderly trans people), and an Italian law overview aimed to improve gender non-conforming people care. CONCLUSION: In this Position statement, we propose experts opinions concerning the psychological functioning of transgender people, the gender-affirming hormonal treatment (full/partial masculinization in assigned female at birth trans people, full/partial feminization and de-masculinization in assigned male at birth trans people), the emerging issues in transgender health care aimed to improve patient care. We have also included an overview of Italian law about gender affirming surgery and registry rectification.

Magnesium alginate in patients with laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is a common disease caused by the leaking beck of gastric material out of the esophagus. The main symptoms are dysphonia, dysphagia, and cough. There is an established use of proton pump inhibitors (PPI) in patients with suspected LPR in common practice. This habit is translated by the standard strategy to use PPI in treating patients with gastroesophageal reflux. However, PPI can not wholly inhibit all types of reflux and are burden by adverse effects. Alginate, a derivative from algae, is devoid of side effects and effectively counteracts gastric material reflux forming a foaming gel in the stomach. The current study enrolled 100 outpatients with LPR. Alginate treatment was administered for two months. Patients underwent four visits (at baseline and 15, 30, and 60 days after treatment). A visual analog scale assessed the perception of dysphonia, dysphagia, and cough. Alginate significantly (p<0.0001) reduced all parameters. Therefore, the current study demonstrated that magnesium alginate was effective and safe in LPR treatment.

Neuroendocrine predictors of vasoplegia after cardiopulmonary bypass.

PURPOSE: Vasoplegia often complicates on-pump cardiac surgery. Systemic inflammatory response induced by extracorporeal circulation represents the major determinant, but adrenal insufficiency and postoperative vasopressin deficiency may have a role. Pathophysiological meaning of perioperative changes in endocrine markers of hydro-electrolyte balance has not still fully elucidated. Objectives of the present research study were to estimate the incidence of vasoplegia in a homogeneous cohort of not severe cardiopathic patients, to define the role of presurgical adrenal insufficiency, to evaluate copeptin and NT-proBNP trends in the perioperative. METHODS: We conducted a prospective cohort study in the cardiac intensive care unit of a tertiary referral center. We evaluated 350 consecutive patients scheduled for cardiac surgery; 55 subjects completed the study. Both standard and low-dose corticotropin stimulation tests were performed in the preoperative; copeptin and NT-proBNP were evaluated in the preoperative (T0), on day 1 (T1) and day 7 (T2) after surgery. RESULTS: Nine subjects (16.3%) developed vasoplegic syndrome with longer bypass and clamping time (p < 0.001). Reduced response to low-dose ACTH test was not associated to vasoplegia. Preoperative copeptin > 16.9 pmol/L accurately predicted the syndrome (AUC 0.86, 95% CI 0.73-0.94; OR 1.17, 95% CI 1.04-1.32). An evident correlation was observed at 7 days postoperative between NT-proBNP and copeptin (r 0.88, 95% CI 0.8-0.93; p < 0.001). CONCLUSION: Preoperative impaired response to low-dose ACTH stimulation test is not a risk factor for post-cardiotomic vasoplegia; conversely, higher preoperative copeptin predicts the complication. On-pump cardiac surgery could be an interesting model of rapid heart failure progression.

Dissection of DLBCL microenvironment provides a gene expression-based predictor of survival applicable to formalin-fixed paraffin-embedded tissue.

Background: Gene expression profiling (GEP) studies recognized a prognostic role for tumor microenvironment (TME) in diffuse large B-cell lymphoma (DLBCL), but the routinely adoption of prognostic stromal signatures remains limited. Patients and methods: Here, we applied the computational method CIBERSORT to generate a 1028-gene matrix incorporating signatures of 17 immune and stromal cytotypes. Then, we carried out a deconvolution on publicly available GEP data of 482 untreated DLBCLs to reveal associations between clinical outcomes and proportions of putative tumor-infiltrating cell types. Forty-five genes related to peculiar prognostic cytotypes were selected and their expression digitally quantified by NanoString technology on a validation set of 175 formalin-fixed, paraffin-embedded DLBCLs from two randomized trials. Data from an unsupervised clustering analysis were used to build a model of clustering assignment, whose prognostic value was also assessed on an independent cohort of 40 cases. All tissue samples consisted of pretreatment biopsies of advanced-stage DLBCLs treated by comparable R-CHOP/R-CHOP-like regimens. Results: In silico analysis demonstrated that higher proportion of myofibroblasts (MFs), dendritic cells, and CD4+ T cells correlated with better outcomes and the expression of genes in our panel is associated with a risk of overall and progression-free survival. In a multivariate Cox model, the microenvironment genes retained high prognostic performance independently of the cell-of-origin (COO), and integration of the two prognosticators (COO + TME) improved survival prediction in both validation set and independent cohort. Moreover, the major contribution of MF-related genes to the panel and Gene Set Enrichment Analysis suggested a strong influence of extracellular matrix determinants in DLBCL biology. Conclusions: Our study identified new prognostic categories of DLBCL, providing an easy-to-apply gene panel that powerfully predicts patients' survival. Moreover, owing to its relationship with specific stromal and immune components, the panel may acquire a predictive relevance in clinical trials exploring new drugs with known impact on TME.

The role of heavy metals and polychlorinated biphenyls (PCBs) in the oncogenesis of head and neck tumors and thyroid diseases: a pilot study.

Previous literature has highlighted the mechanisms of molecular toxicity induced by substances such as arsenic, cadmium, chromium, nickel, lead, barium and PCBs. The research was carried out on 20 volunteers, all the patients gave their consent to the research: the aim of the study was to evaluate the presence of metals and PCBs in these different matrices (blood and hair), correlating the biochemical data to pathological conditions present, and also to the area in which patients resided. Various quantitative determinations were carried out on samples of blood and hair for 14 heavy metals and on blood samples for 12 PCBs. For the 11 patients the results indicated that blood levels for half of the 14 displayed heavy metals measured considerably higher compared to the reference values, whilst the levels measured in hair evidenced some positive values significantly higher than the maximum reference. Of the 12 PCBs assayed in blood some showed higher positive values compared to the maximum tabular reference (although there is no clear reference quantified in the WHO-2005 report). In the 9 healthy patients heavy metals in the blood were within the expected target range, with those showing positive results (≤ 3 out of 14 heavy metals for each patient) having values only slightly higher than the reference maximum. The levels of 14 heavy metals measured in hair were below thresholds, and levels for the 12 PCBs measured in blood showed negativity or positivity with values close to the minimum benchmarks. The analyses carried out on biological matrices have uncovered important and significant differences between healthy and unhealthy subjects, both qualitative and quantitative differences with respect to heavy metals and PCBs. All patients with head and neck cancer enlisted for the study had heavy metal and PCB blood levels at least twice the maximum reference level. The levels of heavy metals in hair were at least double the maximum reference. In contrast, all healthy volunteers enrolled showed no significant levels for either metals or PCBs.

Reproducibility and validity of the Italian version of the International Physical Activity Questionnaire in obese and diabetic patients.

PURPOSE: Aims of this study were to evaluate the agreement between the short and long versions of the International Physical Activity Questionnaire (IPAQ: Italian versions), their reproducibility (agreement and reliability) and construct validity (relative to pedometry) in a clinical population. METHODS: Ninety patients affected by obesity (N = 39), type 2 diabetes mellitus (N = 26) or both (N = 25) were recruited. They were asked to maintain their usual physical activity habits during two consecutive weeks and to fill the questionnaires twice (at the end of each week). They were also asked to wear a pedometer for 7 consecutive days after the first administration of the questionnaires. RESULTS: We found acceptable agreement between the IPAQ short and long versions (ICC2,1 values were 0.81 and 0.77 for the 1st and 2nd administration), uncertain reproducibility (acceptable reliability but poor agreement) and inadequate validity relative to pedometry (the correlation coefficients between all IPAQ scores and daily steps were <0.50) for both IPAQ short and IPAQ long. CONCLUSIONS: The IPAQ use may be justified in daily clinical practice and in clinical research (e.g., in cross-sectional studies) for a simple and rapid evaluation of the physical activity level for discriminative purposes. However, the use of these questionnaires does not appear suitable for prospective interventional studies in which the level of physical activity of the recruited patients has to be assessed over time.

Treating varicocele in 2018: current knowledge and treatment options.

PURPOSE: Varicocele is defined as a state of varicosity and tortuosity of the pampiniform plexus around the testis caused by retrograde blood flow through the internal spermatic vein. The prevalence of clinically relevant varicocele ranges from 5 to 20% in the male population and is often associated with infertility and reduction of sperm quality. In this review, the pathophysiology and clinical aspects of varicocele are reviewed along with therapeutic options and treatment effects on sperm parameters and fertility both in adult and in pediatric/adolescent subjects. METHODS: We conducted a Medline and a PubMed search from 1965 to 2018 to identify publications related to varicocele clinical aspects, treatment procedures and treatment outcomes. Keywords used for the search were: "varicocele", "varicocelectomy", "sclerotherapy", "male infertility", "subfertility", and "semen abnormalities". RESULTS: Data from a large number of studies in adolescent and adult males indicate that varicocele correction improves semen parameters in the majority of patients, reducing oxidative stress and improving sperm nuclear DNA integrity either with surgical or percutaneous approach. CONCLUSIONS: Varicocele repair seems to represent a cost-effective therapeutic option for all males (both adolescent and adults) with a clinical varicocele in the presence of testicular hypotrophy, worsening sperm alterations or infertility. On the other hand, some investigators questioned the role of varicocelectomy in the era of assisted reproduction. Thus, a better understanding of the pathophysiology of varicocele-associated male subfertility is of paramount importance to elucidating the deleterious effects of varicocele on spermatogenesis and possibly formulating new treatment strategies.

Cholesteatoma vs granulation tissue: a differential diagnosis by DWI-MRI apparent diffusion coefficient.

PURPOSE: To diagnose cholesteatoma when it is not visible through tympanic perforation, imaging techniques are necessary. Recently, the combination of computed tomography and magnetic resonance imaging has proven effective to diagnose middle ear cholesteatoma. In particular, diffusion weighted images have integrated the conventional imaging for the qualitative assessment of cholesteatoma. Accordingly, the aim of this study was to obtain a quantitative analysis of cholesteatoma calculating the apparent diffusion coefficient value. So, we investigated whether it could differentiate cholesteatoma from other inflammatory tissues both in a preoperative and in a postoperative study. METHODS: This study included 109 patients with clinical suspicion of primary or residual/recurrent cholesteatoma. All patients underwent preoperative computed tomography and magnetic resonance imaging with diffusion sequences before primary or second-look surgery to calculate the apparent diffusion coefficient value. RESULTS: We found that the apparent diffusion coefficient values of cholesteatoma were significantly lower than those of non cholesteatoma. In particular, the apparent diffusion coefficient median value of the cholesteatoma group (0.84 × 10- 3 mm2/s) differed from the inflammatory granulation tissue (2.21 × 10- 3 mm2/s) group (p < 2.2 × 10- 16). Furthermore, we modeled the probability of cholesteatoma by means of a logistic regression and we determined an optimal cut-off probability value of ~ 0.86 (specificity = 1.0, sensitivity = 0.97), corresponding to an apparent diffusion coefficient cut-off value of 1.37 × 10- 3 mm2/s. CONCLUSIONS: Our study has demonstrated that apparent diffusion coefficient values constitute a valuable quantitative parameter for preoperative differentiation of cholesteatomas from other middle ear inflammatory diseases and for postoperative diagnosis of recurrent/residual cholesteatomas.

Predictors and clinical consequences of starting androgen therapy in men with low testosterone: results from the SIAMO-NOI registry.

PURPOSE: Management of late onset hypogonadism (LOH) is not homogenous. The aim of the study is to observe the management of patients with low testosterone (T) in highly specialized Italian centres. METHODS: The SIAMO-NOI is an observational longitudinal disease registry for the evaluation of the clinical management of patients with low T levels (total T < 12 nmol/L, calculated free T < 225 pmol/l or already in treatment) in 15 Italian centers members of the Italian Society for Andrology and Sexual Medicine (SIAMS). Clinical and biochemical data were collected for four visits during 12 months of observation. RESULTS: 432 patients (mean age 50.9 ± 14.9 years) were enrolled. Of them, 247 men were receiving androgen therapy, whereas 145 were naive. After the first visit (V0), 80 men started androgen therapy, whereas 55 remained untreated during the entire observation. Younger age [odds ratio (OR) 0.57 (0.35-0.92)], total T < 8 nmol/l [OR 4.69 (1.59-13.81)], complaining at least one sexual symptom [OR 11.55 (2.01-66.35)] and reporting more severe lower urinary tract symptoms [OR 1.27 (1.01-1.60)] predicted starting an androgen therapy. Sixty-four men started therapy immediately after V0 and maintained it until the observation end. When compared to V0, they reported an increase in all the domains of the International Index of Erectile Function-15 (IIEF-15), in the sexual and physical subdomains of the Aging Male Scale as well as in the International Prostate Symptom Score. Conversely, the untreated group reported a significant improvement, although lower than the treated group, only in the erectile function domain of the IIEF-15. CONCLUSIONS: Management of LOH in SIAMS centres is in line with the international guidelines and the newest knowledge about the role of T on prostate health. Androgen therapy is associated with an improvement in all the aspects of sexual life and in the perception of physical strength.

Quality of life and hormones after sex reassignment surgery.

BACKGROUND: Transpeople often look for sex reassignment surgery (SRS) to improve their quality of life (QoL). The hormonal therapy has many positive effects before and after SRS. There are no studies about correlation between hormonal status and QoL after SRS. AIM: To gather information on QoL, quality of sexual life and body image in transpeople at least 2 years after SRS,to compare these results with a control group and to evaluate the relations between the chosen items and hormonal status. SUBJECTS AND METHODS: Data from 60 transsexuals and from 60 healthy matched controls were collected. Testosterone,estradiol, LH and World Health Organization Quality of Life (WHOQOL-100) self-reported questionnaire were evaluated. Student's t test was applied to compare transsexuals and controls. Multiple regression model was applied to evaluate WHOQOL's chosen items and LH. RESULTS: The QoL and the quality of body image scores intranspeople were not statistically different from the matched control groups' ones. In the sexual life subscale,transwomen's scores were similar to biological women's ones, whereas transmen's scores were statistically lower than biological men's ones (P = 0.003). The quality of sexual life scored statistically lower in transmen than intranswomen (P = 0.048). A significant inverse relationship between LH and body image and between LH and quality of sexual life was found. CONCLUSIONS: This study highlights general satisfaction after SRS. In particular, transpeople's QoL turns out to be similar to Italian matched controls. LH resulted inversely correlated to body image and sexual life scores.