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BACKGROUND: Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre. METHODS: This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023. We evaluated clinical history, testicular ultrasound features, hormone levels, semen analysis, histological characteristics, staging, and treatments. mB-GCTs were compared with unilateral GCT patients with a follow-up longer than the median time-to-onset of the second tumour. RESULTS: Of 319 patients, 52 experienced B-GCT, with a median time-to-onset of the second tumour of 62 months (range: 8-229). The mB-GCT group showed higher gonadotropin levels (FSH 13.6mUI/mL vs. 7.4mUI/mL, p < 0.001; LH 6.6mUI/mL vs. 3.9mUI/mL, p = 0.004), lower sperm concentration (27 × 106/ejaculate vs. 78 × 106/ejaculate, p = 0.009), smaller residual testis volume (10.4 mL vs. 16.3 mL, p < 0.001), more inhomogeneous echotexture [57.5% vs. 14%, p < 0.001], and presence of microlithiasis (75% vs. 19.5%, p < 0.001). Kaplan-Meier curves confirmed that ultrasound features of the residual testis increased the cumulative risk of developing a second tumour. Microlithiasis was a strong independent predictor (OR 30.712, 95% CI 3.357-280.942, p = 0.002). CONCLUSIONS: Histological features of the first tumour or its treatment do not influence the onset of a second tumour. However, low residual testis volume, inhomogeneous echotexture, and microlithiasis significantly increase this risk. A comprehensive evaluation of the residual testis at baseline is essential for developing a personalised surveillance programme in GCT survivors, with regular ultrasound follow-up recommended beyond the conventional 5-year limit.
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Hemochromatosis (HC) is characterized by the progressive accumulation of iron in the body, resulting in organ damage. Endocrine complications are particularly common, especially when the condition manifests in childhood or adolescence, when HC can adversely affect linear growth or pubertal development, with significant repercussions on quality of life even into adulthood. Therefore, a timely and accurate diagnosis of these disorders is mandatory, but sometimes complex for hematologists without endocrinological support. This is a narrative review focused on puberty and growth disorders during infancy and adolescence aiming to offer guidance for diagnosis, treatment, and proper follow-up. Additionally, it aims to highlight gaps in the existing literature and emphasizes the importance of collaboration among specialists, which is essential in the era of precision medicine.
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Trastornos del Crecimiento , Sobrecarga de Hierro , Humanos , Adolescente , Niño , Sobrecarga de Hierro/etiología , Trastornos del Crecimiento/etiología , Trastornos del Crecimiento/fisiopatología , Masculino , Hemocromatosis/diagnóstico , Hemocromatosis/terapia , Femenino , Trastornos Gonadales/etiología , Pubertad/fisiología , PreescolarRESUMEN
BACKGROUND: Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial. OBJECTIVES: To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching to once-daily dual-release hydrocortisone on sexual function in outcome assessors blinded, randomized, multicenter, active comparator clinical trial. MATERIALS AND METHODS: Eighty-nine adrenal insufficiency patients on conventional, multiple daily doses of glucocorticoid replacement, enrolled in the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent in hypocortisolism (DREAM) trial, were randomly assigned to continue their therapy or to switch to an equivalent dose of dual-release hydrocortisone. Sixty-three patients (34 women) consented to sex steroid measurements and questionnaires completion for quality of life (Addison's disease-specific quality-of-life questionnaire) and sexual function evaluation (female sexual function index for women, International Index of Erectile Function-Erectile Function for men) at baseline and 24 weeks after randomization. RESULTS: At baseline, sexual dysfunction was observed in 41% of women and 59% of men with adrenal insufficiency. In both sexes, no associations were found between sexual function and hormone levels, whereas Addison's disease-specific quality-of-life questionnaire total and fatigue domain scores positively correlated with total female sexual function index and International Index of Erectile Function-Erectile Function scores. At 24 weeks, there was no significant difference either in sexual function or sex steroid levels between study groups. In the dual-release hydrocortisone group, the variation in the female sexual function index desire domain score was positively associated with the change in Addison's disease-specific quality-of-life questionnaire's symptom domain score (ρ = 0.478, p = 0.045). DISCUSSION: Sexual dysfunction is common in adrenal insufficiency patients and is likely explained by multiple factors. dual-release hydrocortisone treatment is not directly associated with sexual function improvement, but an indirect effect mediated by quality-of-life amelioration cannot be excluded.
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Acromegaly is a rare disease characterized by a diagnostic delay ranging from 5 to 10 years from the symptoms' onset. The aim of this study was to develop and internally validate machine-learning algorithms to identify a combination of variables for the early diagnosis of acromegaly. This retrospective population-based study was conducted between 2011 and 2018 using data from the claims databases of Sicily Region, in Southern Italy. To identify combinations of potential predictors of acromegaly diagnosis, conditional and unconditional penalized multivariable logistic regression models and three machine learning algorithms (i.e., the Recursive Partitioning and Regression Tree, the Random Forest and the Support Vector Machine) were used, and their performance was evaluated. The random forest (RF) algorithm achieved the highest Area under the ROC Curve value of 0.83 (95% CI 0.79-0.87). The sensitivity in the test set, computed at the optimal threshold of predicted probabilities, ranged from 28% for the unconditional logistic regression model to 69% for the RF. Overall, the only diagnosis predictor selected by all five models and algorithms was the number of immunosuppressants-related pharmacy claims. The other predictors selected by at least two models were eventually combined in an unconditional logistic regression to develop a meta-score that achieved an acceptable discrimination accuracy (AUC = 0.71, 95% CI 0.66-0.75). Findings of this study showed that data-driven machine learning algorithms may play a role in supporting the early diagnosis of rare diseases such as acromegaly.
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Acromegalia , Enfermedades Raras , Humanos , Estudios Retrospectivos , Acromegalia/diagnóstico , Diagnóstico Tardío , Algoritmos , Aprendizaje Automático , Prescripciones de Medicamentos , Diagnóstico Precoz , Sicilia/epidemiologíaRESUMEN
OBJECTIVE: High-grade aneuploidies of X and Y sex chromosomes (HGAs) are exceedingly rare and complex conditions. We aimed to investigate the effect of supernumerary X chromosomes (extra-Xs) on the clinical, hormonal, metabolic, and echocardiographic features of patients with HGAs. DESIGN AND METHODS: In a cross-sectional study, we compared 23 subjects with HGAs and 46 age-matched subjects with 47,XXY Klinefelter syndrome (KS), according to the number of extra-Xs: two (47,XXY and 48,XXYY), three (48,XXXY and 49,XXXYY), or four supernumerary Xs (49,XXXXY). A second cohort consisting of 46 pubertal stage-matched KS subjects was employed for validation. Clinical, hormonal, metabolic and ultrasonographic parameters were collected and analyzed. RESULTS: The increase in the number of extra-Xs was associated with a progressive adverse effect on height, pubertal development, testicular volume and function, adrenal steroidogenesis, and thyroid function. A progressive linear increase in ACTH and a decrease in cortisol/ACTH ratios were found. Weight and body mass index, Sertoli cell function, lipid profile, and glucose tolerance post-oral glucose tolerance test were all worse in the HGA cohort compared to KS. Cardiac evaluation revealed a linear association with reduced left and right end-diastolic diameters and reduced ejection fraction. CONCLUSION: The increase in the number of extra-Xs is associated with a "dose-dependent" progressive impairment in steroid producing glands, thyroid function, cardiac structure, and performance.
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Aneuploidia , Cromosomas Humanos X , Síndrome de Klinefelter , Humanos , Masculino , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/patología , Estudios Transversales , Adolescente , Cromosomas Humanos X/genética , Dosificación de Gen , Niño , Aberraciones Cromosómicas Sexuales , Adulto , Adulto JovenRESUMEN
Context: Patients with primary (PAI) and secondary adrenal insufficiency (SAI) experience bone metabolism alterations, possibly due to excessive replacement. Dual-release hydrocortisone (DR-HC) has shown promising effects on several parameters, but bone metabolism has seldom been investigated. Objective: We evaluated the long-term effects of once-daily DR-HC on bone in PAI and SAI. Methods: Patients on immediate-release glucocorticoid therapy were evaluated before and up to 6 years (range, 4-6) after switching to equivalent doses of DR-HC, yielding data on bone turnover markers, femoral and lumbar spine bone mineral density (BMD), and trabecular bone score (TBS). Results: Thirty-two patients (19 PAI, 18 female), median age 52 years (39.4-60.7), were included. At baseline, osteopenia was observed in 38% of patients and osteoporosis in 9%, while TBS was at least partially degraded in 41.4%. Higher body surface area-adjusted glucocorticoid doses predicted worse neck (P < .001) and total hip BMD (P < .001). Longitudinal analysis showed no significant change in BMD. TBS showed a trend toward decrease (P = .090). Bone markers were stable, albeit osteocalcin levels significantly varied. PAI and SAI subgroups behaved similarly, as did patients switching from hydrocortisone or cortisone acetate. Compared with men, women exhibited worse decline in TBS (P = .017) and a similar trend for neck BMD (P = .053). Conclusion: After 6 years of chronic DR-HC replacement, BMD and bone markers remained stable. TBS decline is more likely due to an age-related derangement of bone microarchitecture rather than a glucocorticoid effect. Our data confirm the safety of DR-HC replacement on bone health in both PAI and SAI patients.
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BACKGROUND: Neuroendocrine tumors (NETs) early diagnosis is a clinical challenge that require a deep understanding of molecular and genetic features of this heterogeneous group of neoplasms. However, few biomarkers exist to aid diagnosis and to predict prognosis and treatment response. In the oncological field, tumor-educated platelets (TEPs) have been implicated as central players in the systemic and local responses to tumor growth, thereby altering tumor specific RNA profile. Although TEPs have been found to be enriched in RNAs, few studies have investigated the potential of a type of RNA, circular RNAs (circRNA), as platelet-derived biomarkers for cancer. In this proof-of-concept study, we aim to demonstrate whether the circRNAs signature of tumor educated platelets can be used as a liquid biopsy biomarker for the detection of gastroenteropancreatic (GEP)-NETs and the prediction of the early response to treatment. METHODS: We performed a 24-months, prospective proof-of-concept study in men and women with histologically proven well-differentiated G1-G2 GEP-NET, aged 18-80 years, naïve to treatment. We performed a RNAseq analysis of circRNAs obtained from TEPs samples of 10 GEP-NETs patients at baseline and after 3 months from therapy (somatostatin analogs or surgery) and from 5 patients affected by non-malignant endocrinological diseases enrolled as a control group. RESULTS: Statistical analysis based on p < 0.05 resulted in the identification of 252 circRNAs differentially expressed between GEP-NET and controls of which 109 were up-regulated and 143 were down-regulated in NET patients. Further analysis based on an FDR value ≤ 0.05 resulted in the selection of 5 circRNAs all highly significant downregulated. The same analysis on GEP-NETs at baseline and after therapy in 5 patients revealed an average of 4983 remarkably differentially expressed circRNAs between follow-up and baseline samples of which 2648 up-regulated and 2334 down-regulated, respectively. Applying p ≤ 0.05 and FDR ≤ 0.05 filters, only 3/5 comparisons gave statistically significant results. CONCLUSIONS: Our findings identified for the first time a circRNAs signature from TEPs as potential diagnostic and predictive biomarkers for GEP-NETs.
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Tumores Neuroendocrinos , Masculino , Humanos , Femenino , Tumores Neuroendocrinos/genética , ARN Circular/genética , Plaquetas , Estudios Prospectivos , ARN/genéticaRESUMEN
Functional hypogonadotropic hypogonadism (FHH) is an increasingly frequent condition, whose pathological mechanisms are not yet fully clarified. The concept of FHH has now completely replaced that of late onset hypogonadism, that only concerned the ageing man. FHH is the result of an impairment of the hypothalamic-pituitary gonadal axis (HPG-A) function, resulting in decreased testosterone concentrations associated with low or inappropriately normal gonadotropin levels and infertility; it can be diagnosed once organic causes of hypogonadism are excluded. The growing occurrence of FHH derives from its association with widespread conditions, such as obesity and diabetes mellitus, but also to the increasing ease and frequency of use of several drugs, such as opioids, glucocorticoids, and sex steroids. Moreover, given the tendency of many subjects to excessive physical activity and drastic reduction in caloric intake, FHH may also be secondary to low energy availability. Finally, the association with HIV infection should not be overlooked. Therefore, there is an important variability in the diseases that can lead to FHH. Despite the heterogeneity of the underlying pathologies, the mechanisms leading to FHH would seem quite similar, with the initial event represented by the impairment at the HPG-A level. Nevertheless, many different biological pathways are involved in the pathogenesis of FHH, therefore the aim of the current paper is to provide an overview of the main relevant mechanisms, through a detailed analysis of the literature, focusing specifically on pathogenesis and clinical, diagnostic and therapeutic aspects.
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Infecciones por VIH , Hipogonadismo , Infertilidad Masculina , Masculino , Humanos , Infecciones por VIH/complicaciones , Hipogonadismo/etiología , Hormonas Esteroides Gonadales , Infertilidad Masculina/etiología , Obesidad/complicacionesRESUMEN
Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a ß subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.
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CONTEXT: It has been claimed that thyroid dysfunction contributes to the spectrum of Klinefelter syndrome (KS); however, studies are scarce. OBJECTIVE: In a retrospective longitudinal study, we aimed at describing the hypothalamic-pituitary-thyroid (HPT) axis and thyroid ultrasonographic (US) appearance in patients with KS throughout the life span. METHODS: A total of 254 patients with KS (25.9 ± 16.1 years) were classified according to their pubertal and gonadal status and compared with different groups of non-KS age-matched individuals with normal thyroid function, treated and untreated hypogonadism, or chronic lymphocytic thyroiditis. We assessed serum thyroid hormone levels, antithyroid antibodies, US thyroid parameters, and in vitro pituitary type 2 deiodinase (D2) expression and activity. RESULTS: Thyroid autoimmunity was more prevalent among individuals with KS at all ages, although the antibody (Ab)-negative vs Ab-positive cohorts were not different. Signs of thyroid dysfunction (reduced volume, lower echogenicity, and increased inhomogeneity) were more prominent in KS than in euthyroid controls. Free thyroid hormones were lower in prepubertal, pubertal, and adult patients with KS, whereas thyrotropin values were lower only in adults. Peripheral sensitivity to thyroid hormones was unaltered in KS, suggesting a dysfunctional HPT axis. Testosterone (T) was the only factor associated with thyroid function and appearance. In vitro testing demonstrated an inhibitory effect of T on pituitary D2 expression and activity, supporting enhanced central sensing of circulating thyroid hormones in hypogonadism. CONCLUSION: From infancy through adulthood, KS is characterized by increased morphofunctional abnormalities of the thyroid gland, combined with a central feedback dysregulation sustained by the effect of hypogonadism on D2 deiodinase.
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Hipogonadismo , Síndrome de Klinefelter , Enfermedades de la Tiroides , Adulto , Humanos , Lactante , Estudios Retrospectivos , Estudios Longitudinales , Retroalimentación , Hormonas Tiroideas , Testosterona , Enfermedades de la Tiroides/complicacionesRESUMEN
OBJECTIVE: Klinefelter syndrome is the most common chromosomal disorder in males and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal, and quantitative ultrasound data in a life-course perspective. DESIGN: Prospective semilongitudinal study. METHODS: We included 155 subjects with 47,XXY karyotype (age range: 7 months-55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal, and testicular ultrasound (US) assessments were performed. RESULTS: Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/follicle-stimulating hormone ratio thereafter. The testosterone/luteinizing hormone ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level. CONCLUSIONS: The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients.
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Hipogonadismo , Síndrome de Klinefelter , Enfermedades Testiculares , Masculino , Adulto , Humanos , Niño , Lactante , Síndrome de Klinefelter/tratamiento farmacológico , Estudios Prospectivos , Testículo/diagnóstico por imagen , Testículo/patología , Hipogonadismo/tratamiento farmacológico , Testosterona/uso terapéutico , Hormona Folículo Estimulante , Enfermedades Testiculares/diagnóstico por imagen , Enfermedades Testiculares/patología , Inhibinas , PubertadRESUMEN
BACKGROUND: SARS-CoV-2 related immunopathology may be the driving cause underlying severe COVID-19. Through an immunophenotyping analysis on paired bronchoalveolar lavage fluid (BALF) and blood samples collected from mechanically ventilated patients with COVID-19-associated Acute Respiratory Distress Syndrome (CARDS), this study aimed to evaluate the cellular immune responses in survivors and non-survivors of COVID-19. METHODS: A total of 36 paired clinical samples of bronchoalveolar lavage fluid (BALF) mononuclear cells (BALF-MC) and peripheral blood mononuclear cells (PBMC) were collected from 18 SARS-CoV-2-infected subjects admitted to the intensive care unit (ICU) of the Policlinico Umberto I, Sapienza University Hospital in Rome (Italy) for severe interstitial pneumonia. The frequencies of monocytes (total, classical, intermediate and non-classical) and Natural Killer (NK) cell subsets (total, CD56bright and CD56dim), as well as CD4+ and CD8+ T cell subsets [naïve, central memory (TCM) and effector memory (TEM)], and those expressing CD38 and/or HLADR were evaluated by multiparametric flow cytometry. RESULTS: Survivors with CARDS exhibited higher frequencies of classical monocytes in blood compared to non-survivors (p < 0.05), while no differences in the frequencies of the other monocytes, NK cell and T cell subsets were recorded between these two groups of patients (p > 0.05). The only exception was for peripheral naïve CD4+ T cells levels that were reduced in non-survivors (p = 0.04). An increase in the levels of CD56bright (p = 0.012) and a decrease in CD56dim (p = 0.002) NK cell frequencies was also observed in BALF-MC samples compared to PBMC in deceased COVID-19 patients. Total CD4+ and CD8+ T cell levels in the lung compartment were lower compared to blood (p = 0.002 and p < 0.01, respectively) among non-survivors. Moreover, CD38 and HLA-DR were differentially expressed by CD4+ and CD8+ T cell subsets in BALF-MC and in PBMC among SARS-CoV-2-infected patients who died from COVID-19 (p < 0.05). CONCLUSIONS: These results show that the immune cellular profile in blood and pulmonary compartments was similar in survivors and non-survivors of COVID-19. T lymphocyte levels were reduced, but resulted highly immune-activated in the lung compartment of patients who faced a fatal outcome.
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This paper describes the process, advantages and limitations of a qualitative methodology for defining and analyzing vulnerabilities during the COVID-19 pandemic. Implemented in Italy in two sites (Rome and outside Rome, in some small-medium sized municipalities in Latium) in 2021, this investigation employed a mixed digital research tool that was also used simultaneously in four other European countries. Its digital nature encompasses both processes of data collection. Among the most salient is that the pandemic catalyzed new vulnerabilities in addition to exacerbating old ones, particularly economic. Many of the vulnerabilities detected, in fact, are linked to previous situations, such as the uncertainties of labor markets, having in COVID-19 to the greatest negative effects on the most precarious workers (non-regular, part-time, and seasonal). The consequences of the pandemic are also reflected in other forms of vulnerability that appear less obvious, having exacerbated social isolation, not only out of fear of contagion, but because of the psychological challenges posed by containment measures themselves. These measures created not mere discomfort, but behavioral changes characterized by anxiety, fearfulness, and disorientation. More generally, this investigation reveals the strong influence of social determinants throughout the COVID-19 pandemic, creating new forms of vulnerability, as the effects of social, economic, and biological risk factors were compounded, in particular, among already marginalized populations.
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Background: The aim of this study was to evaluate (i) the prevalence of subjects with a positive sperm culture (SC) for bacteria in subjects with or without genitourinary tract inflammation (GTI); (ii) the actual distribution of the species analysed, according to Gram stain; (iii) the impact on sperm parameters; and (iv) the actual bacterial susceptibility to antibiotics. Methods: A total of 930 subjects (1855) years, were retrospectively studied. All the patients underwent SC and in the case of positive tests (CFU > 106), a microbiological susceptibility analysis. The subjects studied were subdivided into group A (n = 452), with subjective signs of GTI; group B (n = 478), male partners of infertile couples; and group C, 30 healthy normospermic subjects. In group B and in the control group, a semen analysis was performed. Results: Overall, the prevalence of positive SC was 21.5% (200/930). The prevalence of positive SC in group A (113/200; 56.5%) was significantly higher vs. group B (87/200; 43.5%; p = 0.01) and control group (1/30; 3.3%; p = 0.0001). In subjects with GTI, the prevalence of asthenozoospermic (96/285; 33.7%) and oligo-asthenozoospermic (98/285; 34.4%) was significantly higher vs. normospermic, oligo-astheno-teratozoospermic, oligozoospermic and azoospermic subjects (22/285 (7.7%), 48/285 (16.8%), 15/285 (5.3%) and 6/285 (2.1%), respectively; p = 0.001). Finally, Enterococcus faecalis (Gram-positive) and Escherichia coli (Gram-negative) showed the highest prevalence of antibiotic resistance. Conclusions: The prevalence of positive SC is higher in GTI subjects; however, the SC could also be positive in subjects without GTI. Commonly used antibiotics have an increasing risk of being useless for the treatment of bacterial infections. Finally, the diagnosis of GTIs is important also for male fertility.(AU)
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Humanos , Masculino , Adulto , Persona de Mediana Edad , Semen , Análisis de Semen , Antibacterianos , Infertilidad Masculina , Infecciones Bacterianas , Pruebas de Sensibilidad Microbiana , Microbiología , Técnicas MicrobiológicasRESUMEN
BACKGROUND: Erectile dysfunction is recognized as one of the complications of diabetes mellitus. To date, a wide gap of knowledge is present on the efficacy of pharmacological treatments of diabetes mellitus on erectile function, acting not only through metabolic control. Similarly, the effects of different diet regimens on erectile dysfunction are still debated. OBJECTIVES: We aimed to explore the effects of diet and antihyperglycemic drugs, considering both old and novel therapeutic approaches, on erectile function. MATERIALS/METHODS: We performed a systematic review, following the PRISMA guidelines. The research was conducted on studies reporting erectile dysfunction assessment in subjects with diabetes and the relationship with diet and antihyperglycemic drugs. RESULTS: The Mediterranean diet was effective in most studies for the protection of erectile function. Furthermore, antihyperglycemic drugs seem to show an overall protective role on erectile function. DISCUSSION/CONCLUSION: Although encouraging results are present for all classes of antihyperglycemic drugs, several studies are needed in humans, mainly on acarbose, pioglitazone, dipeptidyl-peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors.
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Diabetes Mellitus Tipo 2 , Dieta Mediterránea , Disfunción Eréctil , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Masculino , Humanos , Hipoglucemiantes/uso terapéutico , Disfunción Eréctil/tratamiento farmacológico , Disfunción Eréctil/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
BACKGROUND: The aim of this study was to evaluate (i) the prevalence of subjects with a positive sperm culture (SC) for bacteria in subjects with or without genitourinary tract inflammation (GTI); (ii) the actual distribution of the species analysed, according to Gram stain; (iii) the impact on sperm parameters; and (iv) the actual bacterial susceptibility to antibiotics. METHODS: A total of 930 subjects (18-55) years, were retrospectively studied. All the patients underwent SC and in the case of positive tests (CFU > 106), a microbiological susceptibility analysis. The subjects studied were subdivided into group A (n = 452), with subjective signs of GTI; group B (n = 478), male partners of infertile couples; and group C, 30 healthy normospermic subjects. In group B and in the control group, a semen analysis was performed. RESULTS: Overall, the prevalence of positive SC was 21.5% (200/930). The prevalence of positive SC in group A (113/200; 56.5%) was significantly higher vs. group B (87/200; 43.5%; p = 0.01) and control group (1/30; 3.3%; p = 0.0001). In subjects with GTI, the prevalence of asthenozoospermic (96/285; 33.7%) and oligo-asthenozoospermic (98/285; 34.4%) was significantly higher vs. normospermic, oligo-astheno-teratozoospermic, oligozoospermic and azoospermic subjects (22/285 (7.7%), 48/285 (16.8%), 15/285 (5.3%) and 6/285 (2.1%), respectively; p = 0.001). Finally, Enterococcus faecalis (Gram-positive) and Escherichia coli (Gram-negative) showed the highest prevalence of antibiotic resistance. CONCLUSIONS: The prevalence of positive SC is higher in GTI subjects; however, the SC could also be positive in subjects without GTI. Commonly used antibiotics have an increasing risk of being useless for the treatment of bacterial infections. Finally, the diagnosis of GTIs is important also for male fertility.
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Infertilidad Masculina , Humanos , Masculino , Infertilidad Masculina/diagnóstico , Semen , Prevalencia , Estudios Retrospectivos , Espermatozoides , BacteriasRESUMEN
Cyclic adenosine monophosphate/Protein kinase A (cAMP/PKA) signaling pathway is the master regulator of endocrine tissue function. The level, compartmentalization and amplitude of cAMP response are finely regulated by phosphodiesterases (PDEs). PDE8 is responsible of cAMP hydrolysis and its expression has been characterized in all steroidogenic cell types in rodents including adrenal and Leydig cells in rodents however scarce data are currently available in humans. Here we demonstrate that human Leydig cells express both PDE8A and PDE8B isoforms. Interestingly, we found that the expression of PDE8B but not of PDE8A is increased in transformed Leydig cells (Leydig cell tumors-LCTs) compared to non-tumoral cells. Immunofluorescence analyses further reveals that PDE8A is also highly expressed in specific spermatogenic stages. While the protein is not detected in spermatogonia it accumulates nearby the forming acrosome, in the trans-Golgi apparatus of spermatocytes and spermatids and it follows the fate of this organelle in the later stages translocating to the caudal part of the cell. Taken together our findings suggest that 1) a specific pool(s) of cAMP is/are regulated by PDE8A during spermiogenesis pointing out a possible new role of this PDE8 isoform in key events governing the differentiation and maturation of human sperm and 2) PDE8B can be involved in Leydig cell transformation.
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3',5'-AMP Cíclico Fosfodiesterasas , Tumor de Células de Leydig , Humanos , Masculino , 3',5'-AMP Cíclico Fosfodiesterasas/genética , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Adenosina Monofosfato , Tumor de Células de Leydig/genética , Isoformas de Proteínas , SemenRESUMEN
Acromegaly is a rare disease characterized by an excessive production of growth-hormone and insulin-like growth factor 1, typically resulting from a GH-secreting pituitary adenoma. This study was aimed at comparing and measuring accuracy of newly and previously developed coding algorithms for the identification of acromegaly using Italian claims databases. This study was conducted between January 2015 and December 2018, using data from the claims databases of Caserta Local Health Unit (LHU) and Sicily Region in Southern Italy. To detect acromegaly cases from the general target population, four algorithms were developed using combinations of diagnostic, surgical procedure and co-payment exemption codes, pharmacy claims and specialist's visits. Algorithm accuracy was assessed by measuring the Youden Index, sensitivity, specificity, positive and negative predictive values. The percentage of positive cases for each algorithm ranged from 7.9 (95% CI 6.4-9.8) to 13.8 (95% CI 11.7-16.2) per 100,000 inhabitants in Caserta LHU and from 7.8 (95% CI 7.1-8.6) to 16.4 (95% CI 15.3-17.5) in Sicily Region. Sensitivity of the different algorithms ranged from 71.1% (95% CI 54.1-84.6%) to 84.2% (95% CI 68.8-94.0%), while specificity was always higher than 99.9%. The algorithm based on the presence of claims suggestive of acromegaly in ≥ 2 different databases (i.e., hospital discharge records, copayment exemptions registry, pharmacy claims and specialist visits registry) achieved the highest Youden Index (84.2) and the highest positive predictive value (34.8; 95% CI 28.6-41.6). We tested four algorithms to identify acromegaly cases using claims databases with high sensitivity and Youden Index. Despite identifying rare diseases using real-world data is challenging, this study showed that robust validity testing may yield the identification of accurate coding algorithms.
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Acromegalia , Adenoma , Hormona de Crecimiento Humana , Acromegalia/diagnóstico , Acromegalia/epidemiología , Adenoma/diagnóstico , Adenoma/epidemiología , Algoritmos , Bases de Datos Factuales , Humanos , Factor I del Crecimiento Similar a la Insulina , SiciliaRESUMEN
During the COVID-19 pandemic, the most severe form of the disease was most often seen in male patients. The aim of this study was to identify any male predispositions that could be used to predict the outcome of the disease and enable early intervention. We investigated CAG polymorphism in the androgen receptor gene and serum levels of testosterone and LH, which were considered as probably responsible for this predisposition. The study involved 142 patients who had recovered from COVID-19 at least three months previously and were classified according to their disease severity using the World Health Organization (WHO) classification. We observed a significant increase in the number of CAG repeats with increasing disease severity: the percentage of patients with more than 23 repeats increased two-fold from Grade I to Grade IV. Furthermore, testosterone levels were significantly lower in patients with severe disease. Reduced androgenic signaling could predispose men to a more severe form: low testosterone levels and a reduced androgen receptor activity (CAG > 23) expose the host to an excessive inflammatory response, leading downstream to the multi-organ damage seen in severe COVID-19.
RESUMEN
OBJECTIVES: The potential clinical effects of licorice (Glycyrrhiza spp.) and its extracts have been investigated since ancient times. Whether pseudohyperaldosteronism, with consequent arterial hypertension, is the only endocrine effect produced by licorice is uncertain, and a role in the reproductive system has been proposed. This review aimed to summarize the current knowledge on the pharmacologic effects of licorice on male and female reproductive systems. METHODS: Overall, 1462 records were extracted from electronic databases and systematically examined. A total of 28 studies were included in the final analysis. RESULTS: Preclinical and clinical studies revealed estrogen-like activity of licorice components, especially flavonoids, isoflavonoids, and chalcones, showing a potential role of licorice in ameliorating symptoms associated with estrogen insufficiency. Preclinical studies also showed weak antiandrogen properties and beneficial effects of licorice on gonadal function in both sexes, but clinical studies yield to poor and conflicting results depending on the type and dose of licorice. CONCLUSIONS: Licorice consumption can affect the reproductive system. However, its role needs to be further explored, especially due to the great variability of bioactive compounds used in existing studies.