The detection rate for prostate cancer in systematic and targeted prostate biopsy in biopsy-naive patients, according to the localization of the lesion at the mpMRI: A single-center retrospective observational study.

OBJECTIVE: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients. MATERIAL AND METHODS: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy. RESULTS: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018. CONCLUSION: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores.

Ischemia-Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets.

Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia-reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) ß-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia-reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process.

Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

Preoperative Albumin-to-Alkaline Phosphatase Ratio as an Independent Predictor of Lymph Node Involvement in Penile Cancer.

Background and Objectives: To investigate the role of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in predicting pathologic node-positive (pN+) disease in penile cancer (PC) patients undergoing inguinal lymph node dissection (ILND). Materials and Methods: Clinical data of patients with squamous cell carcinoma (SCC) PC + ILND at a single high-volume institution between 2016 and 2021 were collected and retrospectively analyzed. An AAPR was obtained from preoperative blood analyses performed within 30 days from their scheduled surgery. A ROC curve analysis was used to assess AAPR cutoff, in addition to the Youden Index. Logistic regression analysis was utilized for an odds ratio (OR), 95% confidence interval (CI) calculations, and an estimate of pN+ disease. A p value < 0.05 was considered to be as statistically significant. Results: Overall, 42 PC patients were included in the study, with a mean age of 63.6 ± 12.9 years. The AAPR cut-off point value was determined to be 0.53. The ROC curve analysis reported an AUC of 0.698. On multivariable logistic regression analysis lymphovascular invasion (OR = 5.38; 95% CI: 1.47-9.93, p = 0.022), clinical node-positive disease (OR = 13.68; 95% CI: 4.37-43.90, p < 0.009), and albumin-to-alkaline phosphatase ratio ≤ 0.53 (OR = 3.61; 95% CI: 1.23-12.71, p = 0.032) were predictors of pN+ involvement. Conclusions: Preoperative AAPR may be a potentially valuable prognostic marker of pN+ disease in patients who underwent surgery for PC.

Carbapenem-Resistant Enterobacteriaceae in Urinary Tract Infections: From Biological Insights to Emerging Therapeutic Alternatives.

Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.

Sexual desire, mood disorders and sleep disturbances in female BMS patients: A controlled study.

BACKGROUND: Burning mouth syndrome is a chronic orofacial pain with intraoral burning and other oral dysaesthetic symptoms that significantly affects the quality of life. The aim of this study is to evaluate the sexual desire in women with BMS and to investigate the possible related factors. METHODS: A case-control study was performed. BMS patients were enrolled according to the International Classification of OroFacial Pain criteria. Demographic variables were collected. We evaluated pain with the Numeric Rating Scale (NRS), Visual Analogue Scale (VAS) and Total Pain Rating Index (T-PRI), anxiety and depression using the Hospital Anxiety and Depression Scale (HADS-A e HADS-D), sleep disturbances with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), and sexual desire using Sexual Desire Inventory (SDI). RESULTS: A total of 50 BMS women and 50 healthy controls were enrolled. Compared with the controls, the BMS patients showed higher scores in the NRS (7,81 ± 1,71 vs. 0,14 ± 0.40; p < 0.0001), TPR-I (10,50 ± 4,86 vs. 0,36 ± 1,06; p < 0.0001), HADS-A (11,86 ± 2,85 vs. 3,90 ± 2,81; p < 0.0001), HADS-D (8,04 ± 3,18 vs. 1,42 ± 1,86; p < 0.0001) and PSQI (9,04 ± 2,62 vs. 4,64 ± 3,27; p < 0.0001). The mean SDI in the study group was significantly lower compared to healthy controls (32,36 ± 14,45 vs. 69,70 ± 19,94; p < 0.0001). No correlation was found between SDI and others items explored. CONCLUSION: In line with previous studies, anxiety, depression and sleep disturbances are more common in BMS patients than in healthy population. This pilot study demonstrates for the first time an association between BMS and low sexual desire.

Radiogenomics in Renal Cancer Management-Current Evidence and Future Prospects.

Renal cancer management is challenging from diagnosis to treatment and follow-up. In cases of small renal masses and cystic lesions the differential diagnosis of benign or malignant tissues has potential pitfalls when imaging or even renal biopsy is applied. The recent artificial intelligence, imaging techniques, and genomics advancements have the ability to help clinicians set the stratification risk, treatment selection, follow-up strategy, and prognosis of the disease. The combination of radiomics features and genomics data has achieved good results but is currently limited by the retrospective design and the small number of patients included in clinical trials. The road ahead for radiogenomics is open to new, well-designed prospective studies, with large cohorts of patients required to validate previously obtained results and enter clinical practice.

Risk Factors for Testicular Cancer: Environment, Genes and Infections-Is It All?

The incidence of testicular cancer is steadily increasing over the past several decades in different developed countries. If on one side better diagnosis and treatment have shone a light on this disease, on the other side, differently from other malignant diseases, few risk factors have been identified. The reasons for the increase in testicular cancer are however unknown while risk factors are still poorly understood. Several studies have suggested that exposure to various factors in adolescence as well as in adulthood could be linked to the development of testicular cancer. Nevertheless, the role of environment, infections, and occupational exposure are undoubtedly associated with an increase or a decrease in this risk. The aim of this narrative review is to summarize the most recent evidence regarding the risk factors associated with testicular cancer, starting from the most commonly evaluated (cryptorchidism, family history, infections) to the newer identified and hypothesized risk factors.

Cytoreductive Nephrectomy and Metastatic Renal Cell Carcinoma: State of the Art and Future Perspectives.

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.

The Role of miRNA in Testicular Cancer: Current Insights and Future Perspectives.

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

The relationship between obstructive sleep apnoea and erectile dysfunction: An underdiagnosed link? A prospective cross-sectional study.

This cross-sectional study aimed to investigate the prevalence and clinical characteristics of erectile dysfunction in patients with obstructive sleep apnoea. We enrolled 133 male patients with suspected obstructive sleep apnoea. Ear, nose and throat evaluation, laboratory tests, body mass index, Epworth sleepiness scale, 5-international index of erectile function, overnight ambulatory polygraphy and drug-induced sleep endoscopy patterns were assessed. Eighty patients reported obstructive sleep apnoea. 60% (n = 48) reported erectile dysfunction. Statistically significant correlations were found between 5-International Index of Erectile Function and age, hypertension, diabetes, Epworth sleepiness scale, apnoea-hypopnea index score, O2 saturation-nadir, and oxygen desaturation index. Age, diabetes and O2 saturation-nadir were independent predictors of erectile function. Epworth sleepiness scale, apnoea-hypopnea index score, O2 saturation-nadir, oxygen desaturation index and albumin were higher compared to patients without erectile dysfunction. No statistically significant differences were reported for drug-induced sleep endoscopy patterns and erectile dysfunction. Patients with obstructive sleep apnoea were at significant risk of having erectile dysfunction. Males with obstructive sleep apnoea should be investigated for erectile dysfunction.

Novel Therapeutic Opportunities in Neoadjuvant Setting in Urothelial Cancers: A New Horizon Opened by Molecular Classification and Immune Checkpoint Inhibitors.

Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum-Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification.

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

Micro-Ultrasound in the Diagnosis and Staging of Prostate and Bladder Cancer: A Comprehensive Review.

Background and Objectives: Multiparametric magnetic resonance imaging (mpMRI) of the prostate and prostate-specific membrane antigen positron emission tomography (PSMA PET) are some examples of how the advancement of imaging techniques have revolutionized the diagnosis, staging, and consequently management of patients with prostate cancer (PCa). Although with less striking results, novel radiological modalities have also been proposed for bladder cancer (BCa) in recent years. Micro-ultrasound (MUS) is an imaging examination characterized by high real-time spatial resolution, recently introduced in the urological field. This article aimed to describe the current evidence regarding the application of MUS for the diagnosis and staging of PCa and BCa. Materials and Methods: We designed a narrative review. A comprehensive search in the MEDLINE, Scopus, and Cochrane Library databases was performed. Articles in English-language and published until July 2022 were deemed eligible. Retrospective and prospective primary clinical studies, as well as meta-analyses, were included. Results: MUS-guided prostate biopsy showed high sensitivity (0.91, 95% CI, 0.79-0.97) in the diagnosis of clinically significant PCa (csPCa). It was associated with a higher detection rate of csPCa than a systematic biopsy (1.18, 95% CI 0.83-1.68). No significant difference was found between MUS and mpMRI-guided biopsy in the total detection of PCa (p = 0.89) and in the detection of Grade Groups ≥ 2 (p = 0.92). The use of MUS to distinguish between non-muscle-invasive and muscle-invasive BCa was described, highlighting an up-staging with MUS only in a minority of cases (28.6%). Conclusions: Promising findings have emerged regarding the feasibility and accuracy of MUS in the diagnosis and staging of PCa and BCa. However, the available evidence is limited and should be considered preliminary.

Preoperative Fibrinogen-to-Albumin Ratio as Potential Predictor of Bladder Cancer: A Monocentric Retrospective Study.

Background and objective: Fibrinogen and albumin are two proteins widely used, singularly and in combination, in cancer patients as biomarkers of nutritional status, inflammation and disease prognosis. The aim of our study was to investigate the preoperative fibrinogen-to-albumin ratio (FAR) as a preoperative predictor of malignancy as well as advanced grade in patients with bladder cancer. Materials and Methods: A retrospective analysis of patients who underwent TURBT at our institution between 2017 and 2021 was conducted. FAR was obtained from preoperative venous blood samples performed within 30 days from scheduled surgery and was analyzed in relation to histopathological reports, as was the presence of malignancy. Statistical analysis was performed using a Kruskal−Wallis Test, and univariate and multivariate logistic regression analysis, assuming p < 0.05 to be statistically significant. Results: A total of 510 patients were included in the study (81% male, 19% female), with a mean age of 71.66 ± 11.64 years. The mean FAR was significantly higher in patients with low-grade and high-grade bladder cancer, with values of 80.71 ± 23.15 and 84.93 ± 29.96, respectively, compared to patients without cancer (75.50 ± 24.81) (p = 0.006). Univariate regression analysis reported FAR to be irrelevant when considered as a continuous variable (OR = 1.013, 95% CI = 1.004−1.022; p = 0.004), while when considered as a categorical variable, utilizing a cut-off set at 76, OR was 2.062 (95% CI = 1.378−3.084; p < 0.0001). Nevertheless, the data were not confirmed in the multivariate analysis. Conclusions: Elevated preoperative FAR is a potential predictor of malignancy as well as advanced grade in patients with bladder cancer. Further data are required to suggest a promising role of the fibrinogen-to-albumin ratio as a diagnostic biomarker for bladder tumors.

Urinary Incontinence after Planned Cesarean Hysterectomy for Placenta Accreta.

INTRODUCTION: Data regarding the risk of incontinence after cesarean hysterectomy are lacking. We aimed to assess the risk of urinary incontinence in women who underwent planned cesarean hysterectomy for placenta accreta. METHODS: This was a retrospective study of women who underwent planned cesarean hysterectomy for placenta accreta. The primary outcome was the incidence of post-cesarean hysterectomy urinary incontinence, defined as involuntary loss of urine between 3 and 12 months after cesarean hysterectomy. Outcomes were compared in a cohort of women who underwent planned cesarean hysterectomy for placenta accreta with a control group of women who underwent scheduled cesarean section without hysterectomy. RESULTS: Forty-seven singleton gestations who underwent planned cesarean hysterectomy for placenta accrete were included in the study and were compared with 100 controls. Eight cases of bladder injuries were reported, 7 in the planned cesarean hysterectomy group and one in the planned cesarean delivery group. Overall, urinary incontinence was reported in 10 women of the planned cesarean hysterectomy group and in 8 women of the planned cesarean section group (21.3% vs. 8.0%; p = 0.03). CONCLUSION: Planned cesarean hysterectomy for placenta accreta is a risk factor for urinary incontinence.

The Comparison of Imaging and Clinical Methods to Estimate Prostate Volume: A Single-Centre Retrospective Study.

BACKGROUND: Prostate volume (PV) is a useful tool in risk stratification, diagnosis, and follow-up of numerous prostatic diseases including prostate cancer and benign prostatic hypertrophy. There is currently no accepted ideal PV measurement method. OBJECTIVE: This study compares multiple means of PV estimation, including digital rectal examination (DRE), transrectal ultrasound (TRUS), and magnetic resonance imaging (MRI), and radical prostatectomy specimens to determine the best volume measurement style. METHODS: A retrospective, observational, single-site study with patients identified using an institutional database was performed. A total of 197 patients who underwent robot-assisted radical prostatectomy were considered. Data collected included age, serum PSA at the time of the prostate biopsy, clinical T stage, Gleason score, and PVs for each of the following methods: DRE, TRUS, MRI, and surgical specimen weight (SPW) and volume. RESULTS: A paired t test was performed, which reported a statistically significant difference between PV measures (DRE, TRUS, MRI ellipsoid, MRI bullet, SP ellipsoid, and SP bullet) and the actual prostate weight. Lowest differences were reported for SP ellipsoid volume (M = -2.37; standard deviation [SD] = 10.227; t[167] = -3.011; and p = 0.003), MRI ellipsoid volume (M = -4.318; SD = 9.53; t[167] = -5.87; and p = 0.000), and MRI bullet volume (M = 5.31; SD = 10.77; t[167] = 6.387; and p = 0.000). CONCLUSION: The PV obtained by MRI has proven to correlate with the PV obtained via auto-segmentation software as well as actual SPW, while also being more cost-effective and time-efficient. Therefore, demonstrating that MRI estimated the PV is an adequate method for use in clinical practice for therapeutic planning and patient follow-up.

Prostate Cancer Radiogenomics-From Imaging to Molecular Characterization.

Radiomics and genomics represent two of the most promising fields of cancer research, designed to improve the risk stratification and disease management of patients with prostate cancer (PCa). Radiomics involves a conversion of imaging derivate quantitative features using manual or automated algorithms, enhancing existing data through mathematical analysis. This could increase the clinical value in PCa management. To extract features from imaging methods such as magnetic resonance imaging (MRI), the empiric nature of the analysis using machine learning and artificial intelligence could help make the best clinical decisions. Genomics information can be explained or decoded by radiomics. The development of methodologies can create more-efficient predictive models and can better characterize the molecular features of PCa. Additionally, the identification of new imaging biomarkers can overcome the known heterogeneity of PCa, by non-invasive radiological assessment of the whole specific organ. In the future, the validation of recent findings, in large, randomized cohorts of PCa patients, can establish the role of radiogenomics. Briefly, we aimed to review the current literature of highly quantitative and qualitative results from well-designed studies for the diagnoses, treatment, and follow-up of prostate cancer, based on radiomics, genomics and radiogenomics research.

Hypogonadism in Patients with Prader Willi Syndrome: A Narrative Review.

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.

Osteoporosis is a Predictive Factor for Nephrolithiasis in an Adult Free-Living Caucasian Population From Southern Italy: A Longitudinal Retrospective Study Based on a General Practice Database.

Osteoporosis and nephrolithiasis are common multifactorial disorders with high incidence and prevalence in the adult population worldwide. Both are associated with high morbidity and mortality if not correctly diagnosed and accurately treated. Nephrolithiasis is considered a risk factor for reduced bone mineral density. Aim of this retrospective longitudinal study was to evaluate if osteoporosis is a predictive factor for the nephrolithiasis occurrence. Free-living subjects referring to "COMEGEN" general practitioners cooperative operating in Naples, Southern Italy. Twelve thousand seven hundred ninety-four Caucasian subjects (12,165 female) who performed bone mineral density by dual-energy X-ray absorptiometry and have a negative personal history for nephrolithiasis. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary osteoporosis were excluded from the study. In a mean lapse of time of 19.5 months, 516 subjects had an incident episode of nephrolithiasis. Subjects with osteoporosis had an increased risk of nephrolithiasis than subjects without osteoporosis (Hazard Ratio = 1.33, 95% Confidence Interval 1.01-1.74, p = 0.04). Free-living adult subjects over the age of 40 with idiopathic osteoporosis have an increased risk of incident nephrolithiasis, suggesting the advisability of appropriate investigation and treatment of the metabolic alterations predisposing to nephrolithiasis in patients with osteoporosis. The study protocol was approved by the ASL Napoli 1 Ethical Committee, protocol number 0018508/2018.