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Oxidative stress (OS) can have an impact in the pathogenesis and in the progression of thyroid cancer. We investigated the levels of reactive oxygen species (ROS) in 50 malignant and benign thyroid lesions and 41 normal tissues, and correlated them with the thyroid differentiation score-TDS and the clinico-pathologic features. NOX4 expression, GPx activity and the genetic pattern of tumors were evaluated. In malignant and benign lesions, ROS generation and NOX4 protein expression were higher than in normal tissues. Follicular (FTCs) and anaplastic/poorly differentiated cancers had increased OS relative to papillary tumors (PTCs). Moreover, OS in FTCs was higher than in follicular adenomas. Mutated PTCs showed increased OS compared with non-mutated PTCs. In malignant tumors, OS was inversely correlated with TDS, and directly correlated with tumor stage and ATA risk. GPx activity was increased in tumors compared with normal tissues, and inversely correlated to OS. In conclusion, our data indicate that thyroid tumors are exposed to higher OS compared with normal tissues, while showing a compensative increased GPx activity. OS correlates with tumor aggressiveness and mutations in the MEK-ERK pathway in PTC. The inverse correlation between OS and TDS suggests that ROS may repress genes involved in thyroid differentiation.

Due to the heterogeneous distribution of seminiferous tubules in patients with non-obstructive azoospermia (NOA), retrieving enough good quality sperm for ICSI may require a complete testicular dissection. According to a the only available study in this field, sperm may be found in the testis surface in 34.2% of patients, while a deeper testicular dissection is able to provide sperm for ICSI in 28% of those without sperm in the testis surface.to determine the probability of finding enough sperm for ICSI at the initial wide incision of the testis in a cohort of men with NOA undergoing microdissection testicular sperm extraction (mTESE).we evaluated 276 patients, aged 37 (20-62) years, who underwent unilateral (86, 31.15%) or bilateral (190, 68.8%) mTESE from January 2018 through December 2021. During mTESE the entire surface of the testicular parenchyma was explored first in search for dilated seminiferous tubules: if no/ not enough sperm were retrieved, the deeper portion of the parenchyma was explored.Sperm were retrieved in 137 patients (49.6%). Histopathology demonstrated Sertoli-cell only syndrome in 65.6% of operated testes, while maturation arrest was found in 19.5%, hypospermatogenesis in 12.7% and hyalinosis in 2%. Sperm were obtained from the testis surface in 46 out of 276 patients (16.6%), and after a complete dissection in 91 subjects (32.9%). On multivariate logistic regression, only the histopathological subcategory hypospermatogenesis was predictive of the chance of retrieving sperm from the surface of the testis (OR 3.24, 95% CI 1.37-7.69, p = 0.007).most patients with NOA, particularly those with unfavorable histopathological patterns,, require a complete dissection of the testicular parenchyma to obtain enough good quality for ICSI.by enabling the complete exploration of the testicular parenchyma, mTESE is to be preferred to cTESE to retrieve sperm in patients with NOA. This article is protected by copyright. All rights reserved.

Introduction: The COVID-19 pandemic caused an increased mortality in nursing homes due to its quick spread and the age-related high lethality. Results: We observed a two-month mortality of 40%, compared to 6.4% in the previous year. This increase was seen in both COVID-19 positive (43%) and negative (24%) residents, but 8 patients among those testing negative on the swab, tested positive on serological tests. Increased mortality was associated with male gender, older age, no previous vitamin D supplementation and worse “activities of daily living (ADL)” scores, such as Barthel index, Tinetti scale and S.OS.I.A. classification. Conclusion: Our data confirms a higher geriatric mortality due to COVID-19. Negative residents also had higher mortality, which we suspect is secondary to preanalytical error and a low sensitivity of the swab test in poorly compliant subjects. Male gender, older age and low scores on ADL scales (probably due to immobility) are risk factors for COVID-19 related mortality. Finally, mortality was inversely associated with vitamin D supplementation. Design: In this observational study, we described the two-month mortality among the 157 residents (age 60-100) of a nursing home after Sars-CoV-2 spreading, reporting the factors associated with the outcome. We also compared the diagnostic tests for Sars-CoV-2.

Introduction: The endoscopic resection of large and bulky bladder cancers represents a challenge. To reduce the tumor and make it more easy to resect, we used neoadjuvant short and intensive intravesical mitomycin (MMC) therapy. Methods: Patients with large bladder tumors were evaluated for this study. At cystoscopy, the surgeon evaluated the feasibility of complete resection. In patients where this was not possible, biopsies from the tumor, bladder mucosa, and prostatic urethra were taken. These patients then underwent a short and intensive cytoreductive schedule of intravesical MMC. This was then followed by TUR-BT. Results: Fifteen patients were included in our study. The mean age was 74 years (range: 56–82; SD ±6 years). Mean tumor size was 51 mm (range: 35–65; SD ±8 mm). After neoadjuvant treatment, complete resection was then feasible in all patients. The mean tumor volume after the chemo-resection had reduced to 34 mm (range: 10–50; SD ±13 mm). No adverse effects were reported. Conclusion: Intravesical cytoreductive neoadjuvant MMC as an initial treatment of large NMIBC can be considered safe, effective, and feasible.

Whether to conduct remnant ablation or adjuvant radioactive iodine (RAI) therapy in patients with intrathyroidal differentiated thyroid carcinoma (DTC), sized 1.1–4 cm, is debated. We evaluated the impact of RAI on outcome in this category of DTCs. We retrospectively enrolled 308 patients submitted to total thyroidectomy: 198 had tumors sized 1.1–2 cm (Group 1) and 110 of 2.1–4 cm (Group 2). Both groups were divided into patients receiving and not receiving RAI after surgery. RAI+ and RAI− patients did not significantly differ, regarding several clinical and pathological features. Final outcome was defined according to dynamic risk stratification. Remission was observed in the majority of Group 1 and Group 2 patients and outcome did not significantly differ between RAI+ and RAI− patients: respectively, 95.8% vs. 93.7% in Group 1, and 87.7% vs. 86.5% in Group 2. The majority of persistent cases, either RAI+ or RAI−, received therapeutic RAI administration, and about 50% of RAI− cases had an excellent response at final follow up, whereas no RAI+ persistent patients had a beneficial effect. Our findings demonstrate that patients with an intrathyroidal DTC sized 1.1–4 cm do not benefit from RAI. The outcome of these patients remains favorable, and the few patients with persistent diseases can be treated with RAI during follow up.

Study question Is there any intra-surgical parameter able to predict the outcome of salvage microdissection testicular sperm extraction (mTESE) in patients with previous failed TESE? Summary answer Among all the variables under consideration, only the seminiferous tubules (ST) caliber pattern found at high magnification was able to significantly predict the mTESE outcome... What is known already Several studies have demonstrated that no clinical or hormonal parameters are able to predict the outcome of a salvage mTESE performed in patients with previous sperm retrieval failure (SRF). It has been previously demonstrated that a prediction model with the combination of two intra-surgical parameters such as the STs caliber, defined as dilated tubule (DT), slightly dilated tubules (SDT) and not dilated tubules (NDT), and testis histology had an excellent discrimination ability (AUC 0.93) to distinguish between cases with and without the outcome, but such prediction model has not been tested in patients undergoing salvage mTESE. Study design, size, duration A prediction model was built on a dataset of 63 patients, 29–50 years old, undergoing unilateral (15 ) or bilateral (48) salvage mTESE after failed TESE from 2015 through 2019, with a resulting N = 111 testes under consideration. Two models were compared, one with STs and histology as covariates, the other with STs alone: the second model was chosen due to better discrimination... Participants/materials, setting, methods we assessed internal validity with a bootstrapping procedure for a realistic estimate of the performance of the prediction model in similar future patients with NOA undergoing salvage mTESE. We repeated the entire modeling process in 259 samples drawn with replacement from the original sample, and determined the performances (AUC, sensitivity, specificity) of the selected prediction model. Calibration (correspondence between the predicted and observed probabilities) was visually assessed by inspecting the calibration belt... Main results and the role of chance Sperm retrieval was successful in 24 out of 63 patients (38%): age, testis volume and hormonal parameters did not vary among patients with successful sperm retrieval (SSR) or SRF. The prevalent histological pattern was Sertoli cell only syndrome (69.6%), while hypospermatogenesis, maturation arrest and hyalinosis were found in 4.5%, 23% and 1.8% of cases. The STs pattern was heterogeneous, with DTs being found only in 23.4% of testes. Sperm were found in 69% of DTs, 29% of SDTs, and 5% of NDTs. The prediction model correctly classified 82.88% of patients and explained the 26.5% variability of the outcome. The STs pattern significantly predicted the mTESE outcome with a sensitivity of 62% and a specificity of 90.2%, PPV 69.2%, NPV 87%. Both SDT (OR 0.105, 95% CI 0.034–0.317, p Limitations, reasons for caution The STs caliber pattern was subjectively evaluated at high magnification (24–36x) by comparing the individual ST appearance with the surrounding ones, however such evaluation was performed by the same experienced urologist with more than 1000 mTESE procedures performed to date. Wider implications of the findings: No clinical data but the STs appearance at high magnification could discriminate between patients with and without chances of SSR. These results reinforce the evidence supporting the superiority of mTESE compared to conventional TESE in retrieving sperm, particularly in lower prognosis patients with NOA such as those with previous SR. Trial registration number Not applicable

Study question Does the standard, not-dilated seminiferous tubules (STs) diameter vary according with different testis histology patterns in patients with non-obstructive azoospermia (NOA)? Summary answer The standard STs diameter differed significantly among cases with different testis histology: hypospermatogenesis (HYPO) had the highest STs diameter compared to the other histological subgroups. What is known already During microdissection testicular sperm extraction (mTESE), the identification of dilated STs, as subjectively evaluated at high magnification by comparing their apparent caliber with that of the surroundings, is crucial to identify residual foci of intact spermatogenesis and to retrieve sperm. Previous studies have demonstrated that dilated STs contain sperm in most cases, but it is not clear why in some cases an apparent normal tubular caliber does not correspond to spermatogenesis integrity. Aim of the present study was to assess whether different histology patterns could affect the STs diameter. Study design, size, duration We retrospectively evaluated 168 patients with NOA undergoing unilateral (N = 91) or bilateral (N = 77) mTESE from 2018 through 2019. One or more biopsy samples representative of the overall appearance of the testicular parenchyma were taken from one (for unilateral mTESE) or both testes (for bilateral mTESE), was fixed in Bouin’s solution and sent to the pathologist. Histological analysis was conducted by the same experienced pathologist, who examined at least 100 different tubule sections per biopsy sample. Participants/materials, setting, methods Each tubule section (N = 100 per sample) was evaluated at 10X magnification with a micrometer to measure the tubule diameter, then the mean ST diameter was computed. The basal membrane (BM) thickening was evaluated in every section, and a score was assigned by multiplying the degree of BM fibrosis (mild=1, moderate=2, severe=3) for the number of sections (e.g. BM score for moderate fibrosis in 50 sections=2x50=100). Leydig cells hyperplasia (LCH), if present, was also annotated. Main results and the role of chance The median + interquartile range STs diameter was 140; 110–185 mm, while the median BM score was 100; 10–150. Sertoli cell only syndrome (SCO) was found in 51.1% of cases, focal SCO (FSCO) in 4,7%, early (EMA) and late (LMA) maturation arrest in 10.2 and 2.73% respectively, HYPO in 26.17% and hyalinosis (HL) in 5% of cases. LCH was found in 46.88% of samples. STs diameter, BM score and LCH differed significantly among the different histological patterns: STs diameter was 125; 100–148 in SCO, 162; 102–187 in FSCO, 130; 100–175 in EMA, 145; 130–195 in LMA, 205; 170–240 in HYPO and 57.5; 42.5–100 in HL. HYPO samples also had the lowest BM score (20;1–100; p Limitations, reasons for caution The STs were carefully cut before extraction in order to preserve their structural integrity, however the accuracy of such a method of estimating the STs diameter needs to be assessed by further studies. Wider implications of the findings: The identification of dilated STs remains the best strategy to retrieve sperm by mTESE, since larger STs diameters are mostly associated with the more favorable histological patterns. However, dilated STs may be also found in cases with LMA, which explains why in some cases dilated STs do not contain sper. Trial registration number Not applicable

BACKGROUND Patients with non-obstructive azoospermia with a previously failed conventional testicular sperm extraction may undergo a salvage microdissection testicular sperm extraction with the probability of successful sperm retrieval being almost dependent upon the number of previous surgical attempts and to different histopathologic categories. OBJECTIVES To determine whether the seminiferous tubules pattern and the histological categories could affect the sperm retrieval rate in patients with non-obstructive azoospermia undergoing salvage microdissection testicular sperm extraction after failed conventional testicular sperm extraction. MATERIALS AND METHODS Seventy-nine patients undergoing unilateral or bilateral salvage microdissection testicular sperm extraction were evaluated. During microdissection testicular sperm extraction, if present, dilated tubules were retrieved, otherwise, tubules with slightly larger caliber than that of the surroundings were removed. When no dilated tubule or tubule with slightly larger caliber was found, not dilated tubules were excised. A prediction model was built with seminiferous tubules pattern and testis histology as covariates. RESULTS Sperm retrieval was successful in 30 out of 79 patients. The prediction model correctly classified 88.3% of cases, explained the 29.7% variability of the outcome, and significantly predicted the microdissection testicular sperm extraction outcome with a sensitivity of 67.7% and a specificity of 90.2%, Both tubules with slightly larger caliber and not dilated tubules were negatively associated with the chance of retrieving spermatozoa. Among the histological categories, only early maturation arrest was significant to the model (log(SSR) = 0.57 - 1.9SDT - 3.3NDT - 1.76EMA) (where SSR is sperm retrieval rate, SDT is tubule with slightly larger caliber, NDT is not dilated tubule, and EMA is early maturation arrest). The model had a clearly useful discrimination (area under the curve = 0.814), the estimated performance was 0.8105, and internal calibration was acceptable (p > 0.05). DISCUSSION Seminiferous tubules pattern and testis histology may reliably explain the salvage microdissection testicular sperm extraction outcome in all patients with non-obstructive azoospermia apart from those with early maturation arrest, where the homogeneous apparent seminiferous tubules pattern may be misleading. CONCLUSION The outcome of salvage microdissection testicular sperm extraction can be predicted by the same intrasurgical parameters that have been demonstrated to predict the outcome of microdissection testicular sperm extraction in naive patients with non-obstructive azoospermia.

Cytology is the gold standard method for the differential diagnosis of thyroid nodules, though 25–30% of them are classified as indeterminate. We aimed to set up a ‘thyroid risk score’ (TRS) to increase the diagnostic accuracy in these cases. We prospectively tested 135 indeterminate thyroid nodules. The pre-surgical TRS derived from the sum of the scores assigned at cytology, EU-TIRADS classification, nodule measurement, and molecular characterization, which was done by our PTC-MA assay, a customized array able to cost-effectively evaluate 24 different genetic alterations including point mutations and gene fusions. The risk of malignancy (ROM) increased paralleling the score: in the category >4 and ≤ 6 (low suspicion), >6 ≤ 8 (intermediate suspicion), and >8 (high suspicion); ROM was 10, 47 and 100%, respectively. ROC curves selected the score >6.5 as the best threshold to differentiate between malignant and benign nodules (P < 0.001). The TRS > 6.5 had a better performance than the single parameters evaluated separately, with an accuracy of 77 and 82% upon inclusion of noninvasive follicular thyroid neoplasm with papillary-like nuclear features among malignant or benign cases, respectively. In conclusion, for the first time, we generated a score combining a cost-effective molecular assay with already validated tools, harboring different specificities and sensitivities, for the differential diagnosis of indeterminate nodules. The combination of different parameters reduced the number of false negatives inherent to each classification system. The TRS > 6.5 was highly suggestive for malignancy and retained a high accuracy in the identification of patients to be submitted to surgery.

PURPOSE: The present prediction model was intended to verify whether serum FSH level could be predictive of testis histology in patients with non-obstructive azoospermia (NOA). METHODS: We evaluated two datasets of patients with NOA: the first (San Paolo dataset) comprising 558 patients, 18–63 years old, the second (Procrea dataset) composed by 143 patients, 26–62 years old; bot datasets were combined to obtain a validation set. Multinomial logistic regression was first run with serum FSH and testis volume as independent predictors of testis histology, then, the correctly classified histological subcategories were set as outcome variables of a prediction model in both development and validation sets. RESULTS: Multinomial logistic regression showed that FSH was a significant predictor of testis histology in 58% of cases, although it was unable to correctly classify cases with focal SCO or maturation arrest (MA). A prediction model was then run with hypospermatogenesis (HYPO) and Sertoli-only syndrome (SCO) as outcome variables of a binary logistic regression. FSH significantly predicted both HYPO and SCO, with a sensitivity of 40.9 and 80.7 and a specificity of 84.3 and 46.8 respectively. The model showed a fair discriminative ability (ROC AUC 0.705 and 0.709 respectively) and was adequately calibrated. CONCLUSIONS: Supported by a robust statistical analysis, we conclude that serum FSH level cannot be considered a prognostic marker of spermatogenic dysfunction in patients with NOA ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10815-019-01613-8) contains supplementary material, which is available to authorized users.

BACKGROUND microTESE proved to be the gold standard surgical approach for patients with non-obstructive azoospermia (NOA), but sperm retrieval rates (SRRs) vary considerably among centers. Some authors compared their SRRs with the pattern of seminiferous tubule caliber found at high magnification, but none provided diagnostic accuracy measures. OBJECTIVE The present retrospective study sought to verify the diagnostic accuracy of the pattern of seminiferous tubule caliber in predicting the sperm retrieval in NOA patients. MATERIALS AND METHODS Data from 143 infertile NOA men undergoing unilateral (64) or bilateral (79) microTESE (222 testes) were retrospectively evaluated. During microTESE, if present, dilated tubules (DTs) were retrieved, otherwise tubules with slightly larger caliber (SDT) (×24) than that of the surroundings were removed. When no DT or SDT were found, not dilated tubules (NDTs) were excised. RESULTS Spermatozoa were retrieved in 95 of 222 testes (42.8%); sperm retrieval was successful in 90% of testes with DTs, in 47% of those with SDTs, and only in 7% of those with NDTs (p

The present study sought to determine the diagnostic accuracy of FSH level, testicular volume, and testicular histology in predicting the successful sperm retrieval (SSR) in a large cohort of patients with non-obstructive azoospermia undergoing conventional testicular sperm extraction (TESE).We retrospectively evaluated 356 patients with non-obstructive azoospermia between June 2004 and July 2009. Binary logistic regression was used to evaluate the diagnostic accuracy of our predicting model, identifying sperm retrieval rate as binary dependent variable. The predictive accuracy of all variables individually evaluated was quantified with area under curve (AUC) estimates derived from receiver operating characteristic (ROC) curve.The mean patients' age was 36.8 years. Testicular sperm were retrieved in 158 out of 356 patients (44.3 %). Histological diagnosis of Sertoli cell only syndrome (SCO) was obtained in 216 patients (60.6 %), while 55 patients (15.4 %) had maturation arrest (MA) and 85 (23.8 %) had hypospermatogenesis (HYPO). The binary logistic regression model was statistically significant (χ

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.