A proposed mathematical model to help preoperative planning between RIRS and MiniPerc for renal stones between 10 and 20 mm using holmium:Yag laser (Cyber Ho): the stone management according to size-hardness (SMASH) score.

To evaluate the performance of a mathematical model to drive preoperative planning between RIRS and MiniPerc (MP) for the treatment of renal stones between 10 and 20 mm. Patients with a renal stone between 10 and 20 mm were enrolled. A mathematical model named Stone Management According to Size-Hardness (SMASH) score was calculated: hounsfield units (HU) χ stone maximum size (cm)/100. Patients were divided into 4 groups: RIRS with score < 15 (Group A), RIRS with score ≥ 15 (Group B), MP with score < 15 (Group C), MP with score ≥ 15 (Group D). Cyber Ho device was always used. Stone free rate (SFR) was assessed after 3 months. Complication rate and need for auxiliary procedures were evaluated. Between January 2019 and December 2021, 350 patients were enrolled (87, 88, 82 and 93 in Groups A, B, C and D). Mean stone size was 13.1 vs 13.3 mm in Group A vs B (p = 0.18) and 16.2 vs 18.1 mm in Group C vs D (p = 0.12). SFR was 82%, 61%, 75% and 85% for Groups A, B, C and D. SFR was comparable between Groups C and D (p = 0.32) and Groups A and C (p = 0.22). SFR was significantly higher in Group A over B (p = 0.03) and in Group D over B (p = 0.02). Complication rate was 2.2%, 3.4%, 12.1%, 12.9% for Groups A, B, C, D. RIRS and MP are both safe and effective. The mathematical model with the proposed cut-off allowed a proper allocation of patients between endoscopic and percutaneous approaches.Registration number of the study ISRCTN55546280.

A comparison between vapor tunnel and virtual basket for the treatment of proximal ureteral stones using holmium:YAG laser (Cyber Ho): which is the best tool to reduce retropulsion?

PURPOSE: To compare vapor tunnel (VT) and virtual basket (VB) tools to reduce retropulsion in the treatment of proximal ureteral stones. METHODS: Patients with a single proximal ureteral stone were randomly assigned to holmium laser lithotripsy with the use of VT (Group A) or VB (Group B) tool. The 150W holmium:YAG cyber Ho generator was used. We compared operative time, dusting time, need for flexible ureteroscopy due to stone push-up and occurrence of ureteral lesions. The stone-free rate (SFR) and the occurrence of postoperative ureteral strictures were assessed. RESULTS: 186 patients were treated, of which 92 with the VT (49.5%, Group A) and 94 with the VB (50.5%, Group B). Mean stone size was 0.92 vs. 0.91 cm in Groups A vs. B (p = 0.32). Mean total operative time and dusting time were comparable between groups. 7 (7.6%) vs. 6 (6.4%) patients in Groups A vs. B required a flexible ureteroscope because of stone push-up (p = 0.12). Ureteral mucosa lesions were observed in 15 (16.3%) vs. 18 (19.1%) cases in the VT vs. VB group (p = 0.09). 1-Month SFR was comparable (97.8% vs. 95.7%, p = 0.41). We observed one case (1.1%) of postoperative ureteral stricture in the VT group vs. two cases (2.1%) in the VB group (p = 0.19). CONCLUSIONS: VT and VB are equally safe and effective tools in reducing retropulsion of ureteral stones. Operative time, dusting time and SFR were comparable. They also equally avoided stone push-up and prevented ureteral lesions, which may later occur in ureteral strictures.

Evaluation of the learning curve for Thulium laser enucleation of the prostate in a contemporary cohort.

PURPOSE: To assess the learning curve of Thulium laser enucleation of the prostate (ThuLEP) of a single surgeon. METHODS: Hundred patients suffering from benign prostatic hyperplasia were treated by the same surgeon. In all cases, a well-trained urologist was present in the operating room. Patients urinary function was assessed preoperatively using the International Prostate Symptoms Score (IPSS), maximum flow rate and Post-Void Residual volume. Preoperative prostate volume was recorded. Enucleation and morcellation efficiency and complication rate were evaluated. Patients were divided into 5 cohorts of 20 consecutive cases to assess changes in outcomes through time. RESULTS: Mean age of patients was 73.1 years (SD 17.5) and mean prostate volume was 89.7 ml (SD 55.1). Overall, mean enucleation and morcellation efficiency were 1.7 (SD 2.9) and 5.1 (SD 2.7) g/min. A statistically significant increase in enucleation efficiency was observed when comparing cohort 1 vs 2 (0.9 vs 1.3 g/min, p = 0.03) and cohort 2 vs 3 (1.3 vs 1.7 g/min, p = 0.02). A statistically significant increase in morcellation efficiency was observed when comparing cohort 1 vs 2 (2.8 vs 3.7 g/min, p = 0.02) and cohort 2 vs 3 (3.7 vs 4.9 g/min, p = 0.03). In both cases, no significant differences were observed when comparing the following cohorts. Complication rate showed no significant differences throughout the caseload. CONCLUSIONS: In our single-surgeon experience, we observed a learning curve of nearly 60 cases for the ThuLEP procedure in presence of a well-trained surgeon. Complication rate was low from the beginning of surgical experience.

Pulsed-wave vs Continuous-wave Thulium Fiber Laser Enucleation of the Prostate (ThuFLEP): A Comparison of Perioperative Outcomes.

OBJECTIVE: To compare intra and early postoperative outcomes between pulsed-wave and continuous-wave Thulium Fiber Laser Enucleation of the Prostate (PW-ThuFLEP vs CW-ThuFLEP) for the treatment of benign prostatic hyperplasia. METHODS: 238 patients with lower urinary tract symptoms due to benign prostatic hyperplasia underwent PW-ThuFLEP (118 patients) vs CW-ThuFLEP (120 patients). Preoperative prostate volume, adenoma volume, prostate-specific antigen (PSA), and hemoglobin values were recorded. International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual volume, and International Index of Erectile Function-5 score (IIEF-5) were assessed. Operative time, enucleation time, enucleation efficiency, catheterization time, irrigation volume, hospital stay, hemoglobin drop, and postoperative complications were recorded. Micturition improvements and sexual outcomes were evaluated 3months after surgery. RESULTS: CW-ThuFLEP showed shorter operative time (61.5 vs 67.4 minutes, P = .04). Enucleation time (50.2 vs 53.3 minutes, P = .12), enucleation efficiency (0.8 vs 0.7 g/min, P = .38), catheterization time (2.2 vs 2.1days, P = .29), irrigation volume (32.9 vs 32.8L, P = .71), hospital stay (2.8 vs 2.6days, P = .29) and hemoglobin drop (0.38 vs 0.39 g/dL, P = .53) were comparable. No significant difference in complication rate was observed. At 3-month follow-up, the procedures did not show any significant difference in IPSS, Qmax, post-void residual volume, IIEF-5, and PSA value. CONCLUSION: PW-ThuFLEP and CW-ThuFLEP both relieve lower urinary tract symptoms equally, with high efficacy and safety. Operative time was significantly shorter with CW-ThuFLEP, but with a small difference with low clinical impact. Enucleation time, enucleation efficiency, catheterization time, irrigation volume, hospital stay, hemoglobin and PSA drop, complication rate, and sexual outcomes showed no differences.

Quantitative ultrasound and DXA measurements in aromatase inhibitor-treated breast cancer women receiving denosumab.

PURPOSE: Denosumab has been proven to reduce fracture risk in breast cancer (BC) women under aromatase inhibitors (AIs). Quantitative ultrasound (QUS) provides information on the structure and elastic properties of bone. Our aim was to assess bone health by phalangeal QUS and by dual-energy X-ray absorptiometry (DXA), and to evaluate bone turnover in AIs-treated BC women receiving denosumab. METHODS: 35 Postmenopausal BC women on AIs were recruited (mean age 61.2 ± 4.5 years) and treated with denosumab 60 mg administered subcutaneously every 6 months. Phalangeal QUS parameters [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), Bone Transmission Time (BTT)] and DXA at lumbar spine and femoral neck were performed. Serum C-telopeptide of type 1 collagen (CTX) and bone-specific alkaline phosphatase (BSAP) were also measured. The main outcomes were compared with a control group not receiving denosumab (n = 39). RESULTS: In patients treated with denosumab, differently from controls, QUS and DXA measurements improved after 24 months, and a reduction of CTX and BSAP was detected at 12 and 24 months in comparison to baseline (P < 0.05). The percent changes (Δ) of QUS measurements were significantly associated with ΔBMD at femoral neck, and ΔCTX and ΔBSAP were associated with ΔBMD at lumbar spine (r = -0.39, P = 0.02; r = -0.49, P = 0.01, respectively). CONCLUSIONS: Denosumab preserves bone health as assessed by phalangeal QUS and DXA. Since inexpensive and radiation-free, phalangeal QUS may be considered in the follow-up of AIs-treated BC women receiving denosumab.

Vitamin D and bone mineral density changes in postmenopausal women treated with strontium ranelate.

OBJECTIVE: Vitamin D deficiency is widespread and often reported in subjects treated for osteoporosis. Optimal vitamin D repletion was previously shown to maximize the efficacy of anti-resorptive agents. To date, no information exists about the role of vitamin D in the response to strontium ranelate (SrR) treatment. The aim of our study was to investigate the BMD response to SrR in accordance with change of vitamin D status. METHODS: A retrospective analysis of 108 women receiving SrR for postmenopausal osteoporosis was carried out. Women were treated with SrR (2 g/day), with cholecalciferol (25,000 IU biweekly) and calcium carbonate as appropriate. Lumbar spine and femoral neck BMD, bone formation markers (BGP, ALP), resorption marker (OH-PRO) and serum 25(OH)D were measured at baseline after 18-months. All participants were divided into two groups according to the median variation of 25(OH)D over the observation period. RESULTS: SrR was associated with improvement of BMD at lumbar spine (p < 0.0001) and to a non significant variation at femoral neck (p = 0.2). Only subjects with Δ25(OH)D > 6.14 %, reported a significant BMD gain at femoral neck (p = 0.03). Change of BMD at femoral neck was positively associated with modification of ALP (r = 0.28, p = 0.01). This association was not maintained when considering only women with Δ25(OH)D < 6.14 % (r = 0.28, p = 0.09). At a multiple regression analysis, ALP change was the only predictor of femoral neck BMD modification (ß 0.13; SE 0.05; p = 0.01). CONCLUSION: Improvement of vitamin D status was associated with enhancement of BMD response to SrR in women with postmenopausal osteoporosis, in particular, at femoral neck.

The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for association from a meta-analysis in individuals of European ancestry.

BACKGROUND/AIMS: The development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D. Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. METHODS: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448). RESULTS: Variability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89-1.04) or in the meta-analysis (OR = 1.01; 0.98-1.05). CONCLUSION: Our data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

The ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism modulates the beneficial effect of weight loss on fasting glucose in non-diabetic individuals.

BACKGROUND AND AIMS: Several studies have reported that the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism (rs1044498) interacts with increased adiposity in affecting glucose homeostasis and insulin sensitivity. Conversely, one would expect that the amelioration of glucose homeostasis observed after weight loss is modulated by the ENPP1 K121Q polymorphism. The aim of our study was to test such hypothesis, in non-diabetic overweight-obese individuals. METHODS AND RESULTS: Two hundred eleven non-diabetic overweight-obese individuals were studied. Body mass index (BMI), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR index) and lipid levels were obtained before and after 6-week lifestyle intervention (LI; diet and exercise) and their changes calculated as baseline minus 6-week values. LI decreased BMI, glucose, HOMA-IR and triglyceride levels (p < 0.001 for all). No difference across genotype groups (160 KK and 51 KQ or QQ - named as XQ - individuals) was observed in these changes. In a multivariate model, BMI changes predicted fasting glucose changes (ß = 0.139 mmol/L (2.50 mg/dl) for 1 unit BMI change, p = 0.005). This correlation was not significant among KK individuals (ß = 0.082; p = 0.15), while much steeper and highly significant among XQ individuals (ß = 0.336; p = 0.00008) (p-value for Q121-by-weight loss interaction = 0.047). CONCLUSION: Individuals carrying the ENPP1 Q121 variant are highly responsive to the effect of weight loss on fasting glucose. This reinforces the previously suggested hypothesis that the Q121 variant interacts with adiposity in modulating glucose homeostasis.

Brand-dependent volatile fingerprinting of Italian wines from Valpolicella.

Head-space solid-phase microextraction (HS-SPME) coupled to gas-chromatography-mass spectrometry was developed and applied to obtain the volatile aromatic fingerprints of three typical Italian wines, Valpolicella, Amarone and Recioto, all produced in the restricted geographical area of Valpolicella (Veneto, Italy) with the same grape cultivars within the regulations of a rigid disciplinary of production. Differences between the three typologies are mainly linked to the different withering times to which grapes are subjected before vinification, which strongly influences the concentration and the development of volatile aroma compounds. A total of 22 different wines (7 Valpolicella, 10 Amarone and 5 Recioto) were characterised in terms of aromatic volatile profile with the aim to distinguish the different products and to evaluate the possibility to differentiate the same product from different brands. For the chemometric evaluation of the data one-way analysis of variance (ANOVA), principal component analysis (PCA) and hierarchical cluster analysis (HCA) were tested. All the chemometric tools employed allow to differentiate between the three products. More intriguing is the ability of the chemometric approach to differentiate between the same product (Amarone, Recioto) from different winery, thus showing the potential of this approach to characterize the brand-dependent typicality of wines, which is usually related to subtle technological differences which nevertheless have strong influences on the organoleptic characteristics of the products.

TRIB3 R84 variant affects glucose homeostasis by altering the interplay between insulin sensitivity and secretion.

AIMS/HYPOTHESIS: The results of studies on the genetics of complex traits need to be replicated and to reach robust statistical significance before they can be considered as established. We here tried to replicate the previously reported association between the TRIB3 Q84R polymorphism (rs2295490) and glucose homeostasis. METHODS: Three samples of Europeans with fasting glucose <7.0 mmol/l were studied. In sample 1 (n=791), the association between TRIB3 Q84R and impaired glucose regulation (IGR; defined as impaired fasting glucose and/or impaired glucose tolerance and/or type 2 diabetes by OGTT) and insulin sensitivity (ISI), and its interplay with early-phase insulin secretion (i.e. disposition index [DI]) were analysed. Sample 2 (n=374) and sample 3 (n=394) were used to replicate the association with IGR and insulin sensitivity (by glucose clamp), respectively. Genotyping was performed by TaqMan allele discrimination. RESULTS: R84 carriers were at higher risk of IGR: OR for the additive model 1.54, p=0.004, and 1.63, p=0.027, in samples 1 and 2, respectively. In sample 1, both ISI (p=0.005) and DI (p=0.043) were progressively lower from QQ to QR and RR individuals. A 'triangulation approach' indicated that the association with IGR was mostly mediated by DI rather than by ISI changes (i.e. being the expected ORs 1.51 and 1.25, respectively). In sample 3, glucose disposal was 38.8+/-17.7, 33.8+/-14.4, and 31.6+/-13.3 micromol min(-1)kg(-1), p=0.022, in QQ, QR and RR individuals, respectively. CONCLUSIONS/INTERPRETATION: Our data confirm that the TRIB3 R84 variant affects glucose homeostasis and suggest this effect is due to an alteration of the interplay between insulin sensitivity and secretion.

Metabolic syndrome and erectile dysfunction among obese non-diabetic subjects.

OBJECTIVE: To investigate whether MS is associated with erectile dysfunction (ED) among obese non diabetic individuals. METHODS: A cross-sectional study was carried out to examine the association between the cluster of abnormalities related to the MS and ED as evaluated by the International Index of Erectile Function (IIEF). Fifty consecutive obese [i.e. body mass index (BMI) > or =30 kg/m2], nondiabetic whites (age 42.1+/-11.3 yr, BMI 43.3+/-8.7 kg/m2) were recruited. RESULTS: The prevalence of MS as well as that of any MS component were not different between subjects with or without ED. Neither the prevalence of ED (34.3% vs 33.4%, p=0.6), nor IIEF score (21.5+/-3.9 vs 21.7+/-3.7, p=0.8), were different between patients with or without MS. IIEF was similar across subgroups of individuals stratified according to the number of MS components and was not related to HOMAIR index. Hypogonadism was observed in 30.8% and 28.1% individuals with and without MS (p=0.58). Testosterone and BMI levels were inversely related (r=-0.3, p=0.04). CONCLUSION: Among obese non-diabetic individuals the risk of developing ED is independent of the presence of MS factors. Testosterone levels progressively decrease with increasing body weight.

IRS1 G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of 'low-frequency-low-risk' variants.

AIMS/HYPOTHESIS: The aim of the study was to determine the association between IRS1 G972R polymorphism and type 2 diabetes; published data concerning this association have been conflicting. To obtain further insight into this topic, we performed a meta-analysis of all available case-control studies. METHODS: We performed a meta-analysis of 32 studies (12,076 cases and 11,285 controls). RESULTS: The relatively infrequent R972 variant was not significantly associated with type 2 diabetes (OR 1.09, 95% CI 0.96-1.23, p = 0.184 under a dominant model). Some evidence of heterogeneity was observed across studies (p = 0.1). In the 14 studies (9,713 individuals) in which the mean age at type 2 diabetes diagnosis was available, this variable explained 52% of the heterogeneity (p = 0.03). When these studies were subdivided into tertiles of mean age at diagnosis, the OR for diabetes was 1.48 (95% CI 1.17-1.87), 1.22 (95% CI 0.97-1.53) and 0.88 (95% CI 0.68-1.13) in the youngest, intermediate and oldest tertile, respectively (p = 0.0022 for trend of ORs). CONCLUSIONS/INTERPRETATION: Our findings illustrate the difficulties of ascertaining the contribution of 'low-frequency-low-risk' variants to type 2 diabetes susceptibility. In the specific context of the R972 variant, approximately 200,000 study individuals would be needed to have 80% power to identify a 9% increase in diabetes risk at a genome-wide significance level. Under these circumstances, a strategy aimed at improving outcome definition and decreasing its heterogeneity may critically enhance our ability to detect genetic effects, thereby decreasing the required sample size. Our data suggest that focusing on early-onset diabetes, which is characterised by a stronger genetic background, may be part of such a strategy.

Disappearance of a virilizing adrenal tumor following therapy with cyproterone acetate.

A 57-year-old woman presented with an apparently obvious diagnosis of iatrogenic virilization. At the age of 51, she began a 4-year treatment with prednisone or cyclosporine, which are known to promote hair growth, for Behçet disease. At the age of 56, osteoporosis was overtreated with the anabolic steroid nandrolone. Insignificant inhibition by dexamethasone of the extremely high serum concentrations of testosterone and less high concentrations of weak androgens prompted us to search for a virilizing tumor. Computed tomography showed a 2.3 x 1.5 cm nodule in the right adrenal gland. As the patient refused surgery, virilization was treated with the antiandrogen cyproterone acetate (CPA), but for only 4 months because clinical and hormone abnormalities reversed and the tumor was no longer visible. The patient remains symptom-free. This first report of a curative effect of CPA on a purely virilizing adrenal tumor opens new avenues in the management of such tumors.

Preliminary data suggest that mutations in the CgRP pathway are not involved in human sporadic cryptorchidism.

In testicular descent to the scrotum, a multistep process, many anatomical and hormonal factors play a role. Cryptorchidism occurs in about 1-2% of males and may cause secondary degeneration of the testes. Animal models have shown that abnormalities, in the calcitonin gene-related peptide (CgRP) activity, could be relevant in the pathogenesis of cryptorchidism. We performed a mutation screening by PCR exon amplification, single-strand conformation polymorphism (SSCP) and sequencing in four candidate genes, CgRPs (alphaCgRP, betaCgRP), their receptor (CgRPR) and the receptor component protein (CgRP-RCP), in 90 selected cases of idiopathic unilateral or bilateral cryptorchidism. Mutation screening of the coding regions and intron-exon boundaries revealed some polymorphic variants but no pathogenic sequence changes. These preliminary data suggest that these genes are not major factors for cryptorchidism in humans.

Long-term hemostatic effects of cholesterol-lowering therapy with atorvastatin.

This study assessed hemostatic effects of an HMC-CoA reductase inhibitor, atorvastatin, on different parameters in 32 hypercholesterolemic patients of both sexes. In the patients and in 25 control subjects, plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor (PAI-1), D-dimer, prothrombin fragment 1 + 2 (F1 + 2), total cholesterol, triglycerides and fibrinogen had been measured. All these parameters were evaluated in patients after 6 and 12 months of treatment with atorvastatin at a dosage of 20 mg/day. This treatment significantly lowered the total cholesterol level in all patients. Moreover, after 6 months of atorvastatin treatment, PAI-1 and F1 + 2, which were both increased at baseline, were significantly reduced. This reduction continued after 12 months. The present results show that a reduction of hemostatic abnormalities, which exist in hypercholesterolemia, may be another important effect of the atorvastatin therapy.

Metabolic effects of dehydroepiandrosterone replacement therapy in postmenopausal women.

OBJECTIVE: To investigate whether long-term treatment with dehydroepiandrosterone (DHEA) in postmenopausal women can modify insulin sensitivity and plasma lipid profile. DESIGN AND METHODS: Twenty healthy postmenopausal women with serum dehydroepiandrosterone sulfate (DHEA-S) concentrations <2.5 micromol/l were enrolled and randomly assigned to two different treatment groups: group 1 were treated with micronized DHEA, 25 mg/day at 0800 h for 12 months; group 2 were treated with an identical placebo tablet. At the beginning and at the end of the study, plasma lipid profile, glucose tolerance (oral glucose tolerance test) and insulin sensitivity (euglycemic hyperinsulinemic clamp: M index) were assessed. RESULTS: After 12 months, the group treated with DHEA showed a considerable improvement of insulin sensitivity (M index +29.55%, P=0.01) and lipid pattern (high-density lipoprotein cholesterol +11.61%, P=0.03; low-density lipoprotein cholesterol -11.07%, P=0.04; triglycerides -19.60%, P=0.03), but glucose tolerance did not change. No modifications were observed in the placebo group. CONCLUSIONS: Long-term treatment with DHEA ameliorates some metabolic parameters that are linked to increased cardiovascular risk and, consequently, this seems to be an interesting therapeutic tool in the management of the postmenopausal syndrome.