Abstract Background It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health. Objective To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers. Design, setting, and participants 29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months. Intervention All patients underwent degarelix administration. Outcome measurements and statistical analysis T -test or sign test and Pearson or Spearman test for continuous variables were used when indicated. Results and limitations Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to − 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation. Conclusions an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.
Tidal effects related to the traversability across thin shells are examined in spherically symmetric geometries. We focus mainly on shells separating inner from outer regions of gravastars (de Sitter -- i.e., $\Lambda>0$ -- interior and Schwarzschild exterior of mass parameter $M$), but we also examine other related geometries by including the possibility of a negative cosmological constant and, besides, non trivial topologies where the shell separates two outer regions. The analysis is developed for radially traversing objects and for tides in both radial and transverse directions, which present difficulties of somewhat different nature. Transverse tides are unavoidable across shells which satisfy the flare-out condition, while shells in trivial topologies, i.e. geometries with one asymptotic region, are more indulgent with the issue of insurmountable tides. Besides, contradicting other cases analyzed in previous works, we find that large radial tides cannot be avoided when traveling across the shell in the gravastar solution, but in non-trivial topologies they can. We study with special attention the traversability in practice of the transition layer in the thin-shell gravastar solution. In particular, a finite object which traverses radially the shell in a gravastar with $\sqrt{\Lambda}\ll 1/M$ undergoes a compression effect in both the transverse and the radial directions due to the tides associated to the thin layer. The results are interpreted in terms of the total momentum transfer obtained by integrating the travel time of the object.
Introduction: Diabetes is the most common cause of chronic kidney disease (CKD). For patients with diabetes and CKD, the underlying cause of their kidney disease is often assumed to be a consequence of their diabetes. Without histopathological confirmation, however, the underlying cause of their disease is unclear. Recent studies have shown that next-generation sequencing (NGS) provides a promising avenue toward uncovering and establishing precise genetic diagnoses in various forms of kidney disease. Methods: Here, we set out to investigate the genetic basis of disease in nondiabetic kidney disease (NDKD) and diabetic kidney disease (DKD) patients by performing targeted NGS using a custom panel comprising 345 kidney disease-related genes. Results: Our analysis identified rare diagnostic variants based on ACMG-AMP guidelines that were consistent with the clinical diagnosis of 19% of the NDKD patients included in this study. Similarly, 22% of DKD patients were found to carry rare pathogenic/likely pathogenic variants in kidney disease-related genes included on our panel. Genetic variants suggestive of NDKD were detected in 3% of the diabetic patients included in this study. Discussion/Conclusion: Our findings suggest that rare variants in kidney disease-related genes in a diabetic background may play a role in the pathogenesis of DKD and NDKD in patients with diabetes.
For non-muscle-invasive bladder cancer (NMIBC) requiring radical surgery, limited data are available comparing robotic-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) to open radical cystectomy (ORC). The objective of this study was to compare the two surgical techniques.A multicentric cohort of 593 patients with NMIBC undergoing iRARC or ORC between 2015 and 2020 was prospectively gathered. Perioperative and pathologic outcomes were compared.A total of 143 patients operated on via iRARC were matched to 143 ORC patients. Operative time was longer in the iRARC group (p = 0.034). Blood loss was higher in the ORC group (p < 0.001), with a consequent increased post-operative transfusion rate in the ORC group (p = 0.003). Length of stay was longer in the ORC group (p = 0.007). Post-operative complications did not differ significantly (all p > 0.05). DFS at 60 months was 55.9% in ORC and 75.2% in iRARC with a statistically significant difference (p = 0.033) found in the univariate analysis.We found that iRARC for patients with NMIBC is safe, associated with a lower blood loss, a lower transfusion rate and a shorter hospital stay compared to ORC. Complication rates were similar. No significant differences in survival analyses emerged across the two techniques.
data that hypovitaminosis D is a reliable prognostic parameter or that the outcome of patients with PC might be improved by vitamin D supplementation. Several drawbacks hamper the clinical interpretation of serum vitamin D levels in cancer: the hormonal activity of vitamin D is mediated by its binding to vitamin D receptor (VDR) within the cell nuclei, and both VDR expression and VDR polymorphisms reflect the individual susceptibility to vitamin D action 3 ; and hypovitaminosis D is associated with secondary hyperparathyroidism, which could have contributed tothe negative prognostic features observed. Parathyroid hormone (PTH), in fact, is similar to PT-related peptide, which is a potent growth factor, and both PTH and PT-related peptide interact with the same receptor that is expressed by PC cells. 4 In the study by Nyame et al, 1 neither tissue VDR and its relevant polymorphisms nor serum PTH were measured; therefore, information on the interaction between vitamin D status and these important biologic parameters is lacking. Moreover, the assays to determine serum vitamin D levels are not standardized, and a significant variability among methods and laboratories was reported. 5 This further complicates the application of the results of the Nyame et al 1 study to clinical practice. In their discussion, Nyame et al 1 stated that patients with PC with intermediate risk may benefit, in terms of disease outcome, from the normalization of vitamin D levels. In principle, we agree with the authors that future studies are warranted to assess the efficacyofvitaminD supplementationin terms ofPC aggressiveness. However, caution should be taken in administering vitamin D to patients with PC outside a clinical trial. In fact, the results of a prospective phase III clinical trial testing the efficacy of high-dose calcitriol plus docetaxel versus single-agent docetaxel in men with castrate-resistant metastatic PC showed a shorter survival in the vitamin D arm compared with the control arm. 6
The Renal Artery Aneurysm (RAA) is a relatively uncommon vascular lesion. A renal artery disease coexisting in patients with Renal Cell Carcinoma (RCC) is an even more infrequent clinical presentation. We reported on the treatment of a rare case of incidentally intraoperative renal artery aneurysm discovered during a nephron-sparing surgery for RCC. After the surgery the patient did not need hypertension therapy any longer. This event is well-known, in fact a number of possible contributions to a renin-mediated hypertension management has been postulated.
Background: Conditional survival (CS) may reveal important differences in cancer-specific mortality (CSM) among patients with nonmetastatic renal cell carcinoma (nmRCC). This study assessed CS according to T and N stages in patients treated surgically for nmRCC. Patients and Methods: Within the SEER database (2001–2015), all patients with nmRCC treated with either partial or radical nephrectomy were identified. CSM-free estimates according to T and N stage and substage groupings (pT1aN0–pT4N0 and pTanyN1) and multivariable Cox regression models with adjustment for Fuhrman grade and histologic subtype were assessed. Results: According to T and N stage and substage groupings, the following patients were included in the study: 35,966 (46.2%) with pT1aN0 disease; 18,858 (24.2%) with pT1bN0; 5,977 (7.7%) with pT2aN0; 2,511 (3.2%) with pT2bN0; 11,839 (15.2%) with pT3aN0; 1,037 (1.3%) with pT3b–cN0; 402 (0.5%) with pT4N0; and 1,302 (1.7%) with pTanyN1. Conditional CSM-free survival estimates were 98.2% at 1 year versus 98.0% at 10 years of event-free follow-up for patients with pT1aN0 disease, relative to baseline. Conversely, pT4N0/pTanyN1 conditional CSM-free survival estimates were 55.8% at 1 year versus 77.9% at 8 years of event-free follow-up. Attrition due to mortality was highest in patients with pT4N0/pTanyN1 disease. In multivariable Cox regression analyses, T stage, tumor grade, and histologic subtype represented independent predictors, but no interactions were identified. Conclusions: Tumor stage and its substages represent extremely important determinants of prognosis after lengthy event-free follow-up. The recorded observations have critical importance for physicians regarding patient follow-up and counseling.
