Objectives
Aims of this SR were to assess the association of Periodontitis (PD) with Chronic Kidney Disease (CKD) and with different CKD stages.
Materials and methods
MEDLINE, Cochrane Central ...Register of Trials and EMBASE, up to April 4, 2021 were searched. RCTs, prospective and retrospective cohort studies, case–control studies and cross‐sectional studies were considered. JBI’s Critical Appraisal Tool for risk of bias assessment was used. The risk of PD was calculated using the Mantel–Haenszel odds ratios (MH‐OR); weighted mean difference for clinical attachment level (CAL) and periodontal probing depth (PPD) were also evaluated.
Results
Out of 1949 titles screened, 142 full texts were evaluated and 17 studies were included. CKD was associated to higher risk of PD (MH‐OR = 2.36, 95% C.I. 1.25, 4.44; p = 0.008), higher mean CAL (WMD = 0.41 mm 95% C.I. 0.22, 0.60; p < 0.0001) and mean PPD (WMD = 0.25 mm 95% C.I. 0.03, 0.47; p = 0.02) compared to healthy individuals. Severe CKD (stages 4–5 vs 2–3) resulted at higher risk of PD (MH‐OR = 2.21, 95% C.I. 1.07, 4.54; p = 0.03). Heterogeneity and risk of bias were high.
Conclusions
An association between PD and CKD was found. It could be appropriate to consider PD a frequent CKD comorbidity.
Although cancer-associated fibroblasts (CAF) are key determinants in the malignant progression of cancer, their functional contribution to this process is still unclear. Analysis of the mutual ...interplay between prostate carcinoma cells and CAFs revealed a mandatory role of carcinoma-derived interleukin-6 in fibroblast activation. In turn, activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases. CAF-induced EMT leads prostate carcinoma cells to enhance expression of stem cell markers, as well as the ability to form prostaspheres and to self-renew. Hence, the paracrine interplay between CAFs and cancer cells leads to an EMT-driven gain of cancer stem cell properties associated with aggressiveness and metastatic spread.
Cancer-associated fibroblasts (CAF) engage in tumor progression by promoting the ability of cancer cells to undergo epithelial-mesenchymal transition (EMT), and also by enhancing stem cells traits ...and metastatic dissemination. Here we show that the reciprocal interplay between CAFs and prostate cancer cells goes beyond the engagement of EMT to include mutual metabolic reprogramming. Gene expression analysis of CAFs cultured ex vivo or human prostate fibroblasts obtained from benign prostate hyperplasia revealed that CAFs undergo Warburg metabolism and mitochondrial oxidative stress. This metabolic reprogramming toward a Warburg phenotype occurred as a result of contact with prostate cancer cells. Intercellular contact activated the stromal fibroblasts, triggering increased expression of glucose transporter GLUT1, lactate production, and extrusion of lactate by de novo expressed monocarboxylate transporter-4 (MCT4). Conversely, prostate cancer cells, upon contact with CAFs, were reprogrammed toward aerobic metabolism, with a decrease in GLUT1 expression and an increase in lactate upload via the lactate transporter MCT1. Metabolic reprogramming of both stromal and cancer cells was under strict control of the hypoxia-inducible factor 1 (HIF1), which drove redox- and SIRT3-dependent stabilization of HIF1 in normoxic conditions. Prostate cancer cells gradually became independent of glucose consumption, while developing a dependence on lactate upload to drive anabolic pathways and thereby cell growth. In agreement, pharmacologic inhibition of MCT1-mediated lactate upload dramatically affected prostate cancer cell survival and tumor outgrowth. Hence, cancer cells allocate Warburg metabolism to their corrupted CAFs, exploiting their byproducts to grow in a low glucose environment, symbiotically adapting with stromal cells to glucose availability.
Abstract Context The correlation among metabolic syndrome, lower urinary tract symptoms (LUTS), and cardiovascular disease (CVD) is well established. In particular, CVD has been proposed as a ...potential risk factor for both LUTS progression and severity. Objective To evaluate whether LUTS severity can be considered as a significant risk factor of major adverse cardiac events (MACE) in the male population. Evidence acquisition A systematic literature search was performed using PubMed, Google Scholar, and Scopus. The combination of the following keywords was adopted in a free-text strategy: benign prostatic hyperplasia (BPH) or lower urinary tract symptoms (LUTS) and cardiovascular, cardio, major adverse cardiac events, MACE, heart disease, heart, myocardial infarction, myocardial, infarction, stroke, ischemic events, ischemic, cardiac death, coronary syndrome . We included all cross-sectional and longitudinal trials enrolling men and comparing the prevalence or incidence of MACE in men with moderate to severe LUTS compared with those without LUTS or with mild LUTS. The studies in which only nocturia was evaluated were excluded from the analysis. Evidence synthesis Of 477 retrieved articles, 5 trials longitudinally reported the incidence of MACE in patients with moderate to severe LUTS in comparisons to those with mild or no LUTS and 10 studies reported the prevalence of history of MACE at enrollment. All were included in the present meta-analysis. Among cross-sectional studies, 38 218 patients and 2527 MACE were included in the meta-analysis. The mean age of enrolled patients was 62.2 ± 8.0 yr. Presence of moderate to severe LUTS significantly increased the risk of reported history of MACE ( p < 0.001). Metaregression analyses showed that the risk of MACE was lower in older patients and higher in those with diabetes. The association between LUTS-related MACE and diabetes was confirmed in a multivariate regression model after adjusting for age (adjusted r = 0.498; p < 0.0001). Longitudinal trials included 25 494 patients and 2291 MACE. The mean age of enrolled patients was 52.5 ± 5.5 yr, and mean follow-up was 86.8 ± 22.1 mo. Presence of moderate to severe LUTS was associated with an increased incidence of MACE compared with the rest of the sample (odds ratio: 1.68; 95% confidence interval, 1.13–2.50; p = 0.01). Conclusions Men with moderate to severe LUTS seem to have an increased risk of MACE. A holistic approach in considering the morbidities of aging men should be strongly encouraged and represents an important role for the practicing urologist. Patient summary We evaluated whether the severity of lower urinary tract symptoms could be considered as a significant risk factor for major adverse cardiac events (MACE) in the male population. We demonstrated that men with moderate to severe LUTS have an increased risk of MACE.
Objective To evaluate perioperative results of open (OPN), laparoscopic (LPN), and robot-assisted partial nephrectomies (RAPN) and to identify predictive factors of Trifecta achievement for clinical ...T1b renal tumors in a multicenter prospective dataset. Methods Data of 285 patients who had OPN (133), LPN (57), or RAPN (95) for cT1b renal tumors were extracted from the RECORd Project. High-volume centers were defined as ≥50 overall cases of partial nephrectomy per year. Trifecta was defined as simultaneous absence of perioperative complications, negative surgical margins, and ischemia time <25 minutes. Results The 3 groups had comparable body mass index, preoperative hemoglobin, creatinine and estimated glomerular filtration rate, tumor clinical diameter, and growth pattern. LPN and RAPN were more frequently exclusive of high-volume centers. RAPN showed significantly lower median estimated blood loss compared with OPN and LPN. Trifecta was achieved in 62.4%, 63.2%, and 69.5% of OPN, LPN, and RAPN ( P = NS) cases. Median warm ischemia time (WIT) was significantly shorter during OPN than during LPN and RAPN. RAPN had significantly shorter WIT compared with LPN. RAPN was significantly less morbid than OPN regarding intraoperative and postoperative complications. LPN (1.9%) and RAPN (2.5%) showed a lower rate of positive margins compared with OPN (6.8%) ( P = NS). At multivariable analysis, exophytic tumor growth pattern, estimated blood loss, and high-volume centers were significant predictive factors for Trifecta achievement. Conclusion Clinically, T1b renal tumors suitable for NSS can be safely treated by LPN or RAPN in high-volume centers. RAPN allows for significantly lower WIT and estimated blood loss with higher rate of Trifecta achievement compared with LPN.
Several drugs, currently used to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH), can be associated with bothersome sexual side effects, including ejaculatory ...dysfunction (EjD).
To provide a systematic review and meta‐analysis of the available randomized clinical trials (RCTs) reporting the impact of medical treatments for LUTS due to BPH on ejaculatory function.
EjD related to medical treatments for LUTS.
A systematic literature search was performed using PubMed, Scopus and Cochrane databases. EjD was identified using both free text (“ejaculat*,” “retrograde ejaculation,” “anejaculation,” “ejaculatory dysfunction”) and Mesh (“Ejaculation”) searches.
Of 101 retrieved articles, 23 were included in the present meta‐analysis. EjD was significantly more common with alpha‐blockers (ABs) than with placebo (OR:5.88; P < 0.0001), in particular, considering Tamsulosin (OR:8.58; P = 0.006) or Silodosin (OR:32.5; P < 0.0001), with Tamsulosin associated with significantly lower risk of EjD than Silodosin (OR:0.09; P < 0.00001). Conversely, Doxazosin and Terazosin were associated with a risk similar to placebo. Meta‐regression showed that EjD was associated with IPSS and with Qmax both before and after treatment with ABs, while multivariate analysis demonstrated that EjD was independently associated with the improvement of IPSS (adj.r:0.2012; P < 0.0001) and Qmax (adj.r:0.522; P < 0.0001).
EjD was significantly more common with 5ARIs as compared with placebo (OR:2.73; P < 0.0001). Both Finasteride (OR 2.70; P < 0.0001) and Dutasteride (OR 2.81; P = 0.0002) were associated with significantly higher risk of EjD than placebo. EjD was significantly more common with combination therapy as compared with ABs alone (OR:3.75; P < 0.0001),or with 5ARIs alone (OR:2.76; P = 0.02).
ABs and 5ARI were both associated with significantly higher risk of EjD than placebo. More the AB is effective over time, greater is the incidence of EjD. Finasteride has the same risk of Dutasteride to cause EjD. Combination therapy with ABs and 5ARIs resulted in a 3‐fold increased risk of EjD as compared with ABs or 5ARIs alone. These data can be relevant both for drug selection and patients counseling. Gacci M, Ficarra V, Sebastianelli A, Corona G, Serni S, Shariat SF, Maggi M, Zattoni F, Carini M, and Novara G. Impact of medical treatments for male lower urinary tract symptoms due to benign prostatic hyperplasia on ejaculatory function: A systematic review and meta‐analysis. J Sex Med 2014;11:1554–1566.
Zoledronic acid (ZA) is a biphosphonate used for osteoporosis treatment and also proved to be effective to reduce the pain induced by bone metastases when used as adjuvant therapy in solid cancers. ...However, it has been recently proposed that ZA could have direct anti-tumour effects, although the molecular mechanism is unknown. We herein unravel a novel anti-tumour activity of ZA in prostate cancer (PCa), by targeting the pro-tumorigenic properties of both stromal and immune cells. Particularly, we demonstrate that ZA impairs PCa-induced M2-macrophages polarization, reducing their pro-invasive effect on tumour cells and their pro-angiogenic features. Crucially, ZA administration reverts cancer associated fibroblasts (CAFs) activation by targeting the mevalonate pathway and RhoA geranyl-geranylation, thereby impairing smooth muscle actin-α fibers organization, a prerequisite of fibroblast activation. Moreover, ZA prevents the M2 macrophages-mediated activation of normal fibroblast, highlighting the broad efficacy of this drug on tumour microenvironment. These results are confirmed in a metastatic xenograft PCa mouse model in which ZA-induced stromal normalization impairs cancer-stromal cells crosstalk, resulting in a significant reduction of primary tumour growth and metastases. Overall these findings reinforce the efficacy of ZA as a potential therapeutic approach to reduce cancer aggressiveness, by abrogating the supportive role of tumour microenvironment.
Sex and gender disparities have been reported for different types of non-reproductive cancers. Males are two times more likely to develop kidney cancer than females and have a higher death rate. ...These differences can be explained by looking at genetics and genomics, as well as other risk factors such as hypertension and obesity, lifestyle, and female sex hormones. Examination of the hormonal signaling pathways bring further insights into sex-related differences. Sex and gender-based disparities can be observed at the diagnostic, histological and treatment levels, leading to significant outcome difference. This review summarizes the current knowledge about sex and gender-related differences in the clinical presentation of patients with kidney cancer and the possible biological mechanisms that could explain these observations. Underlying sex-based differences may contribute to the development of sex-specific prognostic and diagnostic tools and the improvement of personalized therapies.
PDF
