Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets.

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.

The Severity of Pain in Prostate Biopsy Depends on the Biopsy Sector.

BACKGROUND: The pain experienced by a patient during a prostate fusion biopsy is cumulative and can also be modulated by many factors. The aim of the study was to assess the association between the degree of pain intensity during prostate biopsy and the region of the biopted organ. MATERIALS AND METHODS: The study included a group of 143 patients who underwent prostate fusion biopsy under local analgesia followed by blockage of the periprostatic nerve. After a biopsy, the patients completed the original questionnaire about the pain experienced during the procedure. RESULTS: There was a statistically significant difference in pain score between cores taken in the apex (median 5 (IQR 2-5)), medium level (median 1 (IQR 1-2)), and prostate base (median 1 (IQR 1-3)) (p < 0.001). The malignancy scale ISUP ≥ 2 (p = 0.038) and lower PSA value (r = -0.17; p = 0.046) are associated with higher pain during procedure. Biopsy time was correlated with discomfort (r = 0.19; p = 0.04). Age (p = 0.65), lesion size (p = 0.29), PI-RADS score (p = 0.86), prostate volume (p = 0.22), and the number of cores (p = 0.56) did not correspond to the pain scale. CONCLUSIONS: The apex is the most sensitive sector of the prostate. ISUP ≥ 2 and patients with low PSA levels more often indicated higher values on the pain rating scale.

The influence of the operator's experience on the outcomes of fusion prostate biopsy.

Introduction: Magnetic resonance imgaing (MRI) targeted biopsy is the gold standard for prostate cancer (PCa) diagnosis. In this study, we examined the association between the operator's experience and the improvement in the precision of the MRI prostate biopsy procedure and the detection of PCa. Material and methods: We included consecutive patients who underwent prostate fusion biopsy. Data on biopsy duration, prostate-specific antigen (PSA) value, lesion size, number of samples taken, number of cores involved, and International Society of Urological Pathology (ISUP) grade were subjected to statistical analysis, with the study group divided into three consecutive time periods (tertiles). Results: There were statistically significant differences in biopsy duration between tertiles (p <0.001). The greatest difference in the involved/taken cores ratio occurred between the first and third tertile (p = 0.002). The difference between the first and second tertile was insignificant (p = 0.4), while the difference between the second and third tertile was statistically significant (p = 0.004). The differences between tertiles in Prostate Imaging and Reporting Data System v2.1 were also significant (p = 0.003). The PSA value (p = 0.036) was statistically significant, unlike prostate volume (p = 0.16), digital rectal examination (DRE) (p = 0.7), and ISUP grade (p = 0.7). There was no statistical difference between tested tertiles in the number of detected PCa ISUP ≥2 (Z = 0.191; p = 0.8). Conclusions: The abilities and precision of the operator increase with the increase in the number of procedures performed. The biopsy duration is shortened, and the detection of PCa during the procedure seems to improve with the operator's experience.

Awareness of testicular cancer among adult Polish men and their tendency for prophylactic self-examination: conclusions from Movember 2020 event.

BACKGROUND: Testicular cancer (TC), due to its non-specific symptoms and occurrence in young men, is particularly dangerous. A critical point for early diagnosis is awareness of the disease and the willingness to perform a testicular self-examination (TSE). The main aim of the study was to assess the knowledge of 771 adult men about testicular cancer. Additionally, the sources of information on TC and TSE were analyzed and the influence of demographic factors on the willingness to join preventative programs was examined. MATERIALS AND METHODS: The study was carried out during the Movember2020 campaign, where a testicular ultrasound was performed on participants. They were asked to complete a questionnaire with 26 questions to assess their knowledge. RESULTS: The results obtained in the study indicate a low level of knowledge (average 3.5 points out of 18) about TC. Living in a large city (OR = 1.467; p = 0.03), as well as an earlier conversation about TC (OR = 1.639; p = 0.002), increased the awareness about the disease. Additionally it showed that many participants do not perform TSE at all (52.4%) and that only few perform TSE frequently (18.4%). Relationship status (OR = 2.832; p < 0.001) and previous conversations about TC (OR = 1.546; p = 0.02) was reported to be the main contributing factors in males deciding to have TSE. CONCLUSIONS: Our research indicates large educational neglect in terms of knowledge about TC and reluctance in performing TSE. It is worth carrying out preventative actions periodically on an increasing scale, not only for the screening of testicular cancer, but also to expand knowledge on this subject.

Mean platelet volume-to-lymphocyte ratio: a novel biomarker associated with overall survival in patients with nonmetastatic clear cell renal cell carcinoma treated with nephrectomy.

INTRODUCTION: Renal cell carcinoma is a highly aggressive malignancy that causes significant morbidity and mortality. The rising number of newly diagnosed renal tumors results in a great need to search for new preoperative markers to evaluate the course of the disease and to help select patients who would benefit the most from additional postoperative care. The aim of our study was to evaluate the prognostic value of mean platelet volume-to-lymphocyte ratio (MPVLR) in patients undergoing nephrectomy for nonmetastatic clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A total number of 344 patients with proven nonmetastatic ccRCC treated with radical or partial nephrectomy at our institution between January 2003 and December 2012 were included in our analysis. Based on the optimal cut-off value of MPVLR, which was determined by the receiver operating characteristic curve, our study population was divided into two groups, with low and high MPVLR. Differences in overall survival between groups were compared using the Kaplan-Meier method with log-rank testing. The Cox proportional hazards regression model was applied to perform univariate and multivariate analysis. RESULTS: Study subjects with high MPVLR were older and had more advanced tumors. Tumor necrosis and higher TNM stages were also more prevalent in this group of patients. Mortality in patients with high MPVLR was significantly higher than in patients with low MPVLR. In the multivariate analysis, after adjustment for pathological and clinical covariates, high MPVLR (≥ 3.61) was independently associated with higher long-term overall mortality in nonmetastatic ccRCC patients. CONCLUSION: MPVLR is an easily obtainable prognostic marker for overall survival in nonmetastatic ccRCC patients treated with nephrectomy.

Mechanical circulatory support in heart failure.

The increasing number of end-stage heart failure patients eligible for heart transplant and the disproportionately low number of donor hearts have led to increased interest in ventricular assist devices (VAD). These devices can be used as a bridge to decision, bridge to recovery, or bridge to candidacy. The main advantage of mechanical circulatory support (MCS) is the improvement of organ perfusion and function, which leads to better quality of life and survival. The MCS can also be used as a destination therapy in end-stage heart failure patients who are not eligible for heart transplant. It should be remembered that, despite the tangible benefits, VAD implantation may also be associated with the risk of serious complications, such as bleeding, infection, arrhythmias, blood clots, right ventricular failure, and cardiovascular events. This study presents an up-to-date overview of the current knowledge on the role of MCS in modern medicine.