Role of Serum High-Sensitivity C-Reactive Protein as a Predictor of Therapeutic Response to Tadalafil in Patients With Erectile Dysfunction: A Prospective Observational Study.

INTRODUCTION: High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is known to be elevated in patients with erectile dysfunction (ED). However, its role in predicting therapeutic response to phosphodiesterase-5 inhibitors is incompletely understood. AIM: The aim of this study was to understand the relationship among hs-CRP, mechanism of ED, and therapeutic response of ED to tadalafil, a phosphodiesterase-5 inhibitor. METHODS: A total of 282 men (mean age 36.6 ± 12.0 years) with ED were included. All subjects underwent detailed evaluation, including estimation of a 6-item abbreviated version of the International Index of Erectile Function (IIEF-6) score, penile Doppler studies, and measurement of hs-CRP. IIEF-6 scoring and hs-CRP measurement were repeated after 6 weeks of tadalafil therapy (10 mg/day). The patients were categorized into vasculogenic and nonvasculogenic ED groups based on penile Doppler findings. MAIN OUTCOME MEASURE: The main outcome measure was the therapeutic response to tadalafil, in relation to the mechanism of ED and hs-CRP levels. RESULTS: Vasculogenic ED was much less common (23.8% of the subjects) than non-vasculogenic ED. Subjects with vasculogenic ED were older, had higher prevalence of cardiovascular risk factors, had more severe (mean IIEF-6 score 9.2 ± 4.6 vs 14.8 ± 4.7; P < .001) and longer duration ED, and responded less favorably to therapy (response rate 10.4% vs 75.0%; P < .001). Those showing improvement with tadalafil had lower hs-CRP at baseline (median 1.5 mg/L [interquartile range 0.9-2.3] vs 2.0 mg/L [interquartile range 1.1-3.1; P = .034]) and had proportionately greater reduction in its level. However, on multivariate analysis, only shorter duration of ED (P = .008), non-vasculogenic origin (P = .025), and higher IIEF-6 score at baseline (P = .013) were independent predictors of response to treatment. CLINICAL IMPLICATIONS: Serum hs-CRP is elevated in patients who are less likely to respond to vasodilator therapy but does not have an independent predictive value for this purpose. STRENGTHS & LIMITATIONS: This is the largest study to evaluate the relationship among the mechanism of ED, serum hs-CRP level, and therapeutic response of ED to tadalafil. All patients underwent a penile Doppler study to characterize the type of ED. The limitations were nonrandomized nature of the study and nearly 22% dropout rate. CONCLUSION: Serum hs-CRP level is higher in vasculogenic ED compared with non-vasculogenic ED, and is associated with poorer response to tadalafil therapy. However, this association is not independent of underlying risk factors and mechanism of ED. Jamaluddin, Bansal M, Srivastava GK, et al. Role of Serum High-Sensitivity C-Reactive Protein as a Predictor of Therapeutic Response to Tadalafil in Patients With Erectile Dysfunction: A Prospective Observational Study. J Sex Med 2019;16:1912-1921.

PD-L1 expression and its clinicopathologic and genomic correlation in the non-small cell lung carcinoma patients: An Indian perspective.

BACKGROUND: Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients. MATERIALS AND METHODS: Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations. RESULTS: PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors. CONCLUSIONS: This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.

Renal cell carcinoma in ectopic pelvic kidney: A rare case report with relevant surgical anatomy.

Renal Ectopia is a rare developmental anomaly, leading to failure of mature kidney to reach its normal location within the renal fossa. Most ectopic kidneys are asymphtomatic and gets diagnosed as incidental finding on radiography or at surgery. The incidence of RCC in ectopic kidney are very uncommon, presenting with atypical symptoms causes a diagnostic as well as therapeutic dilemma in front of urologists. We present a case of 65 years old gentleman, having complaints of hematuria having heterogeneously enhancing SOL in left pelvic ectopic kidney.