Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy Among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-institutional Registry (REMARCC).

BACKGROUND: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved. OBJECTIVE: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN. DESIGN, SETTING, AND PARTICIPANTS: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores. RESULTS AND LIMITATIONS: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score. CONCLUSIONS: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein. PATIENT SUMMARY: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests.

A review of outcomes of an intracavernosal injection therapy programme.

UNLABELLED: Study Type--Therapy (outcomes research) Level of Evidence 2b. What's known on the subject? and What does the study add? Intracavernosal injection (ICI) therapy is an important treatment option for erectile dysfunction. However, high discontinuation rates have been reported for ICI therapy, and a risk of priapism has long been a concern. There has never been a large sample study performed with multivariate analysis to characterise outcomes of ICI therapy. The present paper reviews ICI therapy outcomes in a very large population of men at a tertiary care Sexual Medicine Clinic over 5 years. Multivariate analysis was used to further characterise these outcomes. The present study shows that for a large percentage of our sample of patients, ICI therapy is a successful treatment strategy. And, while discontinuation rates are still high, many of those not continuing ICI therapy achieved success with phosphodiesterase inhibitors. Also, the incidence of priapism was less in the present study than previously reported. OBJECTIVES: • To review the outcomes, adverse events and discontinuation rates of intracavernosal injection (ICI) therapy in men with erectile dysfunction (ED) in a sexual medicine practice over a 5-year period at a tertiary referral centre. • Since 1983, ICI has become a staple therapeutic option and high success rates have been reported. However, priapism is a significant concern and discontinuation rates are estimated to be >50%. PATIENTS AND METHODS: • Men presenting with ED who were enrolled in our ICI programme between September 2002 and August 2006 were followed at least annually. • Patient demographic information, agents used, erectile function outcomes and adverse events were recorded. • Failure was defined as the inability to have penetrative sex. Discontinuation was defined as patient declaration of such, failure to attend an annual follow-up visit or failure to call for a repeat prescription. • Multivariable analysis was used to define predictors of failure to respond to ICI therapy, as well as predictors of discontinuation within 36 months of starting ICI in those patients responding. RESULTS: • In all, 1412 patients had complete data and constituted the study population. Most patients were using Trimix and 89% of Trimix users were capable of having sexual intercourse. • Response rates were lower in pelvic radiation and diabetic patients. • However, the discontinuation rate was significant; it was lower in men who had not undergone radical prostatectomy (RP). Of note, many RP patients discontinued ICI because of recovery of natural or phosphodiesterase type 5 inhibitor-assisted erections. CONCLUSIONS: • ICI therapy is associated with very high success rates even in men with high comorbidity profiles; however, the discontinuation rates, even in men who had not undergone RP, by the end of the third year are significant. • Of note, the recorded priapism rate was extremely low (0.5%).

Construction of a microstructured collagen membrane mimicking the papillary dermis architecture and guiding keratinocyte morphology and gene expression.

A papillary-structured collagen fibril membrane is created, mimicking the 3D-architecture of the human papillary dermis. Primary human keratinocytes cultured to confluency on papillar-structured films are compared to keratinocytes cultured on flat membranes. Microscopical evaluation reveals the presence of morphologically distinct cells at the base of the papillar structures that are not observed on flat membranes. Gene expression microarrays and RT-qPCR indicate that these cells are in a more proliferative/migrational state, whereas cells on flat membranes have a more differentiated expression profile. Immunohistochemical stainings confirm these results. In conclusion, specific collagen architecture can direct keratinocyte behavior, and this may be used to further improve skin regeneration.