PADRES: a phase 2 clinical trial of neoadjuvant axitinib for complex partial nephrectomy.

OBJECTIVE: To report the results of PADRES (Prior Axitinib as a Determinant of Outcome of Renal Surgery, NCT03438708), a study investigating neoadjuvant axitinib for tumours of high complexity with imperative indication for partial nephrectomy (PN). METHODS: We conducted a single-arm phase II clinical trial of localized (cT1b-cT3M0) clear-cell renal cell carcinoma (RCC) patients with imperative indications for nephron preservation, where PN is a high-risk procedure due to complexity (RENAL score 10-12). Axitinib 5 mg was administered twice daily for 8 weeks with repeat imaging at completion, followed by surgery. The primary outcome was successful completion of planned PN following axitinib treatment. Secondary objectives included changes in tumour diameter, RENAL nephrometry score, renal function and Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, and surgical complications. RESULTS: Twenty-seven patients were enrolled (median age 69 years). Prior to therapy, twenty patients (74.0%) had ≥ clinical T3a staged tumours. Axitinib resulted in reductions in tumour diameter (7.5 vs 6.2 cm; P < 0.001) and RENAL score (11 vs 10; P < 0.001). Nine patients (33.3%) had partial response based on RECIST and nine (33.3%) were clinically downstaged. PN was performed in twenty patients (74.0%); twenty-five patients (96.2%) had negative margins. Six patients (22.2%) had Clavien III-IV complications. The median change in estimated glomerular filtration rate (preoperative to last follow-up) was 8.5 mL/min/1.73 m2 . CONCLUSION: Neoadjuvant axitnib resulted in reductions in tumour size and complexity, enabling safe and feasible PN and functional preservation in patients with complex renal masses and imperative indication.

The hospital frailty risk score as a predictor of readmission after ERCP.

BACKGROUND AND AIMS: The 30-day readmission rate is a nationally recognized quality measure with nearly one-fifth of patients being readmitted. This study aims to evaluate frailty, as measured by the hospital frailty risk score (HFRS), as a prognostic indicator for 30-day readmission after inpatient ERCP. METHODS: We analyzed weighted discharge records from the 2017 Nationwide Readmissions Database (NRD) to identify patients undergoing ERCP between 01/01/2017 and 11/30/2017. Our primary outcome was the 30-day unplanned readmission rate in frail (defined as HFRS > 5) against non-frail (HFRS < 5) patients. A mixed effects multivariable logistic regression method was employed. RESULTS: Among 68,206 weighted hospitalized patients undergoing ERCP, 31.3% were frail. Frailty was associated with higher 30-day readmission (OR 1.23, 95% CI [1.16-1.30]). Multivariable analysis showed a greater risk of readmission with cirrhosis (OR 1.26, 95% CI [1.10-1.45]), liver transplantation (OR 1.36, 95% CI [1.08-1.71]), cancer (OR 1.58, 95% CI [1.48-1.69]), and male gender (OR 1.24, 95% CI [1.18-1.31]). Frail patients also had higher mortality rate (1.8% vs 0.6%, p < 0.01)], longer LOS during readmission (6.7 vs 5.6 days, p < 0.01), and incurred more charges from both hospitalizations ($175,620 vs $132,519, p < 0.01). Sepsis was the most common primary indication for both frail and non-frail readmissions but accounted for a greater percentage of frail readmissions (17.9% vs 12.4%, p < 0.01). CONCLUSIONS: Frailty is associated with higher readmission rates, mortality, LOS, and hospital charges for admitted patients undergoing ERCP. Sepsis is the leading cause for readmission. Independent risk factors for readmission include liver transplantation, cancer, cirrhosis, and male gender.

Impact of worsening surgically induced chronic kidney disease (CKD-S) in preoperative CKD-naïve patients on survival in renal cell carcinoma.

OBJECTIVES: To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC). PATIENTS AND METHODS: We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 ). Patients were stratified by CKD stage at last follow-up: no CKD-S (eGFR ≥60 mL/min/1.73 m2 ), de novo CKD-S 3a (eGFR 45-59 mL/min/1.73 m2 ), CKD-S 3b (eGFR <45 and ≥30 mL/min/1.73 m2 ) and CKD-S 4 (eGFR <30 and ≥15 mL/min/1.73 m2 ). The primary outcome was all-cause mortality (ACM). Secondary outcomes included non-cancer mortality (NCM), cancer-specific mortality (CSM) and de novo CKD-S Stage 3/4. Multivariable analysis (MVA) was utilised to identify risk factors for outcomes. Kaplan-Meier analysis (KMA) was utilised to evaluate overall (OS), non-cancer (NCS), and cancer-specific survival with respect to CKD-S categories. RESULTS: We analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 m2 , respectively. On last follow-up, 57.9% (n = 1876) had no CKD-S, 18.7% (n = 606) had CKD-S 3a, 15.1% (n = 489) had CKD-S 3b and 8.3% (n = 268) had CKD-S 4. On MVA, de novo CKD-S 3b and 4 were independently associated with ACM (hazard ratios [HRs] 1.3-2.1, P = 0.003-0.001) and NCM (HRs 1.5-2.8, P = 0.021-0.001), but not CSM (P = 0.219-0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (P = 0.102-0.81). RN was independently associated with CKD-S 3-4 (HRs 1.78-1.99, P < 0.001-0.035). Comparing no CKD-S, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5-year OS 84% vs 78% vs 71% vs 60% (P < 0.001) and 5-year NCS 93% vs 87% vs 83% vs 72% (P < 0.001). CONCLUSION: Development of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

Partial or radical nephrectomy for complex renal mass: a comparative analysis of oncological outcomes and complications from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

PURPOSE: To compare outcomes of robotic-assisted partial nephrectomy (RAPN) and minimally invasive radical nephrectomy (MIS-RN) for complex renal masses (CRM). METHODS: We conducted a retrospective multicenter analysis of CRM patients who underwent MIS-RN and RAPN. CRM was defined as RENAL score 10-12. Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), recurrence, and complications. Multivariable analysis (MVA) and Kaplan-Meier Analysis (KMA) were used to analyze functional and survival outcomes for RN vs. PN by pathological stage. RESULTS: 926 patients were analyzed (MIS-RN = 437/RAPN = 489; median follow-up 24.0 months). MVA demonstrated lack of transfusion (HR = 1.63, p = 0.005), low-grade (HR = 1.18, p = 0.018) and smaller tumor size (HR = 1.05, p < 0.001) were associated with OS. Younger age (HR = 1.01, p = 0.017), high-grade (HR = 1.18, p = 0.017), smaller tumor size (HR = 1.05, p < 0.001), and lack of transfusion (HR = 1.39, p = 0.038) were associated with CSS. Increasing tumor size (HR = 1.18, p < 0.001), high-grade (HR = 3.21, p < 0.001), and increasing age (HR = 1.02, p = 0.009) were independent risk factors for recurrence. Type of surgery was not associated with major complications (p = 0.094). For KMA of MIS-RN vs. RAPN for pT1, pT2 and pT3, 5-year OS was 85% vs. 88% (p = 0.078); 82% vs. 80% (p = 0.442) and 84% vs. 83% (p = 0.863), respectively. 5-year CSS was 98% for both procedures (p = 0.473); 94% vs. 92% (p = 0.735) and 91% vs. 90% (p = 0.581). 5-year non-CSS was 87% vs. 93% (p = 0.107); 87% for pT2 (p = 0.485) and 92% for pT3 for both procedures (p = 0.403). CONCLUSION: RAPN in CRM is not associated with increased risk of complications or worsened oncological outcomes when compared to MIS-RN and may be preferred when clinically indicated.

Health insurance relationship to sun protection practices and beliefs.

PURPOSE: Lower socioeconomic status is associated with decreased sun protection practices. This survey study investigated practices and beliefs surrounding sun protection based on health insurance. METHODS: 401 surveys were administered May to June 2019 at two dermatology clinics in Sacramento, California. 384 surveys by private insurance, Medi-Cal (California's Medicaid), and Medicare coverage were analyzed. RESULTS: Patients with Medi-Cal are twice as likely to rarely or never use sunscreen (OR=2.37; 95% CI 1.45-3.87; P<0.001) compared to those with private insurance. Patients with Medi-Cal or Medicare are less likely to use sunscreen (P<0.001), protective clothing (P=0.025), and sun avoidance (P=0.028). Medi-Cal patients more often used tanning beds (OR=4.90; 95% CI 1.30-18.50; P=0.019). Over half of patients with Medi-Cal agreed it is worth getting burned for a tan (54.6%, OR=2.54; 95% CI 1.41-4.62; P=0.0021). There were no significant differences in opinion that sunscreen is a hassle to apply or expensive. Groups did not differ significantly in ethnicities or skin type. CONCLUSION: Those with Medi-Cal are less likely to use all forms of sun protection and more likely to value tanning. Negative opinions of sunscreen and perceived knowledge and concern for skin cancer were similar, pointing to additional factors influencing these disparities.

A patient with anti-NXP2-positive dermatomyositis and syphilis.

Dermatomyositis is an auto-immune inflammatory myopathy that primarily affects the skin and muscle and can be triggered by exposure to various environmental factors. We present a patient with active syphilis infection who developed dermatomyositis and discuss the significance of anti-NXP2 autoantibody positivity.

Characteristics of patients hospitalized for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) at a Level 1 trauma center.

The purpose of this study is to further characterize the population that is hospitalized for a severe cutaneous drug reaction or that developed once during their hospitalization. We conducted a chart review of patients seen by a dermatologist at the University of California Davis Medical Center for the diagnosis of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Between January 2000 and July 2018, 25 cases of DRESS were diagnosed using RegiSCAR criteria. Twenty-two patients recovered, two were deceased, and one was transferred to another hospital. The most commonly implicated drugs in the development of DRESS were nafcillin (N=3) and carbamazepine (N=3). Of the 25 patients in our care, 88% developed eosinophilia, 50% developed renal involvement, and 44% had liver involvement. There was a positive correlation between age and creatine (P=0.01) and age and eosinophils (P=0.02). There was a negative correlation between age and liver enzyme abnormalities (AST P=0.01; ALT P=0.0003). Carbamazepine and nafcillin were commonly implicated drugs in DRESS. There was no significant difference between treatment group and patient outcome. Those who develop DRESS at an older age were more likely to have elevated creatinine and more profound eosinophilia, but were less likely to develop liver involvement.

Desmoplastic intradermal spitz nevi arising within red tattoo ink.

Tattoos present a diagnostic challenge for dermatologists. Various reactions to tattoo have been identified in the literature ranging from allergic, to infectious, to neoplastic. Of the neoplastic cases identified, it is unclear whether the tattoo ink was directly causative, or if the cases were merely coincidence, as the number of cutaneous malignancies has also been on the rise. We present a novel case of two desmoplastic intradermal Spitz nevi arising within red tattoo ink.

Retreatment for Lower Urinary Tract Symptoms After Water Vapor Thermal Therapy.

OBJECTIVE: To identify predictors of retreatment for symptomatic recurrence among men who undergo water vapor thermal therapy (WVTT; Rezum, Boston Scientific, Marlborough, MA), a minimally invasive surgical treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. METHODS: We retrospectively reviewed patients treated with WVTT at a single institution from August 2017 to February 2022. Patients who underwent a second benign prostatic hyperplasia procedure for persistent or recurrent lower urinary tract symptoms within 2years of original treatment were compared to the remaining cohort who did not undergo retreatment. Multivariate analysis was used to assess for predictors of retreatment. RESULTS: Data were obtained from 192 patients. 10 (5%) patients were retreated. The retreatment cohort had smaller prostate volumes (50.4±18.2 cc vs 48.5±35.7 cc; P = .003) and received a greater number of water vapor injections (4.4±1.8 vs 5.2±3.9; P < .001). At 6month follow-up, total International Prostate Symptom Score (IPSS; 10.13 ± 7.40 vs 18.5 ± 11.55, P = .044) and voiding subscores (4.59 ± 4.39 vs 9.5 ± 7.84, P = .006) were significantly worse in the retreatment group. On multivariate analysis, >1 treatment per lobe was independently associated with increased risk of retreatment (hazard ratio 8.509, 95% CI [1.109-65.293]; P = .039). CONCLUSION: WVTT has a low retreatment rate. Men who required retreatment received more injections and showed worsened voiding symptom scores 6months postoperatively. Decreasing the number of injections may help reduce treatment failure rates.

Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry.

BACKGROUND: To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). PATIENTS AND METHODS: We queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression were fitted to elucidate predictors of outcomes. RESULTS: Total 3902 patients (high CRP n = 1266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, P < .001), ccRCC (HR 2.69, P < .001), chRCC (HR 3.99, P < .001), pRCC (HR 1.76, P = .009) and vhRCC (HR 2.97, P =.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, P < .001), chRCC (HR 6.16, P = .003) and pRCC (HR 2.29, P = .011), while in vhRCC was not (P = .27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, P = .013), while in chRCC (P = .33), pRCC (P = .34) and vhRCC (P = .52) was not. On multivariable logistic regression CRP was a predictor of pRCC (OR 1.003, P = .002), while decreasing CRP was associated with benign tumors (OR 0.994, P = .048). CONCLUSION: Elevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non-vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.

Unraveling the BMI paradox in different renal cortical tumors: insights from the INMARC registry.

OBJECTIVE: To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). METHODS: We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. RESULTS: A total of 3,880 patients with a median follow-up of 31 (IQR 9-64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I-III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). CONCLUSION: Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes.

Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

OBJECTIVE: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC. METHODS: The INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups]. RESULTS: We analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (P = 0.026), male sex (P = 0.043), diabetes (P = 0.007), high/unclassified grade (P < 0.001-0.007), and variant histology (P = 0.017) as independent risk factors for increased risk, while papillary (P = 0.016) and chromophobe (P = 0.049) were associated with decreased risk. MVA identified high/unclassified grade (P = 0.003-0.004) and pT3a upstaging (P = 0.043) as predictive factors for worsened risk of CSM while papillary (P = 0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (P = 0.022), variant histology (P = 0.049), recurrence (P = 0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (P = 0.018) and RFS (P < 0.001), but not OS (P = 0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001). CONCLUSION: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC.

Assessing the mental health, physical health, and well-being of doctor of pharmacy students.

INTRODUCTION: Student well-being is a growing area of interest, though existing literature assessing multiple areas of well-being is lacking. This study aimed to evaluate the well-being of pharmacy students corresponding to three well-being domains (physical health, mental health, personal well-being and burnout) and identify characteristics associated with these domains. METHODS: An online survey adapted from various instruments was disseminated to pharmacy students from 11 pharmacy programs. Survey responses were compared using basic descriptive statistics, and Pearson's chi-Square was used for association analyses. RESULTS: Eight hundred thirty-six students from responded to the survey (24.3% response rate). For physical health, 59.3% of students reported sleeping <7  hours per night and 60.4% reported exercising 1 to 5  hours per week. For mental health, 24.8% of students screened positive for depression and 42% screened positive for anxiety. Lastly, 65.9% of students were at risk for decreased well-being and 63.7% for burnout. Based on association analyses, gender and pharmacy year were associated with screening positive for anxiety and burnout, gender was associated with decreased well-being, and relationship status was associated with screening positive for depression. CONCLUSIONS: This study revealed pharmacy students are at risk for lack of sleep and exercise, depression or anxiety, decreased well-being, and burnout. Also, several characteristics were found to be associated with these negative well-being outcomes. Although response rate and participant demographics could impact the generalizability of these findings, findings further increase awareness about student well-being and inform pharmacy programs supporting well-being by better understanding student risks.

Clinical Evaluation of Miniature Flexible Scope for Diagnosis of Ureteroscope Working Channel Defects.

Introduction: To evaluate flexible ureteroscope working channels with a 1.06 mm digital borescope (Clarus Medical, Minneapolis, MN) and identify factors contributing to ureteroscope damage over time. Materials and Methods: We performed a single institutional prospective study of patients undergoing stone surgery using a nondisposable flexible ureteroscope. A 1.06 mm borescope was used to evaluate ureteroscopes before and after surgery. Borescope videos were reviewed by two independent researchers to quantify average pre- and postprocedural damage. Results: Twenty-five procedures were performed with pre- and postprocedural borescope assessment between August 2021 and February 2022. All patients received preoperative CT imaging depicting a mean axial stone size of 14.1 ± 8.4 mm and density of 923.4 ± 458.1 HU. Mean operative time was 63.8 ± 34.0 minutes. The average number an instrument passes through the working channel was 2.1 ± 1.6. Laser was used in 11 cases with mean laser time of 18.8 ± 19.7 minutes and mean total energy of 5.8 ± 4.2 KJ. On preoperative assessment, all ureteroscopes had some form of defect (24% shave, 32% pinhole, 96% dents and scratches, and 28% discolorations). During postoperative assessment, 23/25 (92%) ureteroscopes showed additional damage with an average of 3.7 ± 2.8 imperfections acquired after one use. Significant differences were seen in acquired shavings (p = 0.028) and scratches or dents (p = 0.018). Of the 355 imperfections seen on postoperative evaluation, 0.4% were shave, 3% were pinhole, 85.8% were dents and scratches, and 10.8% were discolorations. Conclusion: The Clarus borescope observed defects after the majority of flexible ureteroscopy procedures for nephrolithiasis. Although such disruptions may not immediately render ureteroscopes nonfunctional, they are more common than previously described and could increase maintenance costs. Further studies are needed to investigate the burden of unit damage per procedure to raise operator awareness and reduce preventable ureteroscope imperfections.

Age-Related Differences in Oncological Outcomes in Renal Cell Carcinoma: Impact of Functional Conservation as Measured by Postoperative eGFR.

INTRODUCTION: We sought to determine whether loss of renal function increases risk of recurrence and metastases in renal cell carcinoma (RCC), and whether this impact was age-related. MATERIALS AND METHODS: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry. Patients were separated into younger (<65 years old) and elder (≥65 years old) age groups, and rates of de novo estimated glomerular filtration rate (eGFR<45 mL/min/1.73m2 [eGFR<45]) were calculated. Multivariable analysis (MVA) was conducted for predictors of progression-free survival (PFS) and all-cause mortality (ACM). Kaplan-Meier Analysis (KMA) was conducted for PFS and overall survival (OS) in younger and elder age groups stratified by functional status. RESULTS: We analyzed 1805 patients (1113 age<65, 692 age≥65). On MVA in patients <65, de novo eGFR<45 was independently associated with greater risk for worsened progression (HR=1.61, P=.038) and ACM (HR=1.82, P=.018). For patients ≥65, de novo eGFR<45 was not independently associated with progression (P=.736), or ACM (P=.286). Comparing patients with de novo eGFR<45 vs. eGFR ≥45, KMA demonstrated worsened 5-year PFS and OS in patients <65 (PFS: 68% vs. 86%, P<.001; OS: 73% vs. 90%, P<.001), while in patients ≥65, only 5-year OS was worsened (77% vs. 81%, P<.021). CONCLUSION: Development of de novo eGFR<45 was associated with more profound impact on patients <65 compared to patients ≥65, being an independent risk factor for PFS and ACM. The mechanisms of this phenomenon are unclear but underscore desirability for nephron preservation when safe and feasible in younger patients.

Partial versus radical nephrectomy for complex renal mass: multicenter comparative analysis of functional outcomes (Rosula collaborative group).

BACKGROUND: Utility of partial nephrectomy (PN) for complex renal mass (CRM) is controversial. We determined the impact of surgical modality on postoperative renal functional outcomes for CRM. METHODS: We retrospectively analyzed a multicenter registry (ROSULA). CRM was defined as RENAL Score 10-12. The cohort was divided into PN and radical nephrectomy (RN) for analyses. Primary outcome was development of de-novo estimated glomerular filtration rate (eGFR)<45 mL/min/1.73 m2. Secondary outcomes were de-novo eGFR<60 and ΔeGFR between diagnosis and last follow-up. Cox proportional hazards was used to elucidate predictors for de-novo eGFR<60 and <45. Linear regression was utilized to analyze ΔeGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year freedom from de-novo eGFR<60 and <45. RESULTS: We analyzed 969 patients (RN=429/PN=540; median follow-up 24.0 months). RN patients had lower BMI (P<0.001) and larger tumor size (P<0.001). Overall postoperative complication rate was higher for PN (P<0.001), but there was no difference in major complications (Clavien III-IV; P=0.702). MVA demonstrated age (HR=1.05, P<0.001), tumor-size (HR=1.05, P=0.046), RN (HR=2.57, P<0.001), and BMI (HR=1.04, P=0.001) to be associated with risk for de-novo eGFR<60 mL/min/1.73 m2. Age (HR=1.03, P<0.001), BMI (HR=1.06, P<0.001), baseline eGFR (HR=0.99, P=0.002), tumor size (HR=1.07, P=0.007) and RN (HR=2.39, P<0.001) were risk factors for de-novo eGFR<45 mL/min/1.73 m2. RN (B=-10.89, P<0.001) was associated with greater ΔeGFR. KMA revealed worse 5-year freedom from de-novo eGFR<60 (71% vs. 33%, P<0.001) and de-novo eGFR<45 (79% vs. 65%, P<0.001) for RN. CONCLUSIONS: PN provides functional benefit in selected patients with CRM without significant increase in major complications compared to RN, and should be considered when technically feasible.

Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.

BACKGROUND: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). METHODS: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. RESULTS: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). CONCLUSIONS: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.

Development of a novel score (RENSAFE) to determine probability of acute kidney injury and renal functional decline post surgery: A multicenter analysis.

OBJECTIVE: To create and validate 2 models called RENSAFE (RENalSAFEty) to predict postoperative acute kidney injury (AKI) and development of chronic kidney disease (CKD) stage 3b in patients undergoing partial (PN) or radical nephrectomy (RN) for kidney cancer. METHODS: Primary objective was to develop a predictive model for AKI (reduction >25% of preoperative eGFR) and de novo CKD≥3b (<45 ml/min/1.73m2), through stepwise logistic regression. Secondary outcomes include elucidation of the relationship between AKI and de novo CKD≥3a (<60 ml/min/1.73m2). Accuracy was tested with receiver operator characteristic area under the curve (AUC). RESULTS: AKI occurred in 452/1,517 patients (29.8%) and CKD≥3b in 116/903 patients (12.8%). Logistic regression demonstrated male sex (OR = 1.3, P = 0.02), ASA score (OR = 1.3, P < 0.01), hypertension (OR = 1.6, P < 0.001), R.E.N.A.L. score (OR = 1.2, P < 0.001), preoperative eGFR<60 (OR = 1.8, P = 0.009), and RN (OR = 10.4, P < 0.0001) as predictors for AKI. Age (OR 1.0, P < 0.001), diabetes mellitus (OR 2.5, P < 0.001), preoperative eGFR <60 (OR 3.6, P < 0.001) and RN (OR 2.2, P < 0.01) were predictors for CKD≥3b. AUC for RENSAFE AKI was 0.80 and 0.76 for CKD≥3b. AKI was predictive for CKD≥3a (OR = 2.2, P < 0.001), but not CKD≥3b (P = 0.1). Using 21% threshold probability for AKI achieved sensitivity: 80.3%, specificity: 61.7% and negative predictive value (NPV): 88.1%. Using 8% cutoff for CKD≥3b achieved sensitivity: 75%, specificity: 65.7%, and NPV: 96%. CONCLUSION: RENSAFE models utilizing perioperative variables that can predict AKI and CKD may help guide shared decision making. Impact of postsurgical AKI was limited to less severe CKD (eGFR<60 ml/min 71.73m2). Confirmatory studies are requisite.

Effects of BPA, BPS, and BPF on Oxidative Stress and Antioxidant Enzyme Expression in Bovine Oocytes and Spermatozoa.

Bisphenol A (BPA) and its analogs, bisphenol S (BPS) and bisphenol F (BPF), might impact fertility by altering oxidative stress pathways. Here, we hypothesize that bisphenols-induced oxidative stress is responsible for decreased gamete quality. In both female (cumulus-oocyte-complexes-COCs) and male (spermatozoa), oxidative stress was measured by CM-H2DCFDA assay and key ROS scavengers (SOD1, SOD2, GPX1, GPX4, CAT) were quantified at the mRNA and protein levels using qPCR and Western blot (COCs)/immunofluorescence (sperm). Either gamete was treated in five groups: control, vehicle, and 0.05 mg/mL of BPA, BPS, or BPF. Our results show elevated ROS in BPA-treated COCs but decreased production in BPS- and BPF-treated spermatozoa. Additionally, both mRNA and protein expression of SOD2, GPX1, and GPX4 were decreased in BPA-treated COCs (p < 0.05). In sperm, motility (p < 0.03), but not morphology, was significantly altered by bisphenols. SOD1 mRNA expression was significantly increased, while GPX4 was significantly reduced. These results support BPA's ability to alter oxidative stress in oocytes and, to a lesser extent, in sperm. However, BPS and BPF likely act through different mechanisms.

The SHARE Study: Pilot Study of a Communication Intervention Designed to Elicit Advanced-Stage Cancer Patients' Preferences and Goals.

Background: Helping seriously ill cancer patients identify and communicate their care preferences improves outcomes. Objective: The aim of this study was to pilot test the feasibility and acceptability of an intervention designed to elicit patients' preferences and goals of care and share them with their oncology teams. Design: A single-arm pilot study of a 2.5-minute video, 3-page brief questionnaire, and a wallet card with question prompts was conducted. Primary outcomes were feasibility (≥60% approach-to-consent ratio, ≥60% participants rated the intervention positively) and acceptability (≥60% recommended the intervention). Secondary outcomes, measured pre- and post-intervention, included patient anxiety and distress, hope, quality of life, and therapeutic alliance. Setting/subjects: The study subjects were advanced-stage cancer patients and their clinicians at a U.S. academic and community oncology practice. Results: Among 59 potentially eligible patients, 53 agreed to participate (90% approach-to-consent ratio); 4 were nonevaluable due to death. Overall, 45 of 49 patients (92%) rated their experience as excellent, very good, or good. Participants (mean age = 63 years, range 40-86) agreed or strongly agreed that they would recommend the video (83%), brief questionnaire (88%), and wallet card (63%). However, only 34% of participants reported reviewing the questionnaire with their oncologist. There were no increases in patient anxiety or distress associated with the intervention or reductions in hope or therapeutic alliances with oncologists (all p > 0.05); quality of life was better post-intervention (p = 0.02). Conclusions: This communication intervention that combined a video, questionnaire, and wallet card was both feasible and acceptable for helping advanced cancer patients identify their care preferences and goals and should be tested in a future randomized clinical trial. Clinical Trial Registration: ClinicalTrials.gov NCT03392090.