Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

BACKGROUND: Existing data on the impact of Hispanic ethnicity on outcomes for patients with renal cell carcinoma (RCC) is mixed. The authors investigated outcomes of Hispanic and non-Hispanic White (NHW) patients with advanced RCC receiving systemic therapy at large academic cancer centers using the International Metastatic Renal Cell Carcinoma Database (IMDC). METHODS: Eligible patients included non-Black Hispanic and NHW patients with locally advanced or metastatic RCC initiating systemic therapy. Overall survival (OS) and time to first-line treatment failure (TTF) were calculated using the Kaplan-Meier method. The effect of ethnicity on OS and TTF were estimated by Cox regression hazard ratios (HRs). RESULTS: A total of 1563 patients (181 Hispanic and 1382 NHW) (mostly males [73.8%] with clear cell RCC [81.5%] treated with tyrosine kinase inhibitor [TKI] monotherapy [69.9%]) were included. IMDC risk groups were similar between groups. Hispanic patients were younger at initial diagnosis (median 57 vs. 59 years, p = .015) and less likely to have greater than one metastatic site (60.8% vs. 76.8%, p < .001) or bone metastases (23.8% vs. 33.4%, p = .009). Median OS and TTF was 38.0 months (95% confidence interval [CI], 28.1-59.2) versus 35.7 months (95% CI, 31.9-39.2) and 7.8 months (95% CI, 6.2-9.0) versus 7.5 months (95% CI, 6.9-8.1), respectively, in Hispanic versus NHW patients. In multivariable Cox regression analysis, no statistically significant differences were observed in OS (adjusted hazard ratio [HR], 1.07; 95% CI, 0.86-1.31, p = .56) or TTF (adjusted HR, 1.06; 95% CI, 0.89-1.26, p = .50). CONCLUSIONS: The authors did not observe statistically significant differences in OS or TTF between Hispanic and NHW patients with advanced RCC. Receiving treatment at tertiary cancer centers may mitigate observed disparities in cancer outcomes.

Practical Prediction of New Baseline Renal Function After Partial Nephrectomy.

BACKGROUND: Partial nephrectomy (PN) is generally preferred for localized renal masses due to strong functional outcomes. Accurate prediction of new baseline glomerular filtration rate (NBGFR) after PN may facilitate preoperative counseling because NBGFR may affect long-term survival, particularly for patients with preoperative chronic kidney disease. Methods for predicting parenchymal volume preservation, and by extension NBGFR, have been proposed, including those based on contact surface area (CSA) or direct measurement of tissue likely to be excised/devascularized during PN. We previously reported that presuming 89% of global GFR preservation (the median value saved from previous, independent analyses) is as accurate as the more subjective/labor-intensive CSA and direct measurement approaches. More recently, several promising complex/multivariable predictive algorithms have been published, which typically include tumor, patient, and surgical factors. In this study, we compare our conceptually simple approach (NBGFRPost-PN = 0.90 × GFRPre-PN) with these sophisticated algorithms, presuming that an even 90% of the global GFR is saved with each PN. PATIENTS AND METHODS: A total of 631 patients with bilateral kidneys who underwent PN at Cleveland Clinic (2012-2014) for localized renal masses with available preoperative/postoperative GFR were analyzed. NBGFR was defined as the final GFR 3-12 months post-PN. Predictive accuracies were assessed from correlation coefficients (r) and mean squared errors (MSE). RESULTS: Our conceptually simple approach based on uniform 90% functional preservation had equivalent r values when compared with complex, multivariable models, and had the lowest degree of error when predicting NBGFR post-PN. CONCLUSIONS: Our simple formula performs equally well as complex algorithms when predicting NBGFR after PN. Strong anchoring by preoperative GFR and minimal functional loss (≈ 10%) with the typical PN likely account for these observations. This formula is practical and can facilitate counseling about expected postoperative functional outcomes after PN.

Fully Automated Versions of Clinically Validated Nephrometry Scores Demonstrate Superior Predictive Utility versus Human Scores.

OBJECTIVE: To automate the generation of three validated nephrometry scoring systems on preoperative computerised tomography (CT) scans by developing artificial intelligence (AI)-based image processing methods. Subsequently, we aimed to evaluate the ability of these scores to predict meaningful pathological and perioperative outcomes. PATIENTS AND METHODS: A total of 300 patients with preoperative CT with early arterial contrast phase were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer. A deep neural network approach was used to automatically segment kidneys and tumours, and then geometric algorithms were used to measure the components of the concordance index (C-Index), Preoperative Aspects and Dimensions Used for an Anatomical classification of renal tumours (PADUA), and tumour contact surface area (CSA) nephrometry scores. Human scores were independently calculated by medical personnel blinded to the AI scores. AI and human score agreement was assessed using linear regression and predictive abilities for meaningful outcomes were assessed using logistic regression and receiver operating characteristic curve analyses. RESULTS: The median (interquartile range) age was 60 (51-68) years, and 40% were female. The median tumour size was 4.2 cm and 91.3% had malignant tumours. In all, 27% of the tumours were high stage, 37% high grade, and 63% of the patients underwent partial nephrectomy. There was significant agreement between human and AI scores on linear regression analyses (R ranged from 0.574 to 0.828, all P < 0.001). The AI-generated scores were equivalent or superior to human-generated scores for all examined outcomes including high-grade histology, high-stage tumour, indolent tumour, pathological tumour necrosis, and radical nephrectomy (vs partial nephrectomy) surgical approach. CONCLUSIONS: Fully automated AI-generated C-Index, PADUA, and tumour CSA nephrometry scores are similar to human-generated scores and predict a wide variety of meaningful outcomes. Once validated, our results suggest that AI-generated nephrometry scores could be delivered automatically from a preoperative CT scan to a clinician and patient at the point of care to aid in decision making.

New drug approvals in prostate cancer and their effect on the treatment landscape.

Prostate cancer is the most frequently diagnosed non-skin cancer and the second leading cause of cancer-related mortality in men in the United States. Over the past decade, the treatment landscape for advanced prostate cancer has rapidly shifted. For decades, androgen deprivation therapy has been the cornerstone of systemic treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, more recently, we have seen the emergence of doublet and triplet combinations in the mHSPC setting. At the same time, there is an expanding list of treatments for patients with metastatic castration-resistant prostate cancer (mCRPC), including hormonal treatments, chemotherapy, immunotherapy, bone-targeted agents, radioligand therapy, and targeted therapy. The shifting of the treatment landscape for advanced prostate cancer has raised many questions regarding patient selection, therapy choice, and sequencing of different approved agents, particularly in the mCRPC setting with the earlier use of chemotherapy and androgen receptor signaling inhibitors. Since then, multiple trials have been conducted to improve the management of mHSPC and delay its progression to mCRPC. This review article discusses various clinical trials that focus on novel therapeutic targets for prostate cancer and how the initiation of newer clinical trials has affected older therapies and trials.

Symbiotic maple saps minimize disruption of the mice intestinal microbiota after oral antibiotic administration.

This study was undertaken to evaluate the in vivo impact of new symbiotic products based on liquid maple sap or its concentrate. Sap and concentrate, with or without inulin (2%), were inoculated with Bifidobacterium lactis Bb12 and Lactobacillus rhamnosus GG valio at initial counts of 2-4 × 10(8) cfu mL(-1). The experiments started with intra-gastric administration of antibiotic (kanamycin 40 mg in 0.1 cc) (to induce microbiota disturbance and/or diarrhea) to 3-to-5-week-old C57BL/6 female mice followed by a combination of prebiotic and probiotics included in the maple sap or its concentrate for a week. The combination inulin and probiotics in maple sap and concentrate appeared to minimize the antibiotic-induced breakdown of mice microbiota with a marked effect on bifidobacterium and bacteroides levels, thus permitting a more rapid re-establishment of the baseline microbiota levels. Results suggest that maple sap and its concentrate represent good candidates for the production of non-dairy functional foods.

Dissecting the Significance of Acid Phosphatase 1 Gene Alterations in Prostate Cancer.

PURPOSE: The acid phosphatase 1 (ACP1) gene encodes low-molecular-weight protein tyrosine phosphatase, which is overexpressed in prostate cancer (PC) and a potential therapeutic target. We analyzed ACP1 expression in primary/metastatic PC and its association with molecular profiles and clinical outcomes. METHODS: NextGen sequencing of DNA (592-gene/whole-exome sequencing)/RNA(whole-transcriptome sequencing) was performed for 5,028 specimens. ACP1-High/ACP1-Low expression was defined as quartile (Q4/1) of RNA transcripts per million (TPM). DNA mutational profiles were analyzed for ACP1-quartile-stratified samples. Gene set enrichment analysis was used for Hallmark collection of pathways. PD-L1+(≥2+, ≥5%; SP142) was tested by immunohistochemistry. Tumor microenvironment's (TME) immune cell fractions were estimated by RNA deconvolution/quanTIseq. Overall survival (OS) was assessed from initial diagnosis/treatment initiation to death/last follow-up. RESULTS: We included 3,058 (60.8%) samples from the prostate, 634 (12.6%) from lymph node metastases (LNMs), and 1,307 (26.0%) from distant metastases (DMs). ACP1 expression was higher in LNM/DM than prostate (49.8/47.9 v 44.1 TPM; P < .0001). TP53 mutations were enriched in ACP1-Q4 (37.9%[Q4] v 27.0%[Q1]; P < .001) among prostate samples. Pathways associated with cell cycle regulation and oxidative phosphorylation were enriched in ACP1-Q4, whereas epithelial-mesenchymal transition and tumor necrosis factor-alpha signaling via nuclear factor kappa-light-chain-enhancer of activated B-cell pathways were enriched in ACP1-Q1. Neuroendocrine and androgen receptor signaling was increased in ACP1-Q4. M2 macrophages and natural killer cell fractions were increased, whereas T cells and M1 macrophages were decreased in ACP1-Q4. While OS differences between ACP1-Q1/Q4 were not statistically significant, there was a trend for worse OS among ACP1-Q4 prostate samples (Q4 v Q1: hazard ratio [HR], 1.19 [95% CI, 0.99 to 1.42]; P = .06) and DM (HR, 1.12 [95% CI, 0.93 to 1.36]; P = .22) but not LNM (HR, 0.98 [95% CI, 0.74 to 1.29]; P = .87). CONCLUSION: ACP1-High tumors exhibit a distinct molecular profile and cold TME, highlighting ACP1's potential role in PC pathogenesis and novel therapeutic targeting.

Trends in Lung Cancer Incidence and Mortality (1990-2019) in the United States: A Comprehensive Analysis of Gender and State-Level Disparities.

PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the United States. This study aims to analyze lung cancer incidence, mortality, and related statistics from 1990 to 2019, focusing on national- and state-level trends and exploring potential disparities between sexes. METHODS: The Global Burden of Disease database was used to extract tracheal, bronchus, and lung cancer mortality data from 1990 to 2019 for both males and females and across all states of the United States. Age-standardized incidence rates, age-standardized mortality rates, disability-adjusted life years (DALYs), and mortality-to-incidence indices (MIIs) were studied to assess for gender-based, geographic, and temporal disparities. Joinpoint regression analysis was performed to further evaluate trends. RESULTS: The incidence of these cancers in the United States decreased between 1990 and 2019 by 23.35%, with a more significant decline in males (37.73%) than females (1.41%). Similarly, for mortality, a decrease was observed for both sexes combined (26.83%), but much more significantly for males (40.23%) than females (6.01%). The MIIs decreased overall, but there were variations across states. DALYs decreased for both sexes combined, with males experiencing a larger reduction, but an increase was noted in some states for females. CONCLUSION: This analysis reveals diverse trends pertaining to the incidence, mortality, and disability burden associated with lung cancer by sex and states in the United States, emphasizing the need for targeted interventions to reduce disparities. These findings contribute to our understanding of the current landscape of lung cancer and can inform future strategies for prevention, early detection, and management.

Trends in prostate cancer mortality in the United States of America, by state and race, from 1999 to 2019: estimates from the centers for disease control WONDER database.

BACKGROUND: In the United States of America (USA), prostate cancer (PC) is the most common cancer in men and the second cause of cancer mortality. Black men (BM) have a higher incidence and worse mortality when compared to white men (WM). We compared trends in PC mortality in the USA by race and state from 1999 to 2019. METHODS: We extracted PC mortality data from the Centers for Disease Control (CDC) WONDER database using the International Classification of Diseases (ICD) 10 code C61. Age-Standardized Mortality Rates (ASMR) were divided into racial groups and reported by year and state. Due to the lack of available data in many states, analyses were conducted only for WM and BM using Joinpoint regression for trend comparisons. RESULTS: Between 1999-2019, ASMR decreased at the national level in Black (-44.6%), Asian (-44.8%), White (-31.8%), and American Indian or Alaskan native men (-19.0%). ASMR decreased in all states for both races. The greatest drop in ASMR was in Kentucky (-47.0%) for WM and Delaware (-57.8%) for BM. In 2019, ASMRs in BM (13.4/100 000) were significantly higher than WM (7.3/100 000), American Indian or Alaskan Native (3.2/100 000), and Asian men (3.2/100 000) (p < 0.001). The highest ASMRs were in Nebraska (33.5/100 000) for BM and Alaska (11/100 000) for WM. CONCLUSIONS: During the last 20 years, the PC mortality rate dropped in all states for all races, suggesting an advancement in management strategies. Although a higher decrease in ASMR was observed in BM, ASMR remain higher among BM. ASMRs were also found to be increasing in many states post USPSTF guideline change (2012), indicating a need for more education around optimized prostate cancer screening.

Point of care parenchymal volume analyses to estimate split renal function and predict functional outcomes after radical nephrectomy.

Accurate prediction of new baseline GFR (NBGFR) after radical nephrectomy (RN) can inform clinical management and patient counseling whenever RN is a strong consideration. Preoperative global GFR, split renal function (SRF), and renal functional compensation (RFC) are fundamentally important for the accurate prediction of NBGFR post-RN. While SRF has traditionally been obtained from nuclear renal scans (NRS), differential parenchymal volume analysis (PVA) via software analysis may be more accurate. A simplified approach to estimate parenchymal volumes and SRF based on length/width/height measurements (LWH) has also been proposed. We compare the accuracies of these three methods for determining SRF, and, by extension, predicting NBGFR after RN. All 235 renal cancer patients managed with RN (2006-2021) with available preoperative CT/MRI and NRS, and relevant functional data were analyzed. PVA was performed on CT/MRI using semi-automated software, and LWH measurements were obtained from CT/MRI images. RFC was presumed to be 25%, and thus: Predicted NBGFR = 1.25 × Global GFRPre-RN × SRFContralateral. Predictive accuracies were assessed by mean squared error (MSE) and correlation coefficients (r). The r values for the LWH/NRS/software-derived PVA approaches were 0.72/0.71/0.86, respectively (p < 0.05). The PVA-based approach also had the most favorable MSE, which were 120/126/65, respectively (p < 0.05). Our data show that software-derived PVA provides more accurate and precise SRF estimations and predictions of NBGFR post-RN than NRS/LWH methods. Furthermore, the LWH approach is equivalent to NRS, precluding the need for NRS in most patients.

Using IsoPSA With Prostate Imaging Reporting and Data System Score May Help Refine Biopsy Decision Making in Patients With Elevated PSA.

OBJECTIVE: To assess how IsoPSA, a structure-based serum assay which has been prospectively validated in detecting clinically significant prostate cancer (csPCa), can help the biopsy decision process when combined with the prostate imaging reporting and data systems (PI-RADS). MATERIALS AND METHODS: This was a single-center retrospective review of prospectively collected data on patients receiving IsoPSA testing for elevated PSA (>4.0ng/mL). Patients were included if they had received an IsoPSA test and prostate MRI within 1 year of IsoPSA testing, and subsequently underwent prostate biopsy. Multivariable logistic regression was used to identify predictors of (csPCa, ie, GG ≥ 2) on biopsy. Predictive probabilities for csPCa at biopsy were generated using IsoPSA and various PI-RADS scores. RESULTS: Two hundred and 7 patients were included. Twenty-two percent had csPCa. Elevated IsoPSA ratio (defined as ≥6.0) (OR: 5.06, P = .015) and a PI-RADS 4-5 (OR: 6.37, P <.001) were significant predictors of csPCa. The combination of elevated IsoPSA ratio and PI-RADS 4-5 lesion had the highest area under the curve (AUC) (AUC: 0.83, P <.001). The predicted probability of csPCa when a patient had a negative or equivocal MRI (PI-RADS 1-3) and a low IsoPSA ratio (≤6) was <5%. CONCLUSION: The combination of PI-RADS with IsoPSA ratios may help refine the biopsy decision-making process. In our cohort, a negative or equivocal MRI with a low IsoPSA may provide a low enough predicted probability to omit biopsy in such patients.

AI-generated R.E.N.A.L.+ Score Surpasses Human-generated Score in Predicting Renal Oncologic Outcomes.

OBJECTIVE: To determine whether we can surpass the traditional R.E.N.A.L. nephrometry score (H-score) prediction ability of pathologic outcomes by creating artificial intelligence (AI)-generated R.E.N.A.L.+ score (AI+ score) with continuous rather than ordinal components. We also assessed the AI+ score components' relative importance with respect to outcome odds. METHODS: This is a retrospective study of 300 consecutive patients with preoperative computed tomography scans showing suspected renal cancer at a single institution from 2010 to 2018. H-score was tabulated by three trained medical personnel. Deep neural network approach automatically generated kidney segmentation masks of parenchyma and tumor. Geometric algorithms were used to automatically estimate score components as ordinal and continuous variables. Multivariate logistic regression of continuous R.E.N.A.L. components was used to generate AI+ score. Predictive utility was compared between AI+, AI, and H-scores for variables of interest, and AI+ score components' relative importance was assessed. RESULTS: Median age was 60years (interquartile range 51-68), and 40% were female. Median tumor size was 4.2 cm (2.6-6.12), and 92% were malignant, including 27%, 37%, and 23% with high-stage, high-grade, and necrosis, respectively. AI+ score demonstrated superior predictive ability over AI and H-scores for predicting malignancy (area under the curve [AUC] 0.69 vs 0.67 vs 0.64, respectively), high stage (AUC 0.82 vs 0.65 vs 0.71, respectively), high grade (AUC 0.78 vs 0.65 vs 0.65, respectively), pathologic tumor necrosis (AUC 0.81 vs 0.72 vs 0.74, respectively), and partial nephrectomy approach (AUC 0.88 vs 0.74 vs 0.79, respectively). Of AI+ score components, the maximal tumor diameter ("R") was the most important outcomes predictor. CONCLUSION: AI+ score was superior to AI-score and H-score in predicting oncologic outcomes. Time-efficient AI+ score can be used at the point of care, surpassing validated clinical scoring systems.

West Nile virus: another emerging arboviral risk for travelers?

Purpose of Review: West Nile virus (WNV) is an arbovirus transmitted by mosquitos of the genus Culex. Manifestations of WNV infection range from asymptomatic to devastating neuroinvasive disease leading to flaccid paralysis and death. This review examines WNV epidemiology and ecology, with an emphasis on travel-associated infection. Recent Findings: WNV is widespread, including North America and Europe, where its range has expanded in the past decade. Rising temperatures in temperate regions are predicted to lead to an increased abundance of Culex mosquitoes and an increase in their ability to transmit WNV. Although the epidemiologic patterns of WNV appear variable, its geographic distribution most certainly will continue to increase. Travelers are at risk for WNV infection and its complications. Literature review identified 39 cases of documented travel-related WNV disease, the majority of which resulted in adverse outcomes, such as neuroinvasive disease, prolonged recovery period, or death. Summary: The prediction of WNV risk is challenging due to the complex interactions of vector, pathogen, host, and environment. Travelers planning to visit endemic areas should be advised regarding WNV risk and mosquito bite prevention. Evaluation of ill travelers with compatible symptoms should consider the diagnosis of WNV for those visiting in endemic areas as well as for those returning from destinations with known WNV circulation.

Trends of kidney cancer burden from 1990 to 2019 in European Union 15 + countries and World Health Organization regions.

In recent decades, variability in the incidence and mortality of kidney cancer (KC) has been reported. This study aimed to compare trends in incidence, mortality, and disability-adjusted life years (DALY) of KC between the European Union (EU) 15 + countries and 6 World Health Organization (WHO) regions. The data of KC Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and age-standardized DALYs were extracted from the Global Burden of Disease database. Joinpoint regression was employed to examine trends. From 1990 to 2019, the ASIR increased in most countries except for Luxembourg (males), the USA (females) and Austria and Sweden (both sexes). ASIR increased across all 6 WHO regions for both sexes except for females in Americas. The ASMR increased in 10/19 countries for males and 9/19 for females as well across most WHO regions. The mortality-to-incidence ratio (MIR) decreased in all countries and WHO regions. Trends in DALYs were variable across countries and WHO regions. While the incidence and mortality from KC rose in most EU15 + countries and WHO regions from 1990 to 2019, the universal drop in MIR suggests an overall improvement in KC outcomes. This is likely multifactorial, including earlier detection of KC and improved treatments.

Improving the safety of Staphylococcus aureus polyvalent phages by their production on a Staphylococcus xylosus strain.

Team1 (vB_SauM_Team1) is a polyvalent staphylococcal phage belonging to the Myoviridae family. Phage Team1 was propagated on a Staphylococcus aureus strain and a non-pathogenic Staphylococcus xylosus strain used in industrial meat fermentation. The two Team1 preparations were compared with respect to their microbiological and genomic properties. The burst sizes, latent periods, and host ranges of the two derivatives were identical as were their genome sequences. Phage Team1 has 140,903 bp of double stranded DNA encoding for 217 open reading frames and 4 tRNAs. Comparative genomic analysis revealed similarities to staphylococcal phages ISP (97%) and G1 (97%). The host range of Team1 was compared to the well-known polyvalent staphylococcal phages phi812 and K using a panel of 57 S. aureus strains collected from various sources. These bacterial strains were found to represent 18 sequence types (MLST) and 14 clonal complexes (eBURST). Altogether, the three phages propagated on S. xylosus lysed 52 out of 57 distinct strains of S. aureus. The identification of phage-insensitive strains underlines the importance of designing phage cocktails with broadly varying and overlapping host ranges. Taken altogether, our study suggests that some staphylococcal phages can be propagated on food-grade bacteria for biocontrol and safety purposes.