Shorter Ureters Lead to Fewer Strictures Following Cystectomy and Urinary Diversion.

OBJECTIVE: To identify the impact of length of distal ureteral resection on the risk of benign uretero-enteric anastomotic stricture (UEAS) formation following cystectomy and urinary diversion. METHODS: A database of patients who underwent cystectomy and urinary diversion from 2015 to 2022 was analyzed. Distal ureteral resections were sent for final pathology. The length of resected ureter was collected from pathology reports. Benign UEAS were confirmed with renal scintigraphy, antegrade nephrostogram, or endoscopic evaluation. The relationship between stricture formation and clinical parameters were assessed using T-tests, chi-square tests, and multivariable analysis. RESULTS: A total of 366 patients underwent cystectomy and urinary diversion. Of the cohort, 35 (9.5%) patients developed UEAS. Median time to stricture formation was 12.5months (IQR 4-30). Of the 711 uretero-enteric anastomoses, 40 (5.6%) ultimately formed a UEAS. Median distal ureteral resection was significantly longer among ureteral anastomoses which did not form a UEAS (2.3 cm vs 1.65 cm, P = .028). Multivariable logistic regression adjusting for surgical approach, prior radiation, ureteral side, and urinary diversion type demonstrated that longer distal ureteral resections were inversely associated with odds of UEAS formation (OR 0.73, 95% CI 0.58-0.92). Multivariable Cox regression analysis similarly showed that length of distal ureteral resection was inversely associated with time to stricture formation (HR 0.78, 95% CI 0.62-0.98). CONCLUSION: The etiology of benign UIA strictures is multifactorial. Vascular compromise is a critical hypothesis. We found that longer distal ureteral resections (and thus shorter ureters) were associated with a significantly lower risk of stricture formation in cystectomy patients.

Contemporary Patients Have Better Perioperative Outcomes Following Cytoreductive Nephrectomy: A Multi-institutional Analysis of 1272 Consecutive Patients.

OBJECTIVE: To evaluate factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with cytoreductive nephrectomy (CN). METHODS: Data were analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary academic centers from 2005 to 2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, 30-day readmission rate, and time to systemic therapy. Univariate and multivariable models evaluated associations between outcomes and prognostic variables including the year of surgery. RESULTS: A total of 1272 consecutive patients were treated with CN. Patients treated in 2015-2019 vs 2005-2009 had better performance status (P<.001), higher pathologic N stage (P = .04), more frequent lymph node dissections (P<.001), and less frequent presurgical therapy (P = .02). Patients treated in 2015-2019 vs 2005-2009 had lower overall and major complications from surgery, 22% vs 39%, P<.001% and 10% vs 16%, P = .03. Mortality at 90days was higher for patients treated 2005-2009 vs 2015-2019; 10% vs 5%, P = .02. After multivariable analysis, surgical time period was an independent predictor of major complications and 90-day mortality following cytoreductive surgery. CONCLUSION: Postoperative major complications and mortality rates following CN are significantly lower in patients treated within the most recent time period.

Understanding and integrating cytoreductive nephrectomy with immune checkpoint inhibitors in the management of metastatic RCC.

Cytoreductive nephrectomy became accepted as standard of care for selected patients with metastatic renal cell carcinoma (mRCC) because of improved survival observed in patients treated with cytoreductive nephrectomy in combination with interferon-α in two randomized clinical trials published in 2001. Over the past two decades, novel systemic therapies have shown higher treatment response rates and improved survival outcomes compared with interferon-α. During this rapid evolution of mRCC treatments, systemic therapies have been the primary focus of clinical trials. Results from multiple retrospective studies continue to suggest an overall survival benefit for selected patients treated with nephrectomy in combination with systemic mRCC treatments, with the notable exception of one debated clinical trial. The optimal timing for surgery is unknown, and proper patient selection remains crucial to improving surgical outcomes. As systemic therapies continue to evolve, clinicians have an increasing need to understand how to incorporate cytoreductive nephrectomy into the management of mRCC.

Biofeedback therapy for children: What is the maximum number of sessions we should offer?

BACKGROUND: Biofeedback therapy is an effective but resource intensive treatment for pediatric dysfunctional voiding. Based on our center's experience, we evaluated the rate of clinical improvement from biofeedback in order to identify the maximum number of sessions to offer patients. METHODS: We reviewed 490 pediatric patients who underwent at least 6 sessions of biofeedback from 2013 to 2021. At each session, patients and their parents documented their urinary symptoms (urgency, frequency, pain, and difficulties with stream), incontinence, medications, and stool pattern. This longitudinal data was abstracted, and the log odds of urinary symptoms or incontinence was modelled with number of sessions as a predictor using generalized estimating equations and robust standard errors in SAS v9.4. Gender and bowel dysfunction were included as interactions terms. A logistic regression using absence of urinary symptoms at last biofeedback session as a dependent variable was done to further explore differences between genders. RESULTS: Patients were predominantly female (324/490, 66%) with a mean age of 8.9 years (SD 3.3 years). Most common symptoms at presentation were urinary urgency (389/490, 79%) and urinary incontinence (413/490, 84%). Medication use was common at the time of the first session (191/490, 39%) with males more likely to be on alpha-blockers (54/166 vs 1/324, p < 0.001) and females more likely to be on antibiotic prophylaxis (68/324 vs 2/166, p < 0.001). The probability of having urinary symptoms or incontinence decreased up to session 11 (9 months from initial visit). There was slower rate of improvement after session 8 (3 months). Controlling for age, symptoms, and medication use at initial visit, male patients were less likely to report symptom resolution at the time of the last session (OR 0.55, 95% CI 0.33, 0.89). The nadir for reporting symptoms occurred by session 22 for male patients, compared to session 10 for female patients. CONCLUSIONS: Clinical improvement from biofeedback for pediatric patients with dysfunctional voiding may take up to 9 months of therapy, but most cases that improve do so by 3 months. The effect of gender on biofeedback efficacy requires further study, but males may have slower response to biofeedback. Our data provides guidance on when maximum benefit from biofeedback can be expected before considering re-evaluation or other therapies for lower urinary tract symptoms.

Comanagement With Nephrologist Care Is Associated With Fewer Cardiovascular Events Among Liver Transplant Recipients With Chronic Kidney Disease.

Chronic kidney disease (CKD) is associated with cardiovascular (CV) events, a leading complication in liver transplant recipients (LTRs). Timely subspecialty care is associated with improved clinical outcomes in patients with CKD. This study sought to assess associations between nephrology comanagement and CV events among LTRs at risk for or with CKD. METHODS: LTRs with CKD plus those at risk were identified in an inception cohort at a single tertiary care network between 2010 and 2016, using electronic health record data and manual chart review. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or International Classification of Diseases 9th or 10th revision code for CKD and at-risk CKD as estimated glomerular filtration rate 60-89 mL/min/1.73 m2. Cox proportional hazard models assessed the association between nephrology comanagement and CV events among LTRs with or at risk for CKD. RESULTS: Among 602 LTRs followed for up to 6 y posttransplant, prevalence of CKD plus those at risk increased yearly (71% in year 1, 86% in year 6) (P < 0.0001). Rates of nephrology comanagement decreased yearly posttransplant (35% in year 1, 28% in year 6). In multivariable models, nephrology comanagement was associated with lower CV events (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.99). CONCLUSIONS: Among LTRs with CKD, nephrology comanagement may be associated with lower CV events. A prospective study is needed to identify the reasons for improved outcomes and barriers to nephrology referral.

Evaluation of radiomics and machine learning in identification of aggressive tumor features in renal cell carcinoma (RCC).

PURPOSE: The purpose of this study was to evaluate the use of CT radiomics features and machine learning analysis to identify aggressive tumor features, including high nuclear grade (NG) and sarcomatoid (sarc) features, in large renal cell carcinomas (RCCs). METHODS: CT-based volumetric radiomics analysis was performed on non-contrast (NC) and portal venous (PV) phase multidetector computed tomography images of large (> 7 cm) untreated RCCs in 141 patients (46W/95M, mean age 60 years). Machine learning analysis was applied to the extracted radiomics data to evaluate for association with high NG (grade 3-4), with multichannel analysis for NG performed in a subset of patients (n = 80). A similar analysis was performed in a sarcomatoid rich cohort (n = 43, 31M/12F, mean age 63.7 years) using size-matched non-sarcomatoid controls (n = 49) for identification of sarcomatoid change. RESULTS: The XG Boost Model performed best on the tested data. After manual and machine feature extraction, models consisted of 3, 7, 5, 10 radiomics features for NC sarc, PV sarc, NC NG and PV NG, respectively. The area under the receiver operating characteristic curve (AUC) for these models was 0.59, 0.65, 0.69 and 0.58 respectively. The multichannel NG model extracted 6 radiomic features using the feature selection strategy and showed an AUC of 0.67. CONCLUSIONS: Statistically significant but weak associations between aggressive tumor features (high nuclear grade, sarcomatoid features) in large RCC were identified using 3D radiomics and machine learning analysis.

Surgeon Scorecards Improve Muscle Sampling on Transurethral Resection of Bladder Tumor and Recurrence Outcomes in Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: The presence of detrusor muscle is essential for accurate staging of T1 cancers. Detrusor muscle presence can be a quality indicator of transurethral resection of bladder tumor for nonmuscle invasive bladder cancer. We hypothesized that increasing surgeon awareness of personal and institutional detrusor muscle sampling rates could improve resection quality and long-term oncologic outcomes. MATERIALS AND METHODS: A retrospective review of transurethral resections of bladder tumor from 1/2006 to 2/2018 was performed. The presence of detrusor muscle in the pathology report and transurethral resection specimen were extracted from records. Individual surgeon scorecards were created and distributed. Rates of detrusor muscle sampling were compared prior to and 12 months after distribution. Chart review was done to compare 3-year recurrence and progression outcomes before and after distribution of scorecards. RESULTS: The rate of detrusor muscle sampling increased from 36% (1,250/3,488) to 54% (202/373) (p=0.001) in the 12 months after scorecard distribution, ie from 30% (448/1,500) to 55% (91/165) (p <0.001) in Ta tumors and from 47% (183/390) to 72% (42/58) (p <0.001) in T1 tumors. Pathological reporting of muscle also improved for all samples (73%, 2,530/3,488 to 90%, 334/373, p <0.001), Ta (75%, 1,127/1,500 to 94%, 155/165, p <0.001) and T1 (93%, 362/390 to 100%, 58/58, p=0.04). On multivariate Cox regression analysis, the surgeon scorecard was associated with decreased 3-year risk of recurrence (HR 0.63, 95% CI 0.40-0.99). CONCLUSIONS: Creation and distribution of individual surgeon scorecards improved detrusor muscle sampling on transurethral resection and was associated with decreased risk of disease recurrence. Quality evaluation of transurethral resection of bladder tumor may contribute to improved outcomes of patients with nonmuscle invasive bladder cancer.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Identification of Differential Tumor Subtypes of T1 Bladder Cancer.

Stage T1 bladder cancers have the highest progression and recurrence rates of all non-muscle-invasive bladder cancers (NMIBCs). Most T1 cancers are treated with bacillus Calmette-Guérin (BCG), but many will progress or recur, and some T1 patients will die from bladder cancer. Particularly aggressive tumors could be treated with early cystectomy. To better understand the molecular heterogeneity of T1 cancers, we performed transcriptome profiling and unsupervised clustering, and identified five consensus subtypes of T1 tumors treated with repeat transurethral resection (reTUR) and induction and maintenance BCG. The T1-LumGU subtype was associated with carcinoma in situ (CIS; six/13, 46% of all CIS), had high E2F1 and EZH2 expression, and was enriched in E2F target and G2M checkpoint hallmarks. The T1-Inflam subtype was inflamed and infiltrated with immune cells. While most T1 tumors were classified as luminal papillary, the T1-TLum subtype had the highest median luminal papillary score and FGFR3 expression, no recurrence events, and the fewest copy number gains. T1-Myc and T1-Early subtypes had the most recurrences (14/30 within 24 mo), the highest median MYC expression, and, when combined, had significantly worse recurrence-free survival than the other three subtypes. T1-Early had five (38%) recurrences within the first 6 mo of BCG, and repressed IFN-α and IFN-γ hallmarks and inflammation. We developed a single-patient T1 classifier and validated our subtype biology in a second cohort of T1 tumors. Future research will be necessary to validate the proposed T1 subtypes and to determine if therapies can be individualized for each subtype. PATIENT SUMMARY: We identified and characterized expression subtypes of high-grade stage T1 bladder cancer that are biologically heterogeneous and have variable responses to bacillus Calmette-Guérin treatment. We validated the subtypes and describe a single-patient classifier.

Antibody targeting of B7-H4 enhances the immune response in urothelial carcinoma.

Patients with locally advanced and metastatic urothelial carcinoma have a low survival rate (median 15.7 months, 13.1-17.8), with only a 23% response rate to monotherapy treatment with anti-PDL1 checkpoint immunotherapy. To identify new therapeutic targets, we profiled the immune regulatory signatures during murine cancer development using the BBN carcinogen and identified an increase in the expression of the T cell inhibitory protein B7-H4 (VTCN1, B7S1, B7X). B7-H4 expression temporally correlated with decreased lymphocyte infiltration. While the increase in B7-H4 expression within the bladder by CD11b+ monocytes is shared with human cancers, B7-H4 expression has not been previously identified in other murine cancer models. Higher expression of B7-H4 was associated with worse survival in muscle-invasive bladder cancer in humans, and increased B7-H4 expression was identified in luminal and luminal-papillary subtypes of bladder cancer. Evaluation of B7-H4 by single-cell RNA-Seq and immune mass cytometry of human bladder tumors found that B7-H4 is expressed in both the epithelium of urothelial carcinoma and CD68+ macrophages within the tumor. To investigate the function of B7-H4, treatment of human monocyte and T cell co-cultures with a B7-H4 blocking antibody resulted in enhanced IFN-γ secretion by CD4+ and CD8+ T cells. Additionally, anti-B7-H4 antibody treatment of BBN-carcinogen bladder cancers resulted in decreased tumor size, increased CD8+ T cell infiltration within the bladder, and a complimentary decrease in tumor-infiltrating T regulatory cells (Tregs). Furthermore, treatment with a combination of anti-PD-1 and anti-B7-H4 antibodies resulted in a significant reduction in tumor stage, a reduction in tumor size, and an increased level of tumor necrosis. These findings suggest that antibodies targeting B7-H4 may be a viable strategy for bladder cancers unresponsive to PD-1 checkpoint inhibitors.

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia.

Prior studies have investigated sperm retrieval rates in men with nonobstructive azoospermia (NOA) secondary to specific etiologies, yet most cases of NOA are idiopathic. We compared sperm retrieval rates and testicular histopathology in idiopathic NOA (iNOA) and nonidiopathic NOA (niNOA). We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction (microTESE) between 2000 and 2016. Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic. Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology. Among 224 men, 86 (38.4%) were idiopathic, 75 (33.5%) were nonidiopathic, and 63 (28.1%) did not undergo genetic testing. Median age and serum testosterone were higher among iNOA or no testing versus niNOA. Median follicle-stimulating hormone (FSH) was lower among iNOA or no testing versus niNOA. A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele. Sperm retrieval rates were similar between iNOA, niNOA, and no testing (41.8% vs 48.0% vs 55.6%, respectively; P = 0.255). Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA (31.4% and 27.0% vs 16.0%, P = 0.073). On multivariaile analysis, iNOA was not associated with sperm retrieval or spermatogenesis (P = 0.430 and P = 0.078, respectively). Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA. These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.

Oncofertility in adult and pediatric populations: options and barriers.

Cancer and its treatments can affect fertility in a variety of ways, and recent advances in cancer detection and treatment have led to an increasing number of cancer survivors for whom future fertility is a primary concern. Oncofertility is the study of interactions between cancer, anti-cancer therapy, fertility, and reproductive health. Fertility preservation aims to optimize fertility potential before initiation of gonadotoxic therapies. Sperm cryopreservation from an ejaculated sample is the gold standard for adults and post-pubertal adolescents, though added maneuvers such as medical therapy, penile vibratory stimulation, and electroejaculation can be employed when appropriate. When all these approaches fail, testicular sperm extraction can be used to obtain and cryopreserve testicular sperm from the azoospermic patient. Fertility preservation in the pre-pubertal pediatric patient is still experimental, but recent scientific breakthroughs with use of spermatogonial stem cells and testicular tissue transplantation offer great promise for the future. While there may be several practical, cultural, religious, and other barriers to fertility preservation, the establishment of a dedicated fertility preservation team can help to overcome these obstacles and optimize the utilization of fertility preservation in cancer patients of all ages.

Online access to male factor infertility care: the challenge of finding a specialist.

OBJECTIVE: To investigate internet search results available to couples searching for a male factor infertility specialist. DESIGN: Cross-sectional. SETTING: Online search engine. PATIENTS: The phrase "male infertility specialist " was searched in Google for 50 states and Washington D.C. The top 10 results (i.e., first page) of each search were evaluated for website content. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The first page of each search was evaluated for provider type (urology vs. obstetrics and gynecology), level of training (fellowship vs. none), male factor fertility information provided, and procedures offered. We compared search position rank (1-10) to determine the likelihood of finding an urologist versus a practitioner in obstetrics and gynecology. RESULTS: A total of 419 results were identified; the majority were obstetrics and gynecology-related (N = 229, 54.7%). Urology-related results appeared higher than obstetrics and gynecology-related results (median, 4 vs. 5). Andrology fellowship-trained urologists were identified in 153 (36.5%) results. Among 229 obstetrics and gynecology results, 152 unique practices were identified. A small portion (N = 38, 16.6%) of these practices had a fellowship-trained urologist identified on the website. Most obstetrics and gynecology websites did not mention vasectomy reversal (N = 116, 76.3%) or varicocele repair (N = 93, 61.2%). A minority of practices offered referral to urologists for sperm extraction (N = 23, 15.1%) or offered sperm retrieval themselves (N = 23, 15.1%). CONCLUSIONS: When searching online for a male factor infertility specialist, most results identified obstetrics and gynecology physicians. A large proportion of obstetrics and gynecology websites lacked information on male factor fertility treatments and did not offer these treatments. These data indicate the need for a more robust online presence of male reproductive urologists to optimize online access.

Safety and efficacy of radioembolization with glass microspheres in hepatocellular carcinoma patients with elevated lung shunt fraction: analysis of a 103-patient cohort.

BACKGROUND: Technetium-99m macroaggregated albumin is used to estimate lung shunt fraction (LSF) prior to yttrium-90 (Y90). Studies have debated the safety and efficacy of Y90 in patients with LSF > 15%. We aimed to assess the role of Y90 in hepatocellular carcinoma (HCC) with LSF > 15%. METHODS: With IRB approval, we searched our prospectively acquired database of HCC patients with Y90 treated with LSF > 15%. Median LSF and liver and lung doses were calculated. The response was assessed using RECIST. Overall survival (OS) was calculated from date of first Y90. RESULTS: A total of 103 HCC patients underwent Y90. The median baseline LSF was 24.4% (IQR 18.1-28.8). Patients exhibited multifocal disease (59/103, 60%) and median tumor size of 7.85 cm (IQR 5.2, 10.57). BCLC class was A, B, C, and D in 7 (7%), 5 (5%), 85 (83%), and 6 (6%) patients, respectively. The median liver dose was 84.6 Gy (IQR 57.4, 107.55). The median lung dose per session and cumulatively was 22.9 Gy (IQR 15-28) and 29.5 Gy (IQR 20.5-44.3). Thirty-three patients (32%) demonstrated partial response, 57 stable disease, and 13 (13%) had progressive disease. The median OS was 7.3 months (95% CI 5.3, 11.47). Twenty patients (19%) had non-specific pulmonary symptoms (cough, shortness of breath, wheezing) in the 1-year post-Y90. The median time to the appearance of non-specific pulmonary symptoms was 63 days (range 7-224). Thoracic imaging demonstrated no pulmonary fibrosis/injury following treatment in any patient. CONCLUSION: Y90 can be performed in patients with LSF > 15%. The RECIST response was identified in 32% of the patients. In isolation, LSF > 15% should not deter from treatment with Y90.

Contemporary Systematic Review of Health-Related Quality of Life Outcomes in Locoregional Therapies for Hepatocellular Carcinoma.

Health-related quality of life has become an important aspect in oncologic decision making. Recent data suggest that Health-Related Quality of Life (HRQoL) measurements can play an important prognostic role in patients with hepatocellular carcinoma (HCC). Locoregional therapies (LRTs) such as radiofrequency ablation, transarterial chemoembolization, and radioembolization (TARE) are important parts of HCC management. Results demonstrated that radiofrequency ablation treatment results in improving HRQoL compared to surgery for up to 3 years after treatment. Between TARE and transarterial chemoembolization, TARE provides the most benefit in terms of HRQoL. This systematic review investigated contemporary data surrounding HRQoL in patients undergoing LRTs and its impact on clinical decision making.

Prognostic Role of Albumin, Bilirubin, and ALBI Scores: Analysis of 1000 Patients with Hepatocellular Carcinoma Undergoing Radioembolization.

Introduction: We compared the efficacy of the ALBI (albumin-bilirubin) score to the established Child-Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75-6.57); ALBI 3 vs. ALBI 1 was 7.58 (3.89-14.79); and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71-2.43); CP C vs. CP A was 3.27 (2.08-5.14); and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81-3.41); albumin 3 vs. 1 was 4.74 (3.44-6.54); and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82-1.44); bilirubin 3 vs. 1 was 2.37 (1.66-3.40); and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.

Epidemiology and outcomes of hospitalized adults with respiratory syncytial virus: A 6-year retrospective study.

OBJECTIVES: Respiratory syncytial virus (RSV) is an important cause of morbidity and mortality in adults. Existing studies are limited by the number of seasons studied and most have focused on the immunocompromised. METHODS: A retrospective cohort study was conducted on all adults (≥18 years) with a positive RSV molecular test admitted from 2009 to 2015 to one hospital in Chicago, IL. Epidemiologic and outcomes data were collected after IRB approval. RESULTS: Of the 489 eligible patients, 227 had RSV A and 262 had RSV B. Patients had a median age of 61 years and comorbidity (eg, chronic lung disease [40.6%], obesity [37.8%], and cardiac disease [34.3%]). On presentation, most had cough (86.5%), fever (42.4%), and shortness of breath (38.2%). Severe disease was present in 27.6% of patients. Antibiotic was used in 76.3% inpatients and 45.8% at discharged despite few patients (4.7%) having documented bacterial infections. Supplemental oxygen and mechanical ventilation were utilized in 44.6% and 12.3%, respectively, while ICU level care was required in 26.9%. Most patients were discharged home (82.7%). Most deaths (68.4%, 13/19) were attributed to pneumonia or hypoxemia likely from RSV. Most fatal cases were seen in those with recent cancer treatment and older adults. CONCLUSIONS: Respiratory syncytial virus in hospitalized adults is associated with significant morbidity and mortality with 26.9% requiring ICU level care. Antibiotics are commonly prescribed to patients with documented RSV, and antibiotics are frequently continued after diagnosis. Novel antiviral therapies are needed for RSV to improve outcomes and potentially improve antibiotic stewardship in patients without a bacterial infection.

A novel crosslinking protocol stabilizes amyloid ß oligomers capable of inducing Alzheimer's-associated pathologies.

Amyloid ß oligomers (AßOs) accumulate early in Alzheimer's disease (AD) and experimentally cause memory dysfunction and the major pathologies associated with AD, for example, tau abnormalities, synapse loss, oxidative damage, and cognitive dysfunction. In order to develop the most effective AßO-targeting diagnostics and therapeutics, the AßO structures contributing to AD-associated toxicity must be elucidated. Here, we investigate the structural properties and pathogenic relevance of AßOs stabilized by the bifunctional crosslinker 1,5-difluoro-2,4-dinitrobenzene (DFDNB). We find that DFDNB stabilizes synthetic Aß in a soluble oligomeric conformation. With DFDNB, solutions of Aß that would otherwise convert to large aggregates instead yield solutions of stable AßOs, predominantly in the 50-300 kDa range, that are maintained for at least 12 days at 37°C. Structures were determined by biochemical and native top-down mass spectrometry analyses. Assayed in neuronal cultures and i.c.v.-injected mice, the DFDNB-stabilized AßOs were found to induce tau hyperphosphorylation, inhibit choline acetyltransferase, and provoke neuroinflammation. Most interestingly, DFDNB crosslinking was found to stabilize an AßO conformation particularly potent in inducing memory dysfunction in mice. Taken together, these data support the utility of DFDNB crosslinking as a tool for stabilizing pathogenic AßOs in structure-function studies.