ObjectivesTo describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. Patients and methodsUsing Surveillance, Epidemiology, and End Results-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. ResultsOver the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N + , or M + disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder-sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. ConclusionsPalliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in diseasespecific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician-, patient-, and system-level barriers to this care.Keywords urinary bladder neoplasms, palliative care, palliative medicine, cystectomy, quality of health care, health services research, Medicare, #BladderCancer, #blcsm

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IL-7 signaling is required for thymocyte development and its loss has a severe deleterious effect on thymus function. Thymocyte-stromal cell interactions and other mechanisms tightly regulate IL-7 expression. We show that disruption of that regulation by over-expression of IL-7 inhibits T-cell development and promotes extensive B-cell lymphopoiesis in the thymus. Our data reveal that high levels of IL-7 negate Notch-1 function in thymocytes found in IL-7 transgenic mice and in co-culture with OP9-DL1 cells. While high levels of IL-7R are present on thymocytes, increased suppressor of cytokine signaling-1 expression blunts IL-7 downstream signaling, resulting in hypo-phosphorylation of proteins in the PI3K-Akt pathway. Consequently, GSK3β remains active and inhibits Notch-1 signaling as observed by decreased Hes-1 and Deltex expression in thymic progenitors. This is the first demonstration that high levels of IL-7 antagonize Notch-1 signaling and suggest that IL-7 may affect T- versus B-lineage choice in the thymus.

ARTICLE INFO ______________________________________________________________ ______________________Purpose: The incidence of lower urinary tract symptoms (LUTS) as the sole presenting symptom for bladder cancer has traditionally been reported to be low. The objective of this study was to evaluate the prevalence and clinical characteristics of newly diagnosed bladder cancer patients who presented with LUTS in the absence of gross or microscopic hematuria. Materials and Methods:We queried our database of bladder cancer patients at the Atlanta Veteran's Affairs Medical Center (AVAMC) to identify patients who presented solely with LUTS and were subsequently diagnosed with bladder cancer. Demographic, clinical, and pathologic variables were examined. Results: 4.1% (14/340) of bladder cancer patients in our series presented solely with LUTS. Mean age and Charlson Co-morbidity Index of these patients was 66.4 years (range = 52-83) and 3 (range = 0-7), respectively. Of the 14 patients in our cohort presenting with LUTS, 9 (64.3%), 4 (28.6%), and 1 (7.1%) patients presented with clinical stage Ta, carcinoma in Situ (CIS), and T2 disease. At a median follow-up of 3.79 years, recurrence occurred in 7 (50.0%) patients with progression occurring in 1 (7.1%) patient. 11 (78.6%) patients were alive and currently disease free, and 3 (21.4%) patients had died, with only one (7.1%) death attributable to bladder cancer. Conclusions: Our database shows a 4.1% incidence of LUTS as the sole presenting symptom in patients with newly diagnosed bladder cancer. This study suggests that urologists should have a low threshold for evaluating patients with unexplained LUTS for underlying bladder cancer.

Key Points Question What is the comparative effectiveness of first-line targeted therapy, immunotherapy, and combination therapy in a real-world cohort of patients with metastatic clear cell renal cell carcinoma? Findings In this propensity-matched cohort study of 5872 patients treated in real-world clinical practice, first-line immunotherapy and combination therapy were associated with improved overall survival compared with first-line targeted therapy. Meaning This study suggests that clinical trial findings demonstrating an overall survival benefit associated with first-line immunotherapy-based regimens compared with targeted therapy are generalizable to a broader population of patients.