Current Treatment and Outcomes Benchmark for Locally Advanced or Metastatic Urothelial Cancer From a Large UK-Based Single Centre

Objectives: To characterize treatment patterns and survival outcomes for patients with locally advanced or metastatic malignancy of the urothelial tract during a period immediately preceding the widespread use of immune checkpoint inhibitors in the UK. Patients and Methods: We retrospectively examined the electronic case notes of patients attending the Leeds Cancer Center, UK with locally advanced or metastatic urothelial carcinoma, receiving chemotherapy between January 2003 and March 2017. Patient characteristics, treatment patterns, and outcomes were collected. Summary and descriptive statistics were calculated for categorical and continuous variables as appropriate. The Kaplan–Meier method was used to estimate median survival and Cox regression proportional hazards model was used to explore relationships between clinical variables and outcome. Results: Two hundred and sixteen patients made up the study cohort, with a median age of 66 years (range: 35–83) and 72.7% being male. First-line treatment consisted of either a cisplatin- (44%) or carboplatin-based regimen (48%) in the majority of patients. Twenty seven percent of patients received a second-line of treatment (most commonly single-agent paclitaxel) following a first-line platinum containing regimen. Grade 4 neutropenia was observed in 19 and 27% of those treated with a first-line cisplatin- and carboplatin-based regimen, respectively. The median overall survival (mOS) of the study cohort was estimated to be 16.2 months (IQR: 10.6–28.3 months). Receipt by patients of cisplatin-based chemotherapy was associated with a longer mOS and this association persisted when survival analysis was adjusted for age, sex, performance status and presence of distant metastases. Conclusions: This study provides a useful benchmark for outcomes achieved in a real-world setting for patients with locally advanced or metastatic UC treated with chemotherapy in the immediate pre-immunotherapy era

Risk of hospitalization and death following prostate biopsy in Scotland

OBJECTIVE: To investigate the risk of hospitalization and death following prostate biopsy. STUDY DESIGN: Retrospective cohort study. METHODS: Our study population comprised 10,285 patients with a record of first ever prostate biopsy between 2009 and 2013 on computerized acute hospital discharge or outpatient records covering Scotland. Using the general population as a comparison group, expected numbers of admissions/deaths were derived by applying age-, sex-, deprivation category-, and calendar year-specific rates of hospital admissions/deaths to the study population. Indirectly standardized hospital admission ratios (SHRs) and mortality ratios (SMRs) were calculated by dividing the observed numbers of admissions/deaths by expected numbers. RESULTS: Compared with background rates, patients were more likely to be admitted to hospital within 30 days (SHR 2.7; 95% confidence interval 2.4, 2.9) and 120 days (SHR 4.0; 3.8, 4.1) of biopsy. Patients with prior co-morbidity had higher SHRs. The risk of death within 30 days of biopsy was not increased significantly (SMR 1.6; 0.9, 2.7), but within 120 days, the risk of death was significantly higher than expected (SMR 1.9; 1.5, 2.4). The risk of death increased with age and tended to be higher among patients with prior co-morbidity. Overall risks of hospitalization and of death up to 120 days were increased both in men diagnosed and those not diagnosed with prostate cancer. CONCLUSIONS: Higher rates of adverse events in older patients and patients with prior co-morbidity emphasizes the need for careful patient selection for prostate biopsy and justifies ongoing efforts to minimize the risk of complications

Deaths from heart failure: using coarsened exact matching to correct cause-of-death statistics

<p>Abstract</p> <p>Background</p> <p>Incomplete information on death certificates makes recorded cause-of-death data less useful for public health monitoring and planning. Certifying physicians sometimes list only the mode of death without indicating the underlying disease or diseases that led to the death. Inconsistent cause-of-death assignment among cardiovascular causes of death is of particular concern. This can prevent valid epidemiologic comparisons across countries and over time.</p> <p>Methods</p> <p>We propose that coarsened exact matching be used to infer the underlying causes of death where only the mode of death is known. We focus on the case of heart failure in US, Mexican, and Brazilian death records.</p> <p>Results</p> <p>Redistribution algorithms derived using this method assign the largest proportion of heart failure deaths to ischemic heart disease in all three countries (53%, 26%, and 22% respectively), with larger proportions assigned to hypertensive heart disease and diabetes in Mexico and Brazil (16% and 23% vs. 7% for hypertensive heart disease, and 13% and 9% vs. 6% for diabetes). Reassigning these heart failure deaths increases the US ischemic heart disease mortality rate by 6%.</p> <p>Conclusions</p> <p>The frequency with which physicians list heart failure in the causal chain for various underlying causes of death allows for inference about how physicians use heart failure on the death certificate in different settings. This easy-to-use method has the potential to reduce bias and increase comparability in cause-of-death data, thereby improving the public health utility of death records.</p

The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-de-pendent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist. CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages

Non-invasive or minimally invasive autopsy compared to conventional autopsy of suspected natural deaths in adults: a systematic review

Objectives: Autopsies are used for healthcare quality control and improving medical knowledge. Because autopsy rates are declining worldwide, various non-invasive or minimally invasive autopsy methods are now being developed. To investigate whether these might replace the invasive autopsies conventionally performed in naturally deceased adults, we systematically reviewed original prospective validation studies. Materials and methods: We searched six databases. Two reviewers independently selected articles and extracted data. Methods and patient groups were too heterogeneous for meaningful meta-analysis of outcomes. Results: Sixteen of 1538 articles met our inclusion criteria. Eight studies used a blinded comparison; ten included less than 30 appropriate cases. Thirteen studies used radiological imaging (seven dealt solely with non-invasive procedures), two thoracoscopy and laparoscopy, and one sampling without imaging. Combining CT and MR was the best non-invasive method (agreement for cause of death: 70 %, 95%CI: 62.6; 76.4), but minimally invasive methods surpassed non-invasive methods. The highest sensitivity for cause of death (90.9 %, 95%CI: 74.5; 97.6, suspected duplicates excluded) was achieved in recent studies combining CT, CT-angiography and biopsies. Conclusion: Minimally invasive autopsies including biopsies performed best. To establish a feasible alternative to conventional autopsy and to increase consent to post-mortem investigations, further research in larger study groups is needed. Key points: • Health care quality control benefits from clinical feedback provided by (alternative) autopsies. • So far, sixteen studies investigated alternative autopsy methods for naturally deceased adults. • Thirteen studies used radiological imaging modalities, eight tissue biopsies, and three CT-angiography. • Combined CT, CT-angiography and biopsies were most sensitive diagnosing cause of death