While alterations in xenobiotic metabolism are considered causal in the development of bladder cancer (BCa), the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in BCa. This metabolic signature distinguished both normal and benign bladder from BCa. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing BCa from controls, and also non-muscle from muscle-invasive BCa. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in BCa. In particular, we validated tumor-associated hypermethylation in the CYP1A1 and CYP1B1 promoters of BCa tissues by bisulfite sequence analysis and methylation-specific PCR, and also by in vitro treatment of T-24 BCa cell line with the DNA demethylating agent 5-aza-2′-deoxycytidine. Further, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of BCa specimens compared to matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of BCa, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

Patients who undergo PTA may be at increased risk for RF. After comparing patient and donor demographics, IS, and human leukocyte antigen mismatch, it seems that PTA is an independent risk factor for the development of renal failure. Patients with more successful pancreatic grafts demonstrated lower eGFR. Patients should be made aware of the risks of long-term IS. Only the most appropriate patients should be chosen for PTA.

Community partnered participatory research (CPPR) emphasizes community engagement, respect, and empowerment as guiding principles to promote mental health equity. This article describes the "Vision" stage of a CPPR-informed model to implement evidence-based practices for depression in two African American churches in Harlem, New York. Essential parts of the Vision include engagement of stakeholders and collaborative planning. The engagement process increased awareness about the project via a community-focused mental health symposium. The collaborative planning stage resulted in creating a multi-disciplinary Community Coalition for Mental Health, establishing the Coalition's values, agreeing to change the initial chosen study intervention from Interpersonal Counseling to Mental Health First Aid, and developing a website to disseminate the group's work. Key lessons learned from our partnered process are: 1) support from the lead pastor is crucial; 2) balancing community and academic interests can be challenging; 3) icebreaker activities foster relationships and reinforce CPPR principles; 4) multiple communication channels can enhance community participation; and, 5) should organize data in ways that make them easier to interpret.

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The development of effective treatment strategies to provide durable control of isolated diffuse metastases to the liver is a major challenge in clinical oncology. The number of patients afflicted annually with isolated liver metastases is considerable; of the 156,000 patients diagnosed with colorectal cancer in 2009, it is estimated that up to 40,000 will develop liver metastases as the sole or dominant site of disease progression and of whom only 10% to 20% will have tumors amenable to resection. Patients with neuroendocrine cancers and ocular melanoma will frequently develop isolated and diffuse liver metastases as the dominant mode of tumor metastasis and, although less frequent, patients with other types of cancers such as cutaneous melanoma or breast cancer can occasionally develop isolated diffuse metastases to the liver.Isolated hepatic perfusion and percutaneous hepatic perfusion are under clinical evaluation for patients with diffuse isolated liver metastases from various solid organ cancers. Both share the advantages of intensifying treatment to the cancer-burdened organ of the body to improve efficacy and limit unnecessary systemic toxicity by selectively delivering high-dose therapeutic agents into the hepatic arterial system from which established metastases derive their predominant blood supply. In this article, we will review the history and early clinical development of isolated perfusion, the techniques of isolated hepatic perfusion and percutaneous hepatic perfusion, the current clinical results with isolation perfusion, and discuss the potential future clinical use of these approaches.

Background Morbid obesity is usually accompanied by both subcutaneous and visceral fat accumulation. Fat can mimic an air bag, absorbing the force of a collision. We hypothesized that morbid obesity is mechanically protective for hollow viscus organs in blunt abdominal trauma (BAT). Methods The National Trauma Data Bank (NTDB) was queried for BAT patients from 2013 to 2015. We looked at the rate of gastrointestinal (GI) tract injuries in all BAT patients with different BMIs. A subset analysis of BAT patients with operative GI tract injuries was performed to evaluate the need for abdominal operation. Multivariate analyses were carried out to identify factors independently associated with increased GI tract injuries and associated abdominal operations. Results A total of 100,459 BAT patients were evaluated in the NTDB. Patients with GI tract injury had a lower proportion of morbidly obese patients [body weight index (BMI) C 40 kg/m2)] (3.7% vs. 4.2%, p = 0.015) and instead had more underweight patients (BMI \ 18.5) (5.9% vs. 5.0%, p \ 0.001). The risk of GI tract injury decreased 11.6% independently in morbidly obese patients and increased 15.7% in underweight patients. Of the patients with GI tract injuries (N = 11,467), patients who needed a GI operation had a significantly lower proportion of morbidly obese patients (3.2% vs. 5.3%, p \ 0.001). The risk of abdominal operation for GI tract injury decreased 57.3% independently in morbidly obese patients. Compared with underweight patients, morbidly obese patients had significantly less GI tract injury (6.0% vs. 13.3%, p \ 0.001) and associated abdominal operation rates (65.2% vs. 73.3%, p \ 0.001). Conclusion Obesity is protective in BAT. This translates into lower rates of GI tract injury and operation in morbidly obese patients. In contrast, underweight patients appear to suffer a higher rate of GI tract injury and associated GI operations.

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BACKGROUND The recognition of the relationship between volume and outcomes led to the regionalization of trauma care. The relationship between trauma mechanism-subtype and outcomes has yet to be explored. We hypothesized that trauma centers with a high volume of penetrating trauma patients might be associated with a higher survival rate for penetrating trauma patients. METHODS A retrospective cohort analysis of penetrating trauma patients presenting between 2011 and 2015 was conducted using the National Trauma Database and the trauma registry at the Stroger Cook County Hospital. Linear regression was used to determine the relationship between mortality and the annual volume of penetrating trauma seen by the treating hospital. RESULTS Nationally, penetrating injuries account for 9.5% of the trauma cases treated. Patients treated within the top quartile penetrating-volume hospitals (≥167 penetrating cases per annum) are more severely injured (Injury Severity Score: 8.9 vs. 7.7) than those treated at the lowest quartile penetrating volume centers (<36.6 patients per annum). There was a lower mortality rate at institutions that treated high numbers of penetrating trauma patients per annum. A penetrating trauma mortality risk adjustment model showed that the volume of penetrating trauma patients was an independent factor associated with survival rate. CONCLUSION Trauma centers with high penetrating trauma patient volumes are associated with improved survival of these patients. This association with improved survival does not hold true for the total trauma volume at a center but is specific to the volume of the penetrating trauma subtype. LEVEL OF EVIDENCE Prognostic/Epidemiology Study, Level-III; Therapeutic/Care Management, Level IV.