• Other research productsclose
• 2013-2022close
• National Institutes of Health close
• NIH|NATIONAL_CENTER_FOR_ADVANCING_TRANSLATIONAL_SCIENCES close
• US close

IntroductionAcute kidney injury (AKI) affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC) is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates) was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short-term outcomes.Methods and analysisThe NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions in 4 countries (USA, Canada, Australia, and India). A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™) that captured all NICU admissions from 1/1/14 to 3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with a low likelihood of AKI. Data collection included: (1) baseline demographic information; (2) daily physiologic parameters and care received during the first week of life; (3) weekly “snapshots”; (4) discharge information including growth parameters, final diagnoses, discharge medications, and need for renal replacement therapy; and (5) all serum creatinine values.Ethics and disseminationAWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences.DiscussionThe purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions, and a few “lessons learned.” The AWAKEN database includes ~325 unique variables and >4 million discrete data points. AWAKEN will be the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during hospitalization. The AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health, and well-being of newborns at risk for kidney disease.

Vitamin E has been the subject of numerous basic and clinical research studies for cancer chemoprevention, which have shown widely varying results. At present, the NIH Office of Dietary Supplements does not consider there to be sufficient evidence for the use of Vitamin E supplementation for cancer prevention. The heterogeneous nature of Vitamin E and the differences in the anti-cancer activities of its components suggests that the study of individual tocopherols may yield more definitive and encouraging results. Bladder cancer (BCa) presents an ideal opportunity for the evaluation of tocopherols as novel chemopreventive agents. While a majority of newly diagnosed BCa cases are localized and confined to the initiation site on the interior urothelial lining, the high rate of recurrence necessitates long-term follow-up and increases the need for novel agents that can prevent new tumor initiation. As natural products already present in the diet, with a known safety profile, tocopherols are excellent candidates for application as dietary chemopreventive agents to reduce the recurrence rate of BCa and improve treatment outcomes. In this study, I demonstrate that delta-tocopherol is more effective than either of the more common alpha- or gamma- tocopherols at inducing apoptosis in human BCa cell lines. I identified the cause of this effect to be induction of endoplasmic reticulum (ER) stress and the unfolded protein response, leading to death receptor 5 mediated apoptosis. Additionally, delta tocopherol treated cells exhibited an autophagy-like phenotype which, when investigated further, provided novel evidence of endoplasmic reticulum specific, ER stress-related autophagy that remains an emerging field of study. Both xenograft and transgenic mouse studies have confirmed the strong anti-tumor and anti-tumorigenesis efficacy of dietary delta tocopherol administration both at the primary tumor initiation site and at distant sites, with no observed negative side effects. As the first study of delta tocopherol as an individual chemopreventive agent in BCa, these results suggest strong potential for the future development and clinical application of dietary delta tocopherol supplementation to improve the lives and treatment outcomes of BCa patients.

Background: Nearly 30,000 patients with coronavirus disease-2019 (COVID-19) have been hospitalized in New York City as of April 14th, 2020. Data on the epidemiology, clinical course, and outcomes of critically ill patients with COVID-19 in this setting are needed. Methods: We prospectively collected clinical, biomarker, and treatment data on critically ill adults with laboratory-confirmed-COVID-19 admitted to two hospitals in northern Manhattan between March 2nd and April 1st, 2020. The primary outcome was in-hospital mortality. Secondary outcomes included frequency and duration of invasive mechanical ventilation, frequency of vasopressor use and renal-replacement-therapy, and time to clinical deterioration following hospital admission. The relationship between clinical risk factors, biomarkers, and in-hospital mortality was modeled using Cox-proportional-hazards regression. Each patient had at least 14 days of observation. Results: Of 1,150 adults hospitalized with COVID-19 during the study period, 257 (22%) were critically ill. The median age was 62 years (interquartile range [IQR] 51-72); 170 (66%) were male. Two-hundred twelve (82%) had at least one chronic illness, the most common of which were hypertension (63%; 162/257) and diabetes mellitus (36%; 92/257). One-hundred-thirty-eight patients (54%) were obese, and 13 (5%) were healthcare workers. As of April 14th, 2020, in-hospital mortality was 33% (86/257); 47% (122/257) of patients remained hospitalized. Two-hundred-one (79%) patients received invasive mechanical ventilation (median 13 days [IQR 9-17]), and 54% (138/257) and 29% (75/257) required vasopressors and renal-replacement-therapy, respectively. The median time to clinical deterioration following hospital admission was 3 days (IQR 1-6). Older age, hypertension, chronic lung disease, and higher concentrations of interleukin-6 and d-dimer at admission were independently associated with in-hospital mortality. Conclusions: Critical illness among patients hospitalized with COVID-19 in New York City is common and associated with a high frequency of invasive mechanical ventilation, extra-pulmonary organ dysfunction, and substantial in-hospital mortality.

The Epidemiology and Development of Alzheimer’s Disease in Urban and Rural Costa Rica research project is a longitudinal study of memory and aging harmonized with the University of Kansas’ Alzheimer Disease Center (ADC). This is the first paperless ADC based entirely in the REDCap database. The investigators developed a parallel assessment toolkit/battery in Spanish and deployed it in San Jose and Guanacaste Costa Rica. To meet the needs of Latin American colleagues, the assessment battery was migrated to Colectica and then redeveloped using QueXF, so that all data forms could be optically character recognized. The investigators will review the hurdles and plans for the next steps of development.