National Institutes of Health Clinical Research Funding and All-Cause In-Hospital Traumatic Brain Injury-Related Mortality.

Introduction Higher federal research funding levels may improve patient outcomes. We examined this relationship between traumatic brain injury (TBI) funding and all-cause in-hospital TBI-related mortality. Methods Using an ecological series analysis, we examined the linear trend in both clinical TBI research funding in year 2000 United States dollars ($) (National Institutes of Health [NIH] RePORTER) and in-hospital isolated TBI mortality among patients aged 15 and older (National Trauma Data Bank [NTDB], TBI-related ICD-9 or ICD-10 code, abbreviated head injury score >2 and body region score <2 with ICU admission) between 2007-2015 with data from centers contributing all years of data for the study period. Linear regression was used to assess the relationship between mortality rate and total funding, lagged one to three years, both overall and within ten-year age groups. Results The mean annual NIH-TBI research funding was $64.36 million (lowest: 2008; $48.79 million, highest: 2015; $71.42 million). 192,597 encounters of patients 15 years and older, predominantly male (67.5%) and with polytrauma (59.9%), were included. There was no statistically significant reduction in in-hospital TBI-related mortality (14.15% in 2007 to 13.36% in 2015) for the cohort overall, but the mortality rate decreased for patients over 55 years. The greatest mortality reduction occurred in patients 85 years and older (-62.35, 95% CI -92.45-32.25), followed by patients 75-84 years (-44.41, 95% CI -61.72, -27.09), patients 65-74 years (-47.60, 95% CI -67.39, -27.81), and patients 55-64 years of age (-15.15, 95% CI -27.59, -2.72). During the study period, annual NIH funding for TBI varied from the lowest level of $48.79 million (in 2007) to the highest level of $77.34.43 million (in 2005). There was no association between funding in the previous three years and the in-hospital TBI-related mortality rate. Conclusion This study found a variable pattern in NIH funding for clinical TBI research and a contemporaneous reduction in moderate-severe TBI-related deaths only for those aged 55 years and older, but no association between funding and mortality.

Correction: National Institutes of Health Clinical Research Funding and All-Cause In-Hospital Traumatic Brain Injury-Related Mortality.

[This corrects the article DOI: 10.7759/cureus.27228.].

Screening of Early and Late Onset Alzheimer's Disease Genetic Risk Factors in a Cohort of Dementia Patients from Liguria, Italy.

Cohorts from a defined geographical area enable ad hoc genotype-phenotype correlation studies providing novel and unique insight into disease. We analysed genetic risk factors associated with early and late onset Alzheimer's disease (EOAD and LOAD) in a population from Liguria (northern Italy), as part of an ongoing longitudinal study. We screened 37 AD, 8 mild cognitive impairment (MCI), 3 AD and CVD (cerebrovascular disease), 3 MCI and CVD, 8 frontotemporal dementia (FTD) and 2 progressive supranuclear palsy (PSP) patients, and 28 normal controls (NCs).We sequenced PSEN1, PSEN2 and APP (EOAD risk factors), as well as MAPT, GRN and TARDBP for all cases and NCs, and analysed the APOE, CLU, CR1 and PICALM genotypes as well as the MAPT and ACE haplotypes (LOAD risk factors) for the AD (n = 37) and AD + MCI (n = 45) cases and NCs (n = 28).We identified variants in PSEN1, PSEN2 and TARDBP across a range of phenotypes (AD, AD and CVD, FTD and PSP), suggesting that screening of all known candidate genes of Alzheimer's and non-Alzheimer's forms of dementias in all dementia cases might be warranted. The analysis of the LOAD risk factors revealed no association with AD or AD + MCI status after Bonferroni correction. Lack of association with APOE is supported by previous studies in the Italian population. Our data also evidenced: 1) a potentially protective haplotype at the PSEN2 locus; 2) a nominal association with the GWAS-risk allele A for rs3818361 in CR1 and; 3) a threefold prevalence of AD in the female population compared to men.Our results will need to be further assessed and confirmed in larger cohorts from this area.

Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma.

Human kidney injury molecule-1 (hKIM-1) is a type 1 transmembrane protein that is not detectable in normal kidney tissue but is expressed at high levels in human and rodent kidneys with dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury. Therefore, it was hypothesized that renal tumors express hKIM-1 and release this protein into the urine. Forty renal cell carcinoma (RCC) and 484 nonrenal tumors were analyzed by immunohistochemistry for expression of hKIM-1 (group 1). Urine samples before nephrectomy and nephrectomy tissue samples were collected from an additional 42 patients with renal tumors, from 30 normal control subjects, and also from 10 patients with prostate carcinoma (group 2). In five additional patients with RCC, urine was collected before and after nephrectomy (group 3). Tissue was examined for expression of hKIM-1, and cell-free urine supernatants were analyzed for hKIM-1 by ELISA. Urinary hKIM-1 was normalized to the urinary creatinine concentration (U(Cr)). Expression of hKIM-1 was present in 32 tissue sections (91%) of 35 clear cell RCC (group 1). In group 2, the normalized urinary hKIM-1 levels were significantly higher in patients with clear cell RCC (0.39 +/- 0.08 ng/mg U(Cr); n = 21), compared with levels in patients with prostate carcinoma (0.12 +/- 0.03 ng/mg U(Cr); P < 0.02; n = 10), or normal control subjects (0.05 +/- 0.01 ng/mg U(Cr); P < 0.005; n = 30). Tissue sections from 28 (82%) of 34 primary RCC stained positively for the expression of hKIM-1. In all patients with a detectable prenephrectomy urinary hKIM-1 level, there was either complete disappearance or marked reduction after nephrectomy (group 3). In conclusion, the cleaved ectodomain of hKIM-1 can be detected in the urine of patients with RCC and may serve as a new biomarker for early detection of RCC.