Citations

Abstract Background: Melanoma cases may exist in pancreatic cancer kindreds, whereas there is increased risk of pancreatic cancer in familial melanoma. The two cancers may share genetic susceptibility variants in common. Methods: Three dbGaP (datasets in Genotypes and Phenotypes)-deposited GWAS (genome-wide association study) datasets (MD Anderson melanoma, PanScan 1, and PanScan 2 for pancreatic cancer) were used. Thirty-seven melanoma susceptibility variants in 22 genomic regions from published GWAS, plus melanoma-related genes and pathways were examined for pancreatic cancer risk in the PanScan datasets. Conversely, nine known pancreatic cancer susceptibility variants were examined for melanoma risk in the MD Anderson dataset. Results: In the PanScan data, initial associations were found with melanoma susceptibility variants in NCOA6 [rs4911442; OR, 1.32; 95% confidence interval (CI), 1.03–1.70; P = 0.03], YWHAZP5 (rs17119461; OR, 2.62; 95% CI, 1.08–6.35; P = 0.03), and YWHAZP5 (rs17119490; OR, 2.62; 95% CI, 1.08–6.34; P = 0.03), TYRP1 (P = 0.04), and IFNA13 (P = 0.04). In the melanoma dataset, two pancreatic cancer susceptibility variants were associated: NR5A2 (rs12029406; OR, 1.39; 95% CI, 1.01–1.92; P = 0.04) and CLPTM1L-TERT (rs401681; OR, 1.16; 95% CI, 1.01–1.34; P = 0.04). None of these associations remained significant after correcting for multiple comparisons. Conclusion: Reported variants of melanoma genes and pathways do not play a role in pancreatic cancer predisposition. Reciprocally, pancreatic cancer susceptibility variants are not associated with melanoma risk. Impact: Known melanoma-related genes and pathways, as well as GWAS-derived susceptibility variants of melanoma and pancreatic cancer, do not explain the shared genetic etiology of these two cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1121–4. ©2014 AACR.

We compared the results of percutaneous in situ arthrodesis with open arthrodesis of the distal interphalangeal joint with a headless compression screw. In the percutaneous in situ arthrodesis group (17 joints), the screw was inserted from the fingertip across the unprepared joint. In the open group (12 joints), flat cancellous surfaces were prepared before screw insertion. Solid fusion was found in 10/17 joints (59%) with percutaneous in situ arthrodesis and in 11/12 joints (92%) with open arthrodesis. Among the other seven joints with percutaneous in situ arthrodesis, six had fibrous union and were asymptomatic at a mean of 18 months, and one failed, requiring revision. One joint with open arthrodesis had fibrous union and was asymptomatic 12 months after surgery. We conclude that open arthrodesis is better than the percutaneous method, as a greater percentage achieve bone union. The open approach allows osteophyte removal and slightly better correction of angular deformity in the coronal plane.

The pathologic substrate of the clinical syndrome of dementia with Lewy bodies (DLB) remains to be determined. Only a few prospective clinicopathologic studies have been reported. In those reports, most cases of DLB had neocortical or limbic Lewy bodies and Alzheimer-type pathology below threshold for diagnosis of Alzheimer's disease. These results are in accord with recent retrospective clinicopathologic studies of dementia occurring in Parkinson's disease, in which cortical Lewy bodies, rather than concurrent Alzheimer's disease, are increasingly recognized as the pathologic substrate of dementia. Additional clinicopathologic studies are warranted to address the role of other Lewy-related pathology, most notably Lewy neurites, in the cognitive impairment of DLB. (J Geriatr Psychiatry Neurol 2002; 15:000–000).

Progressive supranuclear palsy (PSP) is, after Parkinson's disease, the most common form of degenerative parkinsonism. Several clinical features are used in the recognition of this disorder as well as in the differentiation from related disorders. Clinical criteria that could increase diagnostic accuracy in research studies are also emphasized. Due to a better understanding of the genetic aspects of PSP, recent studies have suggested that it is a recessive disorder in linkage disequilibrium with the tau (τ) gene, rather than a sporadic disorder. In addition, the recent identification of mutations in the τ gene associated with a similar neurodegenerative condition (frontotemporal dementia and parkinsonism linked to chromosome 17) has further strengthened the argument that τ dysfunction is somehow involved in the pathogenesis of PSP. Nongenetic factors that could trigger or perpetuate the cascade of events leading to neuronal degeneration in PSP are also reviewed.

Fourteen patients who had cognitive dysfunction were studied with quantitative electroencephalography (EEG), singlephoton emission computed tomography (SPECT), and several tests of intellectual and memory function, including the Wechsler Adult Intelligence Scale (WAIS), the Auditory Verbal Learning Test, and the Short Test of Mental Status, to determine whether EEG background frequency content correlates with degree of dementia and with regional uptake of radioisotope on SPECT. The factors from spectral analysis that correlated best with psychometric data were mean frequency in the 1.5– to 20-Hz range and percentage power in the 13- to 20-Hz band (positive correlation) or the 1.5- to 8-Hz band (negative correlation). The WAIS subtest scores that correlated most with the EEG data were performance IQ and perceptual organization. Correlations between percentage power and amplitude ratio in the EEG frequency bands and regional SPECT counts were found, but most were not statistically significant. ( J Geriatr Psychiatry Neurol 1992;5:22–30).

The purpose of this case is to describe the complex perioperative management of a 30-year-old woman with congenital heart disease and multiple resternotomies presenting with pulmonary homograft dysfunction and evaluation for percutaneous pulmonary valve replacement. Transvenous, transcatheter Melody valve placement caused left main coronary artery occlusion and cardiogenic shock. An Impella ventricular assist device (VAD) provided rescue therapy during operating room transport for valve removal and pulmonary homograft replacement. ECMO support was required following surgery. Several days later during an attempted ECMO wean, her hemodynamics deteriorated abruptly. Transesophageal and epicardial echocardiography identified pulmonary graft obstruction, requiring homograft revision due to large thrombosis. This case illustrates a role for Impella VAD as bridge to definitive procedure after left coronary occlusion and describes management of complex perioperative ECMO support challenges.

ABSTRACTBackground and ObjectiveThe aims of the present study were to investigate the thermal‐dose dependent effect of heat stress on hepatocyte and HCC cell death mechanisms using clinically relevant experimental heat stress conditions in vitro and to investigate apoptotic cell death induced by laser thermal ablation in vivo.Study Design/Materials and MethodsInstitutional Animal Care and Use Committee approved all studies. Hepatocyte and HCC cell lines were heat stressed from 37 to 60°C for 2 or 10 minutes and assessed for viability, cytotoxicity and caspase‐3/7 activity at 6 and/or 24 hours post‐treatment (N = 3). Viability experiments were repeated with the RIPK1 inhibitor Necrostatin‐1 to block necroptosis (N = 3). Rats with orthotopic HCC tumors stably expressing luciferase (N1S1luc2) were randomized to US‐guided laser ablation (3W‐45s for an intentional partial ablation; N = 6) or sham (N = 6) and followed by post‐ablation caspase‐3/7 bioluminescence imaging at 6 and 24 hours and cleaved caspase‐3 immunostaining. P < 0.05 was considered statistically significant.ResultsHeat‐stress induced apoptosis and necrosis in hepatocytes and HCC cells in a thermal dose and cell‐type dependent manner. Inhibition of RIPIK1‐mediated necroptosis induced a significant, differential increase in HCC cell viability under physiologic and hyperthermic heat stress (P < 0.001). Intentional partial laser thermal ablation induced a significant increase in caspase‐3/7 activity in the laser versus sham ablation groups at both 6 hours (10.1‐fold, P < 0.01) and 24 hours (16.7‐fold, P < 0.02). Immunohistochemistry confirmed increased cleaved caspase‐3 staining at the tumor ablation margin 24 hours post‐ablation.ConclusionsBoth regulated and non‐regulated cell death mechanisms mediate heat stress‐induced HCC cell killing and vary between hepatocytes and HCC subtypes. Apoptosis is a significant mechanism of cell death at the HCC tumor ablation margin. Lasers Surg. Med. 46:290–301, 2014. © 2014 Wiley Periodicals, Inc.

BACKGROUNDTo ensure that National Institutes of Health‐funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer Institute (NCI) cancer centers' clinical research programs is reported to the NCI.METHODSEMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets.RESULTSCancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers.CONCLUSIONSCatchment area definitions and the collection of patient‐level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States. Cancer 2014;120(7 suppl):1113–21. © 2014 American Cancer Society.

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines.