Diagnostic Patterns and Immunohistochemical Stain Usage in Extended Core Prostate Biopsies: Comparisons Between Genitourinary and Non-Genitourinary Pathologists

Background: Ancillary immunohistochemical (IPOX) stains are useful in clarifying diagnostically challenging pathologic specimens. In diagnostic workup of prostate needle biopsies, stains for basal cells and α-methylacyl coenzyme A racemase are routinely used to support or refute the diagnosis of prostate cancer. Although useful, these stains add cost and must be used judiciously. There is a lack of firm guidelines establishing the proper utilization of IPOX studies in prostate pathology. Therefore, differences in patterns of stain use and diagnoses may exist, related to expertise of the pathologist. Objectives: The purpose of this study was to compare patterns of diagnoses and IPOX stain use in extended core prostate biopsies between genitourinary (GU) and non-genitourinary (NGU) pathologists in the University of Massachusetts Medical Center Pathology department. Methods: By computer search of medical records, consecutive extended core prostate biopsies (6+ cores) from years 2006-2011 were identified. Using Current Procedural Terminology (CPT) billing data, the number of cores and number of IPOX stains were retrieved. Diagnoses were recorded. Pathologists were divided into two groups based on expertise: genitourinary and non-genitourinary. Differences in the patterns of IPOX use and diagnoses between the two groups were analyzed. Results: GU pathologists diagnose significantly higher rates of prostate cancer (43.8% vs. 35.8%, p Conclusion: Significant differences exist in patterns of IPOX usage between GU and NGU pathologists in extended core prostate biopsy in this single institution study. This suggests the need for guidelines and continuing education focused on this issue to standardize practice, an intervention likely to improve quality of diagnoses and to reduce unnecessary costs

Spatio-temporal patterns in fin whale <i>Balaenoptera physalus</i> habitat use in the northern Gulf of St. Lawrence

Significant ecosystem changes in the Gulf of St. Lawrence (GSL), Canada, have had far-reaching effects at all trophic levels. The abundance of fin whales Balaenoptera physalus has declined significantly in the northern GSL over the past decade. This study aimed to test the hypothesis that the observed decline was correlated to changing environmental conditions. Cetacean sightings data from 292 surveys, resulting in 2986 fin whale encounters from 2007 to 2013, were used to fit 2 separate generalised additive models in terms of (1) bathymetric and oceanographic variables (the proxy model) and (2) modelled krill biomass (the prey model). The concept of ‘handling time’ was introduced to correct for time off search effort, applicable to other studies relying on opportunistically sampled data. While a positive correlation between krill biomass and fin whale numbers was found, the performance of the proxy model (24.2% deviance explained) was overall better than the prey model (11.8%). Annual predictive maps derived from the final proxy model highlighted 2 key areas with recurrently high relative fin whale abundance and a significant overlap with shipping lanes. While both models provided evidence for an annual decline in relative fin whale abundance, static bathymetric features were the most important predictors of habitat use, and no correlation between dynamic variables and the decline was found. High resolution prey data and a better understanding of the feeding ecology of fin whales are proposed to further investigate the predator-prey relationship and decline of fin whales in the GSL

Screening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathy

Background Advances in genetic technology have revealed that variation in the same gene can cause both rare familial and common sporadic forms of the same disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic intracerebral hemorrhage (ICH) in the elderly, can also occur in families in an autosomal dominant pattern. The majority of affected families harbor mutations in the Beta amyloid Peptide (Aβ) coding region of the gene for amyloid precursor protein (APP) or have duplications of chromosomal segments containing APP. Methodology/Principal Findings A total of 58 subjects with a diagnosis of probable or definite CAA according to validated criteria were included in the present study. We sequenced the Aβ coding region of APP in 58 individuals and performed multiplex ligation-dependent probe amplification to determine APP gene dosage in 60. No patient harbored a known or novel APP mutation or gene duplication. The frequency of mutations investigated in the present study is estimated to range from 0% to 8% in individuals with probable CAA in the general population, based on the ascertained sample size. Conclusions/Significance We found no evidence that variants at loci associated with familial CAA play a role in sporadic CAA. Based on our findings, these rare highly-penetrant mutations are unlikely to be seen in sporadic CAA patients. Therefore, our results do not support systematic genetic screening of CAA patients who lack a strong family history of hemorrhage or dementia.National Institute of Neurological Disorders and Stroke (U.S.) (grant K23NS042695)American Heart AssociationAmerican Stroke Association (Bugher Foundation for Stroke Prevention Research

Screening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathy

Background Advances in genetic technology have revealed that variation in the same gene can cause both rare familial and common sporadic forms of the same disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic intracerebral hemorrhage (ICH) in the elderly, can also occur in families in an autosomal dominant pattern. The majority of affected families harbor mutations in the Beta amyloid Peptide (Aβ) coding region of the gene for amyloid precursor protein (APP) or have duplications of chromosomal segments containing APP. Methodology/Principal Findings A total of 58 subjects with a diagnosis of probable or definite CAA according to validated criteria were included in the present study. We sequenced the Aβ coding region of APP in 58 individuals and performed multiplex ligation-dependent probe amplification to determine APP gene dosage in 60. No patient harbored a known or novel APP mutation or gene duplication. The frequency of mutations investigated in the present study is estimated to range from 0% to 8% in individuals with probable CAA in the general population, based on the ascertained sample size. Conclusions/Significance We found no evidence that variants at loci associated with familial CAA play a role in sporadic CAA. Based on our findings, these rare highly-penetrant mutations are unlikely to be seen in sporadic CAA patients. Therefore, our results do not support systematic genetic screening of CAA patients who lack a strong family history of hemorrhage or dementia.National Institute of Neurological Disorders and Stroke (U.S.) (grant K23NS042695)American Heart AssociationAmerican Stroke Association (Bugher Foundation for Stroke Prevention Research

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium.

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium

OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations

A Literature Review of Zika Virus

Zika virus is a mosquitoborne flavivirus that is the focus of an ongoing pandemic and public health emergency. Previously limited to sporadic cases in Africa and Asia, the emergence of Zika virus in Brazil in 2015 heralded rapid spread throughout the Americas. Although most Zika virus infections are characterized by subclinical or mild influenza-like illness, severe manifestations have been described, including Guillain-Barre syndrome in adults and microcephaly in babies born to infected mothers. Neither an effective treatment nor a vaccine is available for Zika virus; therefore, the public health response primarily focuses on preventing infection, particularly in pregnant women. Despite growing knowledge about this virus, questions remain regarding the virus’s vectors and reservoirs, pathogenesis, genetic diversity, and potential synergistic effects of co-infection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health intervention in the current Zika virus epidemic

Patterns in immunohistochemical usage in extended core prostate biopsies: comparisons among genitourinary pathologists and nongenitourinary pathologists

CONTEXT: Immunohistochemical (IHC) stains have known utility in prostate biopsies and are widely used to augment routine staining in difficult cases. Patterns in IHC utilization and differences based on pathologist training and experience is understudied in the peer-reviewed literature. OBJECTIVES: To compare the rates of IHC usage between specialized (genitourinary; [GU]) and nonspecialized (non-GU) pathologists in extended core prostate biopsies (ECPBs) and the effects of diagnosis; and in cancer cases Gleason grade, disease extent, and perineural invasion on the rate. DESIGN: Consecutive ECPBs from 2009-2011 were identified and billing data were used to determine the number of biopsies and IHC stains per case. Diagnoses were mapped and in cancer cases, Gleason grade, extent of disease, and perineural invasion were recorded. Pathologists were classified as GU or non-GU on the basis of training and experience. RESULTS: A total of 618 ECPBs were included in the study. Genitourinary pathologists ordered significantly fewer IHC tests per case and per biopsy than non-GU pathologists. The rate of ordering was most disparate for biopsies of cancerous and benign lesions. For biopsies of cancerous lesions, high-grade cancer, bilateral disease, and perineural invasion decreased the rate of ordering in both groups. In cancer cases, GU pathologists ordered significantly fewer stain tests for highest Gleason grade of 3 + 3 = 6, for patients with focal disease and for patients with multiple positive bilateral cores. The effect of the various predictors on IHC ordering rates was similar in both groups. CONCLUSIONS: Genitourinary pathologists ordered significantly fewer IHC stain tests than non-GU pathologists in ECPBs. Guidelines to define when IHC workup is necessary and not necessary may be helpful to guide workups

Spatio-temporal patterns in fin whale (<i>Balaenoptera physalus</i>) habitat use in the northern Gulf of St. Lawrence

Significant ecosystem changes in the Gulf of St. Lawrence (GSL) have had far-reaching effects at all trophic levels. The abundance of fin whales (Balaenoptera physalus) has declined significantly in the northern GSL over the past decade. This study aimed to test the hypothesis that the observed decline was correlated to changing environmental conditions. Cetacean sighting data from 292 surveys, resulting in 2986 fin whale encounters from 2007 to 2013, were used to fit two separate generalised additive models in terms of (1) bathymetric and oceanographic variables (the proxy model) and (2) modelled krill biomass (the prey model). The concept of “handling time” was introduced to correct for time off search effort, applicable to other studies relying on opportunistically sampled data. While a positive correlation between krill biomass and fin whale numbers was found, the performance of the proxy model (24.2 % deviance explained) was overall better than the prey model (11.8 %). Annual predictive maps derived from the final proxy model highlighted two key areas with recurrently high relative fin whale abundance and a significant overlap with shipping lanes. While both models provided evidence for an annual decline in relative fin whale abundance, static bathymetric features were the most important predictors of habitat use and no correlation between dynamic variables and the decline was found. High resolution prey data and a better understanding of the feeding ecology of fin whales are proposed to further investigate the predator-prey relationship and decline of fin whales in the GSL