Stratifying Intraductal Papillary Mucinous Neoplasms by Cyst Fluid Analysis: Present and Future

A significant proportion of patients with intraductal papillary mucinous neoplasms (IPMNs) undergo surgical resection in order to prevent or treat pancreatic cancer at the risk of significant perioperative morbidity. Efforts have been made to stratify the potential risk of malignancy based on the clinical and radiographic features of IPMN to delineate which cysts warrant resection versus observation. An analysis of the cyst fluid obtained by preoperative endoscopic examination appears to be correlative of cyst type and risk, whereas serum markers and radiographic findings have not yet reached a level of sensitivity or specificity that proves they are clinically meaningful. In this review, we investigate the current cyst fluid analysis studies and present those that have shown promise in effectively stratifying high-risk versus low-risk lesions. While new cyst fluid markers continue to be identified, additional efforts in testing panels and marker composites in conjunction with clinical algorithms have also shown promise in distinguishing dysplasia and the risk of malignancy. These should be tested prospectively in order to determine their role in guiding the surveillance of low-risk lesions and to evaluate the new markers detected by proteomics and genetic sequencing

Association of race and health insurance in treatment disparities of colon cancer: A retrospective analysis utilizing a national population database in the United States

Background Both health insurance status and race independently impact colon cancer (CC) care delivery and outcomes. The relative importance of these factors in explaining racial and insurance disparities is less clear, however. This study aimed to determine the association and interaction of race and insurance with CC treatment disparities. Study setting Retrospective cohort review of a prospective hospital-based database. Methods and findings In this cross-sectional study, patients diagnosed with stage I to III CC in the United States were identified from the National Cancer Database (NCDB; 2006 to 2016). Multivariable regression with generalized estimating equations (GEEs) were performed to evaluate the association of insurance and race/ethnicity with odds of receipt of surgery (stage I to III) and adjuvant chemotherapy (stage III), with an additional 2-way interaction term to evaluate for effect modification. Confounders included sex, age, median income, rurality, comorbidity, and nodes and margin status for the model for chemotherapy. Of 353,998 patients included, 73.8% (n = 261,349) were non-Hispanic White (NHW) and 11.7% (n = 41,511) were non-Hispanic Black (NHB). NHB patients were less likely to undergo resection [odds ratio (OR) 0.66, 95% confidence interval [CI] 0.61 to 0.72, p < 0.001] or to receive adjuvant chemotherapy [OR 0.83, 95% CI 0.78 to 0.87, p < 0.001] compared to NHW patients. NHB patients with private or Medicare insurance were less likely to undergo resection [OR 0.76, 95% CI 0.63 to 0.91, p = 0.004 (private insurance); OR 0.59, 95% CI 0.53 to 0.66, p < 0.001 (Medicare)] and to receive adjuvant chemotherapy [0.77, 95% CI 0.68 to 0.87, p < 0.001 (private insurance); OR 0.86, 95% CI 0.80 to 0.91, p < 0.001 (Medicare)] compared to similarly insured NHW patients. Although Hispanic patients with private and Medicare insurance were also less likely to undergo surgical resection, this was not the case with adjuvant chemotherapy. This study is mainly limited by the retrospective nature and by the variables provided in the dataset; granular details such as continuity or disruption of insurance coverage or specific chemotherapy agents or dosing cannot be assessed within NCDB. Conclusions This study suggests that racial disparities in receipt of treatment for CC persist even among patients with similar health insurance coverage and that different disparities exist for different racial/ethnic groups. Changes in health policy must therefore recognize that provision of insurance alone may not eliminate cancer treatment racial disparities.ECU ALS PLOS Institutional Account Progra

Towards a quantum theory of de Sitter space

We describe progress towards constructing a quantum theory of de Sitter space in four dimensions. In particular we indicate how both particle states and Schwarzschild de Sitter black holes can arise as excitations in a theory of a finite number of fermionic oscillators. The results about particle states depend on a conjecture about algebras of Grassmann variables, which we state, but do not prove.Comment: JHEP3 LaTex - 19 page

Differences in receipt of multimodality therapy by race,insurance status, and socioeconomic disadvantage in patientswith resected pancreatic cancer

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Background and Methods:Racial and socioeconomic disparities in receipt ofadjuvant chemotherapy affect patients with pancreatic cancer. However, differencesin receipt of neoadjuvant chemotherapy among patients undergoing resection arenot well�understood. A retrospective cross�sectional cohort of patients withresected AJCC Stage I/II pancreatic ductal adenocarcinoma was identified fromthe National Cancer Database (2014–2017). Outcomes included receipt ofneoadjuvant versus adjuvant chemotherapy, or receipt of either, defined asmultimodality therapy and were assessed by univariate and multivariate analysis.Results:Of 19 588 patients, 5098 (26%) received neoadjuvant chemotherapy, 9624(49.1%) received adjuvant chemotherapy only, and 4757 (24.3%) received nochemotherapy. On multivariable analysis, Black patients had lower odds ofneoadjuvant chemotherapy compared to White patients (OR: 0.80, 95% CI:0.67–0.97) but no differences in receipt of multimodality therapy (OR: 0.89, 95%CI: 0.77–1.03). Patients with Medicaid or no insurance, low educational attainment,or low median income had significantly lower odds of receiving neoadjuvantchemotherapy or multimodality therapy.Conclusions:Racial and socioeconomic disparities persist in receipt of neoadjuvantand multimodality therapy in patients with resected pancreatic adenocarcinoma.Discussion:Policy and interventional implementations are needed to bridge thecontinued socioeconomic and racial disparity gap in pancreatic cancer care.ECU/Wiley Open Access Publishing Agreemen

Perception Is Reality: quality metrics in pancreas surgery – a Central Pancreas Consortium (CPC) analysis of 1399 patients

Several groups have defined pancreatic surgery quality metrics that identify centers delivering quality care. Although these metrics are perceived to be associated with good outcomes, their relationship with actual outcomes has not been established

The diagnosis of pancreatic mucinous cystic neoplasm and associated adenocarcinoma in males: An eight‐institution study of 349 patients over 15 years

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137278/1/jso24582_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137278/2/jso24582.pd

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study

Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN

Interprofessional Collaboration Led by Health Professional Students: A Case Study of the Inter Health Professional Alliance at Virginia Commonwealth University

Background: Internationally recognized health experts have identified the need for an interdisciplinary approach to meet the healthcare needs of the 21st century, but academic institutions have been slow to take action. In response, eight health professional students at Virginia Commonwealth University developed a student-led organization, the Inter Health Professionals Alliance (IHPA), to foster a collaborative, interdisciplinary environment among health professional students.Methods and Findings: The eight students utilized a participatory action research approach to identify 1) an understanding behind the motivation for developing IHPA and 2) the core benefits of group involvement. Four benefits were identified: the development of knowledge and skills, interprofessional networks, professional competence, and role clarity. The case study demonstrated that students can engage in interdisciplinary collaboration from a student-initiated approach and likely improve the care of future patients. Drawing on personal experiences, IHPA board members outline five pieces of wisdom to aid fellow students in the development of student-led interdisciplinary organizations.Conclusions: With enthusiasm and support, students can transform their educational experiences to meet the healthcare needs of the twenty-first century

\u3cem\u3eABCC9\u3c/em\u3e Gene Polymorphism Is Associated with Hippocampal Sclerosis of Aging Pathology

Hippocampal sclerosis of aging (HS-Aging) is a high-morbidity brain disease in the elderly but risk factors are largely unknown. We report the first genome-wide association study (GWAS) with HS-Aging pathology as an endophenotype. In collaboration with the Alzheimer\u27s Disease Genetics Consortium, data were analyzed from large autopsy cohorts: (#1) National Alzheimer\u27s Coordinating Center (NACC); (#2) Rush University Religious Orders Study and Memory and Aging Project; (#3) Group Health Research Institute Adult Changes in Thought study; (#4) University of California at Irvine 90+ Study; and (#5) University of Kentucky Alzheimer\u27s Disease Center. Altogether, 363 HS-Aging cases and 2,303 controls, all pathologically confirmed, provided statistical power to test for risk alleles with large effect size. A two-tier study design included GWAS from cohorts #1-3 (Stage I) to identify promising SNP candidates, followed by focused evaluation of particular SNPs in cohorts #4-5 (Stage II). Polymorphism in the ATP-binding cassette, sub-family C member 9 (ABCC9) gene, also known as sulfonylurea receptor 2, was associated with HS-Aging pathology. In the meta-analyzed Stage I GWAS, ABCC9 polymorphisms yielded the lowest p values, and factoring in the Stage II results, the meta-analyzed risk SNP (rs704178:G) attained genome-wide statistical significance (p = 1.4 × 10-9), with odds ratio (OR) of 2.13 (recessive mode of inheritance). For SNPs previously linked to hippocampal sclerosis, meta-analyses of Stage I results show OR = 1.16 for rs5848 (GRN) and OR = 1.22 rs1990622 (TMEM106B), with the risk alleles as previously described. Sulfonylureas, a widely prescribed drug class used to treat diabetes, also modify human ABCC9 protein function. A subsample of patients from the NACC database (n = 624) were identified who were older than age 85 at death with known drug history. Controlling for important confounders such as diabetes itself, exposure to a sulfonylurea drug was associated with risk for HS-Aging pathology (p = 0.03). Thus, we describe a novel and targetable dementia risk factor

Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population

<p>Abstract</p> <p>Background</p> <p>Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (<it>CYP) 2C8</it>, <it>CYP2C9</it>, and <it>CYP2C19 </it>variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies.</p> <p>Methods</p> <p>RFLP assays were used to genotype <it>CYP2C8 </it>(<it>*2</it>, <it>*3</it>, <it>*4</it>) variant alleles in 204 unrelated Ghanaians. <it>CYP2C9*2 </it>and <it>CYP2C19 </it>(<it>*2 </it>and <it>*3</it>) variants were determined by single-tube tetra-primer assays while <it>CYP2C9 </it>(<it>*3, *4, *5 </it>and <it>*11</it>) variants were assessed by direct sequencing.</p> <p>Results</p> <p>Allelic frequencies were obtained for <it>CYP2C8*2 </it>(17%), <it>CYP2C8*3 </it>(0%), <it>CYP2C8*4 </it>(0%), <it>CYP2C9*2 </it>(0%), <it>CYP2C9*3 </it>(0%), <it>CYP2C9*4 </it>(0%), <it>CYP2C9</it>*5 (0%), <it>CYP2C9*11 </it>(2%), <it>CYP2C19*2 </it>(6%) and <it>CYP2C19*3 </it>(0%).</p> <p>Conclusion</p> <p>Allele frequency distributions for <it>CYP2C8</it>, <it>CYP2C9 </it>and <it>CYP2C19 </it>among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for <it>CYP2C9 </it>and <it>CYP2C19 </it>are reported for the first time among indigenous Ghanaian population.</p