Research Spotlight

Ashktorab, H., D. Delker, P. Kanth, A. Goel, J. M. Carethers and H. Brim (2019). “Molecular Characterization of sessile serrated adenoma/polyps from a large African American cohort.” Gastroenterology Apr 17. [Epub ahead of print].

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Colorectal cancer is the second leading cause of cancer-related deaths in the United States and rates are highest among African Americans (AAs). Sessile serrated adenoma/polyps (SSA/Ps) may be precursors of up to 30% of colorectal cancers. Flat and mucinous features make SSA/Ps difficult to detect and similarities to histological features of benign hyperplastic polyps (HPs) make them difficult to be accurately diagnosed. As such, there is a need for specific sensitive molecular biomarkers for accurate and reliable diagnosis. Our aim was to assess the diagnostic value of molecular biomarkers that may distinguish SSA/Ps from HPs among AA patients . . . The prevalence of SSA/Ps in our study was 2.5% (252/10,027 colonoscopies) which is higher than that published by other groups. Moreover, these lesions were primarily distal which could associate with a different molecular profile. Indeed, neither CIMP nor MSI appear to be potential markers for these distal SSA/Ps. In addition to location, age might also be a determining factor for CIMP and MSI status. Indeed, Lui et al. reported that SSA methylation increased dramatically with age and associated with dysplasia. Our SSA/Ps patients were generally young (mean 56 years) and displayed no dysplasia. This is possibly one of the reasons why CIMP was not a distinguishing criterion in our cohort. MSI, a by-product of CIMP when it affects MLH1, was also not a differentiating feature between SSA/Ps and HPs in our AA population. Nearly 60% of our SSA/P cases displayed BRAF V600E mutation which has been previously associated with hypermethylation. This is not the case in our study, perhaps because the CIMP marker panel we used was not specific for SSA/Ps, particularly distally located ones. In a genome-wide DNA methylation and gene expression study in SSA/Ps and conventional adenomas, Parker et al. established a test panel of six hypermethylated regions (LOX, LEF1-AS1, SFRP4, ZNF793, SYT9, and LINC00693) that distinguished pre-cancers from normal mucosa and SSA/Ps from conventional adenomas with high accuracy. The test panel we used in our study differed from the ones established in their study. MUC6 demonstrated the highest fold-difference suggesting that its high expression might correlate with SSA/P pathogenesis. Three other genes (SEMG1, TRNP1 and FSCN1) also showed significantly higher expression in AA SSA/Ps. Several studies have shown that among four mucin genes clustered on chromosome 11 (MUC2, MUC5AC, MUC5B and MUC6), MUC2 and MUC5B are highly subject to DNA methylation and histone modification, whereas MUC5AC is rarely influenced by epigenetic regulation and MUC6 does not undergo significant epigenetic regulation. Indeed, Parker et al. also demonstrated that SSA/Ps have high expression of MUC6 and SEMG1, among others. It is worth noting that MUC6 fold difference in SSA/Ps vs. HPs (37.2X) was much higher than that noted for SSA/Ps compared to uninvolved normal colon (12.9X). Therefore, these difficult-to-diagnose lesions could be evaluated for MUC6 and SEMG1 expression in addition to BRAF V600E to differentiate SSA/Ps from HPs. Among AA SSA/Ps, it remains to be seen if TRNP1 and FSCN1 elevated expression solely segregates with race. However, these factors individually, or collectively, may lead to better SSA/P detection and early diagnosis, particularly through non-invasive colorectal cancer screening approaches. (Excerpt from text, manuscript in process, p. 1, 3.)

Lai, J. C., R. S. Rahimi, E. C. Verna, M. R. Kappus, M. A. Dunn, M. McAdams-DeMarco, C. E. Haugen, M. L. Volk, A. Duarte-Rojo, D. R. Ganger, J. G. O’Leary, J. L. Dodge, D. Ladner and D. L. Segev (2019). “Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study.” Gastroenterology 156(6): 1675-1682.

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BACKGROUND & AIMS: Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated Liver Frailty Index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality. METHODS: Adults without hepatocellular carcinoma who were on the liver transplantation waitlist at 9 centers in the United States (N = 1044) were evaluated using the LFI; LFI scores of at least 4.5 indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate sub-hazard ratios (sHRs) of waitlist mortality (death or removal from the waitlist). RESULTS: Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio 1.56, 95% confidence interval [CI] 1.15-2.14) or HE (odd ratio 2.45, 95% CI 1.80-3.33) than for those without these features. Larger proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared with patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR 1.52, 95% CI 1.14-2.05), HE (sHR 1.84, 95% CI 1.38-2.45), and frailty (sHR 2.38, 95% CI 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR 1.82, 95% CI 1.31-2.52); ascites and HE were not. CONCLUSIONS: Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be used to objectively quantify risk of death related to frailty-in excess of liver disease severity-in patients with cirrhosis.

Mageto, Y. (2019). “The Increasing Use of Social Media for Medical Information: Should Healthcare Providers Be Concerned?” Ann Am Thorac Soc 16(5): 544-546.

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During the last decade, social media use among adults in the United States has increased exponentially. Intuitively, we might assume that the increase in use primarily involves Gen Xers (born 1965–1980) and younger generations. However, Traditionalists (born 1900–1945) and Baby Boomers (born 1946–1964) have also been noted to have a significant uptick in their use of social media. Usage has increased from 2% in 2005 to 25% in 2015. Many members of this generation have become increasingly savvy with their smartphones, using them to record conversations in physician’s offices as well as looking up information on the Internet. The most commonly used platforms are Facebook, Google, and YouTube. These same generations (Traditionalists and Baby Boomers) have increasingly turned to the Internet, accessing websites, viewing videos, and discussing their medical information online with other patients, caregivers, and anyone else who desires to chime in. YouTube and other web media platforms were never designed as a platform for medical research or medical education, but by default, they have become a platform for reporting/sharing research, medical education, and patient support. This invites the question: Why should we be concerned about what is posted on YouTube? If one simply views it as an entertainment platform, then it should not be an issue. But because it has become a platform for healthcare, it is past time to have additional discussions/research going forward, developing tools to assess content and use of said content, and holding those who post inaccurate and harmful information accountable. (Excerpt from text, p. 544; no abstract available.)

Snyder, R. J., J. Jensen, A. J. Applewhite, K. Couch, W. S. Joseph, J. C. Lantis Ii and T. E. Serena (2019). “A Standardized Approach to Evaluating Lower Extremity Chronic Wounds Using a Checklist.” Wounds 31(5 Suppl): S29-s44.

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As the population ages and more people live with diabetes, obesity, and vascular disease, chronic wounds have become more prevalent. Increasingly, wound care falls into the hands of clinicians who may be new to the specialty. To facilitate a better understanding of wounds and to ensure all integral items for best outcomes are considered, an interprofessional panel of wound care experts developed a checklist to aid in lower extremity wound identification, assessment, evaluation, and potential complication recognition. This checklist focuses on an evidence-based approach to obtaining a medical history, evaluating the wound, determining the etiology, and assessing perfusion, edema, infection, and neurologic status. The goal of this fundamental evaluation tool is to help the clinician move towards the next steps in optimizing patient care. Evidence-based support for each item on the checklist is reviewed and detailed for clinician reference.

Silfvast-Kaiser, A., R. Youssef and S. Y. Paek (2019). “Diet in hidradenitis suppurativa: a review of published and lay literature.” Int J Dermatol Apr 21. [Epub ahead of print].

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Hidradenitis suppurativa (HS) is a chronic, recurring, inflammatory skin disorder resulting in skin abscesses and sinus tracts of the skin folds. Hidradenitis suppurativa remains a disease with limited treatment options. Management of disease activity with dietary modification has been of considerable interest to the HS patient community. Limited evidence exists to support dietary changes for treatment of HS. Strategies such as eliminating dairy products, limiting simple carbohydrate and sugar intake, and avoiding nightshades (Solanaceae) and foods containing brewer’s yeast have been reported to be helpful in some patients. Several supplements have also been touted as beneficial. Herein, we review the existing dietary recommendations in both peer-reviewed and lay literature in an attempt to consolidate and evaluate existing information, while stimulating further inquiry into the role of diet in HS. Although dietary modifications are often of considerable interest to HS patients, there is a paucity of data regarding diet as it relates to HS. It is unclear whether diet may prove to be of value in limiting the severity of HS. Further research is needed to determine the potential benefits of these dietary changes.