Increased Frequency of KRAS Mutations in African Americans Compared with Caucasians in Sporadic Colorectal Cancer.

OBJECTIVES: The basis for over-representation of colorectal cancer (CRC) in African-American (AA) populations compared with Caucasians are multifactorial and complex. Understanding the mechanisms for this racial disparity is critical for delivery of better care. Several studies have investigated sporadic CRC for differences in somatic mutations between AAs and Caucasians, but owing to small study sizes and conflicting results to date, no definitive conclusions have been reached. METHODS: Here, we present the first systematic literature review and meta-analysis investigating the mutational differences in sporadic CRC between AAs and Caucasians focused on frequent driver mutations (APC,TP53, KRAS,PI3CA, FBXW7,SMAD4, and BRAF). Publication inclusion criteria comprised sporadic CRC, human subjects, English language, information on ethnicity (AA, Caucasian, or both), total subject number >20, and information on mutation frequencies. RESULTS: We identified 6,234 publications. Meta-analysis for APC, TP54, FBXW7, or SMAD4 was not possible owing to paucity of data. KRAS mutations were statistically less frequent in non-Hispanic Whites when compared with AAs (odds ratio, 0.640; 95% confidence interval (CI): 0.5342-0.7666; P=0.0001), while the mutational differences observed in BRAF and PI3CA did not reach statistical significance. CONCLUSIONS: Here, we report the mutational patterns for KRAS, BRAF, and PI3CA in sporadic CRC of AAs and Caucasians in a systematic meta-analysis of previously published data. We identified an increase in KRAS mutations in sporadic CRC in AAs, which may contribute to worse prognosis and increased mortality of CRC in AAs. Future studies investigating health-care disparities in CRC in AAs should control for KRAS mutational frequency.

Multiorgan Failure Predicts Mortality in Emphysematous Pancreatitis: A Case Report and Systematic Analysis of the Literature.

Emphysematous pancreatitis (EP) is a subtype of acute necrotizing pancreatitis (ANP) characterized by the presence of gas in and around the pancreas. Although investigators have studied prognostic factors in ANP, less is known about EP. We aimed to determine predictors of mortality and identify changes in management strategies for EP. A PubMed search was performed to identify EP cases. Data were gathered about patient demographics, clinical findings, laboratory results, radiological studies, procedures, outcomes, and mortality. Data were analyzed using univariate and multivariate logistic regression analyses. Including a case from our institution, the study cohort included 64 subjects. The overall mortality rate was 32.8% (21/64). On univariate analysis, age (P = 0.019), hypotension (P = 0.007), gas outside the pancreas on computed tomography imaging (P = 0.003), initial surgical evacuation (P = 0.007), and the development of multiorgan failure (P = 0.008) were associated with mortality. On multivariate analysis, only the development of multiorgan failure was found to be an independent predictor of mortality (P = 0.039). The overall mortality rate of 32.8% for EP is similar to the mortality rates published for ANP. The development of multiorgan failure in EP is strongly associated with increased mortality. Percutaneous and endoscopic approaches have been replacing surgical interventions.

The predictors of mortality and secular changes in management strategies in emphysematous gastritis.

BACKGROUND AND AIMS: Emphysematous gastritis (EG) is caused by invasion of the gastric wall by gas-producing organisms and carries mortality rate up to 60%. Our investigation aimed to determine the predictors of survival and the secular trends in survival rates of subjects with EG. METHODS: PubMed search was completed to identify previous cases of EG. In addition, we included a recent case from our center. Statistical analysis was completed with two-sided Chi2 tests for categorical data and t-tests for continuous variables using SPSS v. 22.0 (SPSS Inc, Chicago, IL). RESULTS: Study cohort included 59 adults. Mean age was 55.5 years; mean LOS was 28.6 days, and 44.1% of subjects were female. Subjects who had EG before 2000 had significantly higher rates of exploratory laparotomy compared to subjects who had EG after 2000 (62.5% vs. 22.2%, P=0.002). In contrast, subjects with EG after 2000 had significantly higher rates of EGD (55.6% vs. 18.8%, P=0.003) and lower rates of mortality (33.3% vs. 59.4%, P=0.046) compared to subjects with EG on or before 2000. In multivariate logistic regression analysis, the only independent predictor of mortality was length of stay (P=0.047). CONCLUSION: We showed that previously reported 60% mortality rate of EG has been reduced to 33.3% for cases reported after 2000. EGD has been utilized more often while surgical interventions are used only in carefully selected cases. Our data suggests that early endoscopic evaluation and optimal medical management can perhaps continue to improve survival in subjects with EG.

Celiac Disease Presenting as Profound Diarrhea and Weight Loss - A Celiac Crisis.

BACKGROUND Celiac disease is a hypersensitivity enteropathy that can have various presentations in adults. Rarely, patients can present with severe lab abnormalities, dehydration and weight loss caused by celiac disease - a celiac crisis. CASE REPORT A 46-year-old male with a past medical history significant for diabetes mellitus, type 2 (DM2) and recently treated Bell's Palsy presented to the emergency room complaining of weakness, diarrhea and lightheadedness. On presentation, the patient had a systolic blood pressure (SBP) of 60 mm Hg and a lactic acidosis with pH of 7.28. Infectious etiologies of diarrhea were ruled out. The patient had an EGD which showed erythema of the duodenal bulb. Serum anti-gliadin and anti-TTG IgA were both elevated suggesting Celiac disease. Biopsies showed histopathology consistent with celiac disease. The patient's diarrhea resolved after initiation of a gluten free diet. He gained 25 kilograms after discharge and did not require further hospitalizations for diarrhea. CONCLUSIONS Celiac crisis is a very rare presentation of celiac disease in adults but nonetheless should be considered in patients with marked metabolic derangements in the setting of osmotic diarrhea. Treatment consists of a gluten free diet and may require management with steroids and total parenteral nutrition (TPN).

Coactivator MED1 ablation in keratinocytes results in hair-cycling defects and epidermal alterations.

The transcriptional coactivator complex Mediator (MED) facilitates transcription of nuclear hormone receptors and other transcription factors. We have previously isolated the MED complex from primary keratinocytes (KCs) as the vitamin D receptor-interacting protein complex. We identified a role for MED in KC proliferation and differentiation in cultured KCs. Here, we investigated the in vivo role of MED by generating a conditional null mice model in which a critical subunit of the MED complex, MED1, is deleted from their KCs. The MED1 ablation resulted in aberrant hair differentiation and cycling, leading to hair loss. During the first hair follicle (HF) cycle, MED1 deletion resulted in a rapid regression of the HFs. Hair differentiation was reduced, and ß-catenin/vitamin D receptor (VDR)-regulated gene expression was markedly decreased. In the subsequent adult hair cycle, MED1 ablation activated the initiation of HF cycling. Shh signaling was increased, but terminal differentiation was not sufficient. Deletion of MED1 also caused hyperproliferation of interfollicular epidermal KCs, and increased the expression of epidermal differentiation markers. These results indicate that MED1 has a critical role in regulating hair/epidermal proliferation and differentiation.