Introduction. Transgenic rats with inducible angiotensin II (Ang II)-dependent hypertension (strain name: TGR[Cyp1a1-Ren2]) were generated by inserting the mouse Ren2 renin gene, fused to the cytochrome P450 1a1 (Cyp1a1) promoter, into the genome of the rat. The present study was performed to characterise the changes in plasma and kidney tissue Ang II levels and in renal haemodynamic function in Cyp1a1-Ren2 rats following induction of either slowly developing or malignant hypertension in these transgenic rats. Materials and Methods. Arterial blood pressure (BP) and renal haemodynamics and excretory function were measured in pentobarbital sodium-anaesthetised Cyp1a1-Ren2 rats fed a normal diet containing either a low dose (0.15%, w/w for 14-15 days) or high dose (0.3%, w/w for 11-12 days) of the aryl hydrocarbon indole-3-carbinol (I3C) to induce slowly developing and malignant hypertension, respectively. In parallel experiments, arterial blood samples and kidneys were harvested for measurement of Ang II levels by radioimmunoassay. Results. Dietary I3C increased plasma renin activity (PRA), plasma Ang II levels, and arterial BP in a dose-dependent manner. Induction of different fixed levels of renin gene expression and PRA produced hypertensive phenotypes of varying severity with rats developing either mild or malignant forms of hypertensive disease. Administration of I3C, at a dose of 0.15% (w/w), induced a slowly developing form of hypertension whereas administration of a higher dose (0.3%) induced a more rapidly developing hypertension and the clinical manifestations of malignant hypertension including severe weight loss. Both hypertensive phenotypes were characterised by reduced renal plasma flow, increased filtration fraction, elevated PRA, and increased plasma and intrarenal Ang II levels. These I3C-induced changes in renal haemodynamics, PRA and kidney Ang II levels were more pronounced in Cyp1a1-Ren2 rats with malignant hypertension. Chronic administration of the AT 1 -receptor antagonist,

Ketoacidosis is a rare but serious side effect of SGLT2 inhibitors. It is being increasingly reported as these drugs are now commonly being prescribed in the primary care setting. Awareness that DKA can occur in the setting of relative euglycemia is critical to recognize this life-threatening complication of diabetes. More research is needed to better understand the underlying pathophysiology and precipitating factors leading to ketoacidosis in SGLT-2 inhibitor treated patients.

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INTRODUCTION: In the United States, colorectal cancer (CRC) is the second leading cause of death. Colonoscopy and fecal immunochemical test (FIT) are recommended as first tier tests for colorectal cancer screening. Cologuard is an attractive and effective modality of screening in patients apprehensive of undergoing a colonoscopy with a sensitivity and specificity of upto 90%. We performed a retrospective chart review to assess the outcomes of cologuard testing and subsequent colonoscopy results in an outpatient population. METHODS: A total of 550 patients underwent cologuard testing in our outpatient internal medicine practice. We performed a retrospective chart review to identify patient characteristics in patients with a positive cologuard test and correlate them with colonoscopy findings. Primary outcome was to identify colonoscopy findings in patients with a positive cologuard test. Secondary outcome was to identify patient characteristics in this patient population. RESULTS: 52 of these patients (9.45%) had a positive cologuard test. The average age of these patients was 68 years. 222 of these were males and 328 females. Most of them were non-hispanic or non-latino whites (39), with two hispanics, and one American Indian. Nine patients refused to report their ethnicity. All of these patients were referred to gastroenterology for a screening colonoscopy. Out of the 52 patients that were referred, 34 (65.38%) underwent a screening colonoscopy. Four patients were lost to follow-up, eight patients could not undergo a screening colonoscopy secondary to significant medical co-morbidities and six declined the colonoscopy. 29 (85.29%) patients had an abnormal colonoscopy with significant findings. Five patients had a normal colonoscopy with no remarkable findings. The total number of polyps found in these patients was 70, ranging from one polyp seen in nine patients to 12 polyps seen in one patient. The most common location for a polyp was the sigmoid colon followed by the transverse colon, with fewest polyps seen in the cecum. The most common histological diagnosis was hyperplastic, followed by sessile serrated and villous adenomas. CONCLUSION: We noted a high degree of correlation between a positive cologuard test and the presence of colonic polyps. Cologuard is an effective and convenient non-invasive screening modality in patients that do not wish to undergo a colonoscopy. Appropriate follow-up and referral to gastroenterology is essential for patients with a positive cologuard test.

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INTRODUCTION: Inflammatory bowel disease (IBD) has a variety of both intestinal and extraintestinal manifestations. Among the range of extraintestinal manifestations of IBD, venous thromboembolism (VTE) is a rare complication with high morbidity and mortality. VTE can present in patients with both active disease, which is more prevalent, or in well-controlled disease, which suggests a prothrombotic risk in patients with IBD. The case below is a classic presentation of VTE in IBD, and raises questions involving lifelong anticoagulation. CASE DESCRIPTION/METHODS: A 62 year old male with ulcerative colitis presented to the office with a 2-week history of constant, achy pain in his right leg associated with swelling and stiffness of his right lower extremity. A right lower extremity venous duplex ultrasound revealed extensive thrombosis from the popliteal vein up to the common femoral vein. Despite a discussion about possible sequelae of untreated VTE such as further clot extension, acute pulmonary embolism, and death, the patient opted for outpatient treatment with lifelong apixaban. His swelling improved, and although he has had prior IBD exacerbations with significant bleeding, since the patient has been on apixaban, he has not had any significant bleeding. DISCUSSION: Patients with IBD have a threefold higher risk of VTE than the general population. Research suggests that it may be due to a complex interplay between inflammation and coagulation. Treatment of acute VTE in IBD patients has not been clearly defined and currently is similar to most patients. Consequently, the duration of anticoagulation is not established, and it is imperative to establish specific guidelines due to the risk of recurrent VTE in IBD. Currently, there are no data on the role of primary VTE prophylaxis for IBD patients in the outpatient setting and no specific biomarkers to identify IBD patients at risk. Future research should assess the prothrombotic risk in IBD to assist clinicians in preventive measures. Additional studies are needed to address the use of screening tests such as ultrasound or biomarkers. In this case, the patient was placed on lifelong apixaban due to his underlying risk factor of ulcerative colitis and showed clinical improvement with no significant bleeding. This case helps highlight the concern for major bleeding in a patient who has had previous significant major bleeding episodes during IBD exacerbations. In conclusion, VTE is a significant complication that should not be overlooked in patients with IBD.

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