Intestinal fibrosis and stenosis are common complications of Crohn’s disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase [CH25H] converts cholesterol to 25-hydroxycholesterol [25-HC], which modulates immune responses and oxidative stress. In human intestinal samples from CD patients, we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme, using the sodium dextran sulphate [DSS]-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.

OBJECTIVE To describe the state of glycemic control in non-critically ill diabetic patients admitted to the PR University Hospital, and the adherence to current standard of care guidelines for the treatment of diabetes. METHODS This was a retrospective study of patients admitted to a General Medicine ward with Diabetes Mellitus as a secondary diagnosis. Clinical data was analyzed for the first 5 days and the last 24 hours of admission. RESULTS One hundred and forty-seven (147) non-critically ill diabetic patients were evaluated. The rate of hyperglycemia and hypoglycemia was 56.7% and 2.8%, respectively. Nearly 60% of patients were hyperglycemic during the first 24 hrs of admission and 54.2% during the last 24 hrs. Mean last glucose value before discharge was 189.6 ± 73 mg/dL. Most patients were treated with subcutaneous insulin with basal insulin alone used as the most common regimen. The proportion of patients classified as uncontrolled receiving basal-bolus therapy increased from 54.3% on day 1 to 60.0% on day 5, with still 40.0% receiving only basal insulin. Most of the uncontrolled patients had their insulin dose increased (70.1%), however, a substantial portion had no change (23.7%) or even had a decrease (6.2%) in their insulin dose. CONCLUSIONS Even though there are areas of improvement in the management of hospitalized diabetic patients, it is still suboptimal, probably due to clinical inertia. A comprehensive educational diabetes management program, along with standardized insulin orders should be implemented to improve the care of these patients.

Background: Several medical conditions require chronic anticoagulation, but there are potential long-term complications, including intracranial hemorrhages. Pituitary apoplexy (PA), caused by infarction or bleeding into the pituitary gland, is a rare condition that commonly occurs in the setting of a pituitary adenoma. However, several reports have shown an increased risk of PA associated with anticoagulation therapy. Recent case reports have shown that even the newer oral anticoagulants may increase the risk of PA. Typically patients present with an acute headache, visual disturbances and pituitary hormonal deficiencies. Management is controversial and includes either a conservative medical treatment versus a more aggressive surgical approach. We present a case of a PA induced by Apixaban, an orally active factor Xa inhibitor. Clinical Case: This is the case of a 45 years-old male patient with prior medical history of hyperthyroidism treated with radioiodine ablation, systolic heart failure and atrial fibrillation, receiving Apixaban for stroke risk reduction. The patient presented initially to the ER after developing an acute, pulsatile frontal headache, associated with nausea and vomiting. He was treated for a suspected acute gastroenteritis and was discharged home. Two days later the patient returned to the ER, with persistent headaches unresponsive to oral analgesics. This time, the patient also complained of decreased energy, difficulty concentrating, and memory problems. He denied visual changes, galactorrhea, decreased libido or polyuria. Vital signs were unremarkable and there was no orthostatic hypotension. Physical examination showed a male in mild distress due to pain. There were no visual field defects on confrontation, no neurological deficits, and an intact mental status. Brain imaging showed hemorrhage within the pituitary gland with associated edema, compatible with PA. There was no obvious evidence of a pre-existing pituitary adenoma. Laboratory workup did not reveal any hormonal deficiencies. The patient was managed conservatively with close neurological follow up and empiric high dose dexamethasone. Headaches improved significantly after treatment and eventually resolved. After clinical improvement, the patient was discharged home on physiologic replacement of glucocorticoids with outpatient follow up and plans for re-evaluation of hormonal axis. Conclusion: Oral anticoagulants can increase the risk of PA, even in the absence of a pre-existing pituitary adenoma, as other case reports have shown. Management is controversial, and although there are agents for reversal of Apixaban effects (recombinant factor Xa), their use in PA has not been described. This case was managed conservatively with excellent results. Although we cannot exclude a pre-existing pituitary adenoma in this patient, this case shows that Apixaban increases the risk of PA.

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Intestinal fibrosis and stenosis are common complications of Crohn’s disease (CD), frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidized cholesterol derivatives, with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase (CH25H) converts cholesterol to 25-hydroxycholesterol (25-HC), which modulates immune responses and oxidative stress. In human intestinal samples from CD patients we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme using the sodium dextran sulfate (DSS)-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.