Background: To compare the effect of different dosages of subconjunctival bevacizumab with its topical administration on preventing the development of corneal neovascularization (CNV) in a rat model of corneal chemical injury. Methods: Neovascularization was induced by pressing a 2-mm diameter alkaline-coated applicator on the central cornea of the right eye of 50 anesthetized male rats. Immediately after cauterization, rats were divided randomly into 5 groups. Groups 1–4 received a subconjunctival injection of 0.02 ml of normal saline (control) or 1, 5 and 25 mg/ml of bevacizumab, respectively. In the fifth group, topical bevacizumab was instilled daily for 7 consecutive days. After 7 days, digital photographs of the cornea were taken and the area of the neovascularized cornea was calculated. Results: Analysis of digital photographs showed that, compared with the controls, a single subconjunctival injection of at least 0.1 mg of bevacizumab (5 mg/ml) – immediately after corneal cauterization – effectively decreased CNV after 7 days. Injection of 25 mg/ml of bevacizumab in the fourth group increased the avascular area more than twofold, compared with the saline-treated group (32.2% compared with 15%, p < 0.001). This difference between groups 4 and 2 was statistically significant (p = 0.04). Although topical delivery of 25 mg/ml bevacizumab was effective to inhibit CNV (p = 0.004), the results were similar to those of the third group. Qualitative microscopic evaluation of the cornea was compatible with the gross findings, as bevacizumab-treated groups had less intense corneal vessel channels and inflammation. Conclusion: Both subconjunctival and topical bevacizumab can prevent CNV in rats.

Guidelines on valve replacement recommend aortic valve replacement for patients with severe aortic regurgitation (AR) with symptoms or left ventricular (LV) dysfunction. However, the optimal timing of surgery for asymptomatic AR patients without LV dilation or dysfunction is not known. There are data to suggest that excess volume load imposed by AR may not only produce subclinical LV dysfunction, but produce neurohormonal activation similar to the heart failure syndrome resulting in reduced survival. The study by Myerson et al. is the first to investigate the predictive ability of cardiac MRI (CMR) for the outcome of asymptomatic patients with AR. They studied 113 asymptomatic patients with moderate-to-severe AR on echocardiography in four centers. A total of 39 (35%) patients developed symptoms or an indication for surgery over a mean follow-up period of 2.6 years. AR volume, AR regurgitant fraction, LV end-diastolic and end-systolic volumes had high discriminatory powers (area under curve of 0.96, 0.93, 0.88 and 0.78, respectively) to predict these events. Higher association with the outcome was observed when LV end-diastolic volume and regurgitant fraction were combined. A significantly higher number of patients with regurgitant fraction >33% were likely to progress to surgery compared with patients with a regurgitant fraction of <33% (85 vs 8%; p < 0.001). These results demonstrate a potential role for CMR for risk stratification of patients with asymptomatic moderate or severe AR, given the ability of CMR to accurately quantify AR and LV volumes. Based on the data presented, it is possible that we may be waiting too long to offer surgery in patients with severe AR.

Background: Inpatient hypoglycemia has been shown to be associated with increased mortality, more complications, and greater length of stay [1]. Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are at greater risks for hypoglycemia due to their decreased degradation of insulin, reduced glycogen stores, and decreased renal gluconeogenesis. With the association between inpatient hypoglycemia and increased morbidity and mortality, it is valuable to determine other risks factors that may contribute to hypoglycemia in the hospital setting. Objective: Determine the rates of hypoglycemia (glucose &lt;70 mg/dl) and severe hypoglycemia (glucose &lt;54 mg/dl) along with risk factors, such as type of insulin used and initial hyperglycemia at admission, for patients with diabetes mellitus (DM) and CKD/ESRD. Methods: A retrospective cohort analysis was conducted on 74,266 hospitalized patients who had DM and CKD/ESRD or DM alone, within 155 HCA Healthcare hospitals from January 2019 through June 2019. Results: Among hospitalized patients with DM, hypoglycemia was more common in patients with ESRD (n=5234) compared to patients with CKD without ESRD (n=18659) and patients without CKD/ESRD (n=52373) (34.37% vs. 23.66% vs. 12.91%, respectively, p&lt;0.01). Similarly, severe hypoglycemia was more common in patients with ESRD compared to patients with CKD without ESRD, and patients without CKD/ESRD (18.09% vs. 11.19% vs. 5.28%, respectively, p&lt;0.01). When evaluating patients with ESRD, a higher point of care (POC) glucose at time of admission was associated with an increased risk of subsequent hypoglycemia. Within the first 24 hours of hospital admission, hypoglycemia was more common if the patient’s initial POC glucose was greater than 300 with an incidence of 13.67% compared to 11.21% (n=955, p=0.033). Among patients with ESRD and an admission glucose &gt; 300, having an order for dialysis within the first 24 hours of admission was associated with increased risk of hypoglycemia (OR= 1.2181, p=0.0014). Diabetics with subsequent hypoglycemia had higher initial glucose levels on admission when compared to diabetics who did not experience hypoglycemia during their hospital stay. Mean = 221.61±82.32 vs 205.54±74.51 (p=0.000002). Conclusion: In hospitalized patients with DM, CKD and ESRD are associated with increased risk of hypoglycemia. Amongst diabetics, patients with ESRD and CKD account for over 50% of cases of severe hypoglycemia. Severe hypoglycemia occurred in 18% of patients who had both diabetes and ESRD. An elevated glucose at admission is associated with a subsequent hypoglycemia in patients with ESRD. It is important to manage DM in patients with CKD and ESRD carefully as they may be more likely to experience hypoglycemia due to overcorrection and decreased clearance of insulin. 1.Hulkower et al., Diabetes Manag 2014 Mar;4(2):165–176.

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