Impact of Admission Hypertension on Rates of Acute Kidney Injury in Intracerebral Hemorrhage Treated with Intensive Blood Pressure Control.

BACKGROUND: Current guidelines recommend that rapid systolic blood pressure (SBP) lowering to 140 mmHg may be considered in intracerebral hemorrhage (ICH) patients regardless of initial SBP. However, limited safety data exist in patients presenting with varying degrees of severe hypertension. The purpose of this study was to determine whether there was an increased risk of acute kidney injury (AKI) based upon degree of presentation hypertension in ICH patients whose blood pressure was reduced intensively. METHODS: This retrospective, cohort study evaluated ICH patients treated with intensive blood pressure control (SBP ≤140 mmHg) who presented with three degrees of presentation hypertension: mild (SBP 141-179 mmHg), moderate (SBP 180-219 mmHg), and severe (SBP ≥ 220 mmHg). Univariate analysis of demographics variables, ICH severity, and factors known to impact AKI was conducted between the three groups. Post hoc testing was used to compare differences between specific groups, with a Bonferroni correction adjusting for multiple comparisons. Additionally, we conducted logistic regression analysis to determine whether baseline SBP group independently predicted AKI. RESULTS: We included 401 patients (177 with mild, 124 with moderate, and 100 with severe hypertension). There was a significant increase in the prevalence of AKI between groups, with the severe group experiencing the highest rate (p < 0.001). The presence of severe hypertension was also found to independently predict AKI development (odds ratio 2.6; p < 0.001). CONCLUSION: Our study observed higher rates of AKI in patients presenting with severe hypertension. Further research is needed to determine the most appropriate strategies for managing blood pressure in ICH patients presenting with higher SBP.

Novel GlyT1 inhibitor chemotypes by scaffold hopping. Part 2: development of a [3.3.0]-based series and other piperidine bioisosteres.

This Letter describes the development and SAR of a novel series of GlyT1 inhibitors derived from a scaffold hopping approach, in lieu of an HTS campaign, which provided intellectual property position. Members within this new [3.3.0]-based series displayed excellent GlyT1 potency, selectivity, free fraction, and modest CNS penetration. Moreover, enantioselective GlyT1 inhibition was observed, within this novel series and a number of other piperidine bioisosteric cores.

Reduction in Hypercalcemia Following Readjustment of Target Serum 25-Hydroxy Vitamin D Concentration during Cholecalciferol Therapy in Vitamin D-Deficient Critically Ill Patients.

The intent of this study was an evaluation of our effort to reduce the incidence of hypercalcemia in critically ill vitamin D-deficient patients with multiple traumatic injuries given cholecalciferol. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D concentration (25-OH vit D) of <20 ng/mL. Adult patients (>17 years of age) were given 10,000 IU of cholecalciferol daily with an intended target 25-OH vit D of >19.9 ng/mL. These patients were compared to a historical control group that underwent therapy with a higher target of >29.9 ng/mL. Patients received cholecalciferol via the feeding tube along with enteral nutrition (EN) until the target 25-OH vit D was achieved, EN discontinued, the nutrition support service signed off the patient, or the patient was discharged from the TICU. Patients were included if two consecutive weekly 25-OH vit D were measured. One hundred and three critically ill trauma patients were retrospectively studied. Fifty were given cholecalciferol therapy with the new lower target 25-OH vit D, and 53 were from a historical cohort aiming for the higher target. Hypercalcemia (serum ionized calcium concentration > 1.32 mmol/L) was reduced from 40% (21 out of 53 patients) to 4% (2 out of 50 patients; p < 0.001). None of the hypercalcemic patients were symptomatic. Readjustment of target 25-OH vit D concentration resulted in a ten-fold decrease in the rate of hypercalcemia and improved the safety of cholecalciferol therapy for critically ill patients with traumatic injuries.

Evaluation of the timing of MRSA PCR nasal screening: How long can a negative assay be used to rule out MRSA-positive respiratory cultures?

PURPOSE: Previous studies indicate that the polymerase chain reaction (PCR) nasal assay for methicillin-resistant Staphylococcus aureus (MRSA) has a consistently high (>95%) negative predictive value (NPV) in ruling out MRSA pneumonia; however, optimal timing of PCR assay specimen and respiratory culture collection is unclear. METHODS: A study including 736 patients from a community hospital system was conducted. Patients were included if they had undergone MRSA nasal screening with a PCR assay and had documented positive respiratory culture results. RESULTS: In the full cohort, the MRSA PCR nasal screen assay was demonstrated to have an NPV of 94.9% (95% confidence interval [CI], 92.8%-96.5%) in ruling out MRSA-positive respiratory cultures. When evaluating the NPV by level of care (ie, where the MRSA PCR nasal assay sample was collected), no significant difference between values for samples collected in an intensive care unit vs medical/surgical units was identified (NPV [95%CI], 94.9% [92.7%-96.6%] vs 95.3% [88.4%-98.7%]). Additionally, NPV remained high with use of both invasive (NPV [95%CI], 96.8% [92.7%-99.0%]) and noninvasive (NPV [95%CI], 94.5% [91.7%-96.2%]) respiratory sampling methods. Finally, when evaluating the effect of time between MRSA PCR nasal screening and respiratory sample collection, we found high NPVs for all evaluated timeframes: within 24 hours, 93.8% (90.1%-96.4%); within 25 to 48 hours, 98.6% (92.7%-100.0%); within 49 hours to 7 days, 95.7% (91.4%-98.3%); within 8 to 14 days, 92.9% (85.1%-97.3%); and after more than 14 days, 95.5% (84.5%-99.4%). CONCLUSION: We report high NPVs for up to 2 weeks between specimen collections, which allows clinicians to use a negative MRSA PCR nasal screen assay to rule out MRSA pneumonia, potentially leading to decreased exposure to MRSA-active antibiotics.