Racial differences in P2Y12 inhibitor responsiveness in patients undergoing neuro-endovascular procedures: A cohort from the Middle East.

BACKGROUND: Data on P2Y12 inhibitors responsiveness from the middle east is scarce. We sought to investigate patient responsiveness to P2Y12 inhibitors within a cohort of major races that characterize the UAE population. The secondary objective was to assess risk factors for hyper and hypo-responsiveness in this population. METHODS: We conducted a cross-sectional study on adults who received either clopidogrel or ticagrelor treatments and had platelet responsiveness testing before undergoing neuro-endovascular interventions at our quaternary care hospital between March 2015 and April 2019. RESULTS: During the study period, 249 subjects met the inclusion criteria. Overall, 17.3 % were hyper-responsive and 25.7 % were hypo-responsive to P2Y12 inhibitors. When comparing between the P2Y12 inhibitors, rates of hyper-responsiveness were significantly higher to ticagrelor when compared to clopidogrel (11 versus 6 %, p = 0.02 respectively). Contrarily, hypo-responsiveness rates were significantly higher in clopidogrel treated patients compared to their ticagrelor treated counterparts (23 versus 2 %, p < .001 respectively). Patients of Middle-Eastern origin showed a significantly higher rate of hypo-responsiveness to both clopidogrel and ticagrelor when compared to other races (41.1 % and 26.7 %, P < 0.001 respectively). Asians showed the highest rates of hyper-responsiveness for both agents. Multivariate logistic regression analysis showed that proton pump inhibitors and statin combination, (OR: 6.39, 95 %CI [1.60, 25.392]), and Middle East vs. Indian subcontinent patients (OR: 4.67, 95 %CI [1.79-12.14]) were independent predictors of hypo-responsiveness to both P2Y12 inhibitors. CONCLUSION: This study demonstrated a high rate of hypo-responsiveness to P2Y12 inhibitors in a UAE cohort of patients undergoing neuro-endovascular procedures. In addition, therapeutic responsiveness to P2Y12 inhibitors varied markedly based on the racial background. Future larger studies are needed to evaluate genetic variations that may contribute to this rate of hypo-responsiveness in our population.

Insights into Exosome Transport through the Blood-Brain Barrier and the Potential Therapeutical Applications in Brain Diseases.

Drug delivery to the central nervous system (CNS) is limited due to the presence of the blood-brain barrier (BBB), a selective physiological barrier located at the brain microvessels that regulates the flow of cells, molecules and ions between the blood and the brain. Exosomes are nanosized extracellular vesicles expressed by all cell types and that function as cargos, allowing for communication between the cells. The exosomes were shown to cross or regulate the BBB in healthy and disease conditions. However, the mechanistic pathways by which exosomes cross the BBB have not been fully elucidated yet. In this review, we explore the transport mechanisms of exosomes through the BBB. A large body of evidence suggests that exosome transport through the BBB occurs primarily through transcytosis. The transcytosis mechanisms are influenced by several regulators. Inflammation and metastasis also enhance exosome trafficking across the BBB. We also shed light on the therapeutical applications of exosomes for treating brain diseases. Further investigations are essential to provide clearer insights related to trafficking of exosomes across the BBB and disease treatment.

Is Cefoxitin a Carbapenem Sparing Agent in the Management of Urinary Tract Infections Caused by ESBL Producing Enterobacterales?

Background: Cefoxitin has shown in vitro activity against Extended-Spectrum ß-Lactamase (ESBL) producing Enterobacterales. Outcome data regarding cefoxitin as a carbapenem sparing agent in the management of urinary tract infections (UTI) are scarce. We sought to evaluate the clinical and microbiologic efficacy of cefoxitin as compared to ertapenem. Methods: A retrospective observational study was conducted at our quaternary care institution between May 2015 and March 2019. We identified all patients who received cefoxitin for the treatment of UTI during the study period and used Charlson Comorbidity Index to select a matching cohort from patients who received ertapenem. Primary end points were clinical and microbiological cure. Results: Thirty patients who received cefoxitin were matched with 55 patients who received ertapenem. Clinical cure was marginally in favor of ertapenem: 83.2% in cefoxitin group versus 96.8% in ertapenem group (P = .042). However, 90-day recurrence was in favor of cefoxitin: 13.5% in cefoxitin group versus 34.8% in ertapenem group (P = .045). Microbiologic cure was not significant between the 2 groups with 88.6% success in cefoxitin versus 100% in ertapenem. Additionally, the group difference on 30-day recurrence or relapse rates and the 90-day mortality rate were not clinically significant. Conclusion: Cefoxitin achieved similar microbiologic cure rate when compared to ertapenem for the treatment of UTI caused by ESBL-producing Enterobacterales. No significant differences were found in 30-day recurrence/relapse or mortality rates. Larger randomized controlled trials are required to identify the clinical sittings in which cefoxitin could be used as a carbapenem-sparing agent in the treatment of UTI.

Hypertriglyceridemia in Critically Ill Patients With SARS-CoV-2 Infection.

BACKGROUND: Patients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs. OBJECTIVE: We sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase. METHODS: A retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay. RESULTS: Of the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers. CONCLUSION AND RELEVANCE: The incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.

New findings: a very high natural radiation area in Afra hot springs, Jordan.

A high natural radiation zone was investigated for the first time in Afra hot springs of Jordan. The radiation levels were measured using a portable Geiger-Muller counter and an Na(Tl) detector. The measured absorbed dose rates in air ranged from 10 to 1800 nGy h(-1), suggesting that the concentration of natural radioactive materials is very high compared with their normal abundance in crustal rocks. A single high-radiation zone was also found in a nearby area where a gamma radiation dose rate of 4.0 mGy h(-1) was measured. On the basis of this measurement, the area was marked as a high-radiation zone. This region is far from tourist areas and not easily reached. No intervention measures are needed to protect people because the spa area is not well inhabited, having only daily visitors (average frequency of 10 days per year per individual). The dose received by workers in the spa area should be considered and the worker should be monitored by personal radiation dosimeters, such as thermoluminescent dosimeters.