Sex Differential in 15-Hydroxyprostaglandin Dehydrogenase Levels in the Lumen of Human Intracranial Aneurysms.

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs. METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, with 20 women and 18 men. Women and men were comparable on baseline characteristics. The mean plasma concentration of 15-PGDH did not differ statistically between sample A (62.8±16.2 ng/mL) and sample B (61.8±17.9 ng/mL; 95% confidence interval -6.6 to 9.4). The mean plasma concentration of 15-PGDH in IA lumens of samples A and B was significantly higher in men (73.8±13.5 ng/mL) than women (49.6±7.8 ng/mL; P\u3c0.0001). CONCLUSIONS: Higher enzyme levels of 15-PGDH exist in the lumen of IAs of men compared with women. This observation could explain why aspirin confers better protection against IA rupture in men than in women. The susceptibility of an individual to aspirin may differ according to the level of 15-PGDH

Cerebral Arteriovenous Malformations: Evaluation and Management.

There has been increased detection of incidental AVMs as result of the frequent use of advanced imaging techniques. The natural history of AVM is poorly understood and its management is controversial. This review provides an overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management of AVMs. The authors discussed the imaging techniques available for detecting AVMs with regard to the advantages and disadvantages of each imaging modality. Furthermore, this review paper discusses the factors that must be considered for the most appropriate management strategy (based on the current evidence in the literature) and the risks and benefits of each management option

Cerebrospinal Fluid Leakage and Cerebral Venous Sinus Thrombosis: A Case Report

Cerebrovascular venous thrombosis is an uncommon entity that may occur in the sinuses of the dura, the cortical veins, or the deep venous system. Common etiologies include states of hypercoagulability, such as oral contraceptives intake, malignancy, and trauma. Additional causes include inherent thrombophilic states, such as those caused by systemic lupus erythematosus, protein C or S deficiency, and antithrombin III deficiency. The pathogenesis of cerebral venous sinus thrombosis stems from the obstruction of venous outflow. Consequently, venous engorgement occurs, leading to decreased effective blood flow and white matter edema. Infarction or hemorrhage are not uncommon in the setting of venous thrombosis. Intracranial pressure also rises. The most common presenting symptom is headache.2,3 The impact of intracranial hypotension due to cerebrospinal fluid (CSF) leak on venous flow and thrombosis is not clear.1, 4-8, 10, 11 We present the case and treatment course of a patient who initially presented with an acute venous sinus thrombosis and in was later found to have a CSF leak and intracranial hypotension

Co-infection in patients with COVID-19 in Tripoli Northern Lebanon: germs involved and antibiotic sensitivity profile.

Introduction: A considerable proportion of patients hospitalized with coronavirus disease 2019 (COVID-19) acquired bacterial infections. The aim of this study was to investigate the etiology and antimicrobial resistance of bacterial co-infection for more informed antimicrobial treatment. Methods: This retrospective study reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Northern Lebanon, Nini Hospital between august 2020-september 2021. According to the inclusion and exclusion criteria, patients who acquired bacterial infection were enrolled. Demographic, etiology and antimicrobial resistance data of the co-infection were collected. Results: The rate of infection by Gram-negative bacteria was 61.7%, while the rate of infection by Gram-positive bacteria was 23.4%. Escherichia coli was the dominant species isolated in this study (25.5%), followed by Candida spp (14.9%). With regard to fungal infection, there were 14.9% cases of yeast infection. The respiratory infection was the majority (42.5%), followed by blood infection (32%) and urine infection (25.5%). The analysis of antibiotics sensitivity results showed us that 44.4% of isolated Enterobacteriaceae were resistant to carbapenem, 16.66% were secretors of ESBL. We noted that 27.77% of Enterobacteriaceae were XDR. All isolates of Staphylococcus aureus were resistant to the methicillin. Conclusion: Bacterial co-infection may occur in patients hospitalized with COVID-19 and lead to high mortality. Gram-negative bacteria, especially Escherichia coli, S. maltophilia, and P. aeruginosa were the main bacteria, and the resistance rates of the major isolated bacteria were generally high. Keywords: COVID-19, co-infection, antibioresistance, Lebanon

The Use of Prasugrel and Ticagrelor in Pipeline Flow Diversion

Background: Despite the routine clopidogrel/aspirin anti-platelet therapy, complications like thromboembolism, continue to be encountered with PED. We studied the safety and the efficacy of prasugrel in the management of clopidogrel non-responders treated for intracranial aneurysms. Methods: 437 consecutive neurosurgery patients were identified between January 2011 and May 2016. Patients allergic or having \u3c30% platelet-inhibition with a daily 75mg of clopidogrel were dispensed 10mg of prasugrel daily (n=20) or 90mg of ticagrelor twice daily (n=2). The average follow-up was 15.8 months (SD=12.4 months). Patient clinical well being was evaluated with the modified Rankin Scale (mRS) registered before the discharge and at each follow-up visit. To control confounding we used multivariable mixed-effects logistic regression and propensity score conditioning. Results: 26 of 437(5.9%) patients (mean of age 56.3 years; 62 women [14,2%]) presented with a sub-arachnoid hemorrhage. 1 patient was allergic to clopidogrel and prasugrel simultaneously. All the patients receiving prasugrel (n=22) had a mRS\u3c2 on their latest follow-up visit (mean=0.67; SD=1.15). In a multivariate analysis, clopidogrel did not affect the mRS on last follow-up, p=0.14. Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (odds ratio[OR], 0.17; 95%Confidence Interval [CI95%], 0.01-2.70; p=0.21) neither with an increased thromboembolic accident rate (OR, 0.46; CI95%, 0.12-1.67; p=0.36) nor with an increased hemorrhagic event rate (OR, 0.39; CI95%,0.91-1.64; p=0.20). None of the patients receiving prasugrel deceased or had a long-term recurrence nor a hemorrhagic event, only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. 3 patients on clopidogrel passed during the study: (2) from acute SAH and (1) from intra-parenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR, 2.18; CI95%,0.11-43.27; p=0.61). The same associations were present in propensity score adjusted models. Conclusion: In a cohort of patients treated with PED for their intracranial aneurysms, prasugrel (10mg/day) is a safe alternative to clopidogrel resistant, allergic or non-responders

Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation Leading to Cerebral Aneurysm Pathogenesis.

OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1β, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs. CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies

Assessing a 600-mg Loading Dose of Clopidogrel 24 Hours Prior to Pipeline Embolization Device Treatment

Background: Clopidogrel/aspirin antiplatelet therapy routinely is administered 7-10 days before pipeline aneurysm treatment. Our study assessed the safety and efficacy of a 600-mg loading dose of clopidogrel 24 hours before Pipeline Embolization Device (PED) treatment. Methods: In this retrospective cohort study, we included patients treated with PED from October 2010 to May 2016. A total of 39.7% (n = 158) of patients were dispensed a loading dose of 650 mg of aspirin plus at least 600 mg of clopidogrel 24 hours preceding PED deployment, compared to 60.3% (n = 240) of patients who received 81-325 mg of aspirin daily for 10 days with 75 mg of clopidogrel daily preprocedurally. The mean follow-up was 15.8 months (standard deviation [SD] 12.4 months). modified Rankin Scale (mRS) was registered before the discharge and at each follow-up visit. To control confounding, we used multivariable logistic regression and propensity score conditioning. Results: Of 398 patients, the proportion of female patients was ~16.5% (41/240) in both groups and shared the same mean of age ~56.46 years. ~12.2% (mean = 0.09; SD = 0.30) had a subarachnoid hemorrhage. 92% (mean = 0.29; SD = 0.70) from the pretreatment group and 85.7% (mean = 0.44; SD = 0.91) of the bolus group had a mRS ≤2. In multivariate analysis, bolus did not affect the mRS score, P = 0.24. Seven patients had a long-term recurrence, 2 (0.83%; mean = 0.01; SD = 0.10) of which from the pretreatment group. In a multivariable logistic regression, bolus was not associated with a long-term recurrence rate (odds ratio [OR] 1.91; 95% confidence interval [CI] 0.27-13.50; P = 0.52) or with thromboembolic accidents (OR 0.99; 95% CI 0.96-1.03; P = 0.83) nor with hemorrhagic events (OR 1.00; 95% CI 0.97-1.03; P = 0.99). Three patients died: one who received a bolus had an acute subarachnoid hemorrhage. The mean mortality rate was parallel in both groups ~0.25 (SD = 0.16). Bolus was not associated with mortality (OR 1.11; 95% CI 0.26-4.65; P = 0.89). The same associations were present in propensity score-adjusted models. Conclusions: In a cohort receiving PED, a 600-mg loading dose of clopidogrel should be safe and efficacious in those off the standard protocol or showing \u3c30% platelet inhibition before treatment

Comparison of Outcomes in Level I vs Level II Trauma Centers in Patients Undergoing Craniotomy or Craniectomy for Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) carries a devastatingly high rate of morbidity and mortality. OBJECTIVE: To assess whether patients undergoing craniotomy/craniectomy for severe TBI fare better at level I than level II trauma centers in a mature trauma system. METHODS: The data were extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients \u3e 18 yr with severe TBI (Glasgow Coma Scale [GCS] score less than 9) undergoing craniotomy or craniectomy in the state of Pennsylvania from January 1, 2002 through September 30, 2017. RESULTS: Of 3980 patients, 2568 (64.5%) were treated at level I trauma centers and 1412 (35.5%) at level II centers. Baseline characteristics were similar between the 2 groups except for significantly worse GCS scores at admission in level I centers (P = .002). The rate of in-hospital mortality was 37.6% in level I centers vs 40.4% in level II centers (P = .08). Mean Functional Independence Measure (FIM) scores at discharge were significantly higher in level I (10.9 ± 5.5) than level II centers (9.8 ± 5.3; P \u3c .005). In multivariate analysis, treatment at level II trauma centers was significantly associated with in-hospital mortality (odds ratio, 1.2; 95% confidence interval, 1.03-1.37; P = .01) and worse FIM scores (odds ratio, 1.4; 95% confidence interval, 1.1-1.7; P = .001). Mean hospital and ICU length of stay were significantly longer in level I centers (P \u3c .005). CONCLUSION: This study showed superior functional outcomes and lower mortality rates in patients undergoing a neurosurgical procedure for severe TBI in level I trauma centers