Association between high sensitivity C-reactive protein (hs-CRP) levels and the risk of major adverse cardiovascular events (MACE) and/or microembolic signals after carotid angioplasty and stenting

Background: To evaluate the association between pre/post-procedural high sensitive C-reactive protein (hs-CRP) level and hs-CRP difference, and the risk of major adverse cardiovascular events (MACE) or new diffusion-weighted MRI lesions after carotid angioplasty and stenting (CAS). Methods: In this study, conducted in 2016 in Shiraz (Iran), patients who underwent diagnostic angiography and CAS were recruited. CAS was performed with distal embolic protection device on patients with both standard and high risk of endarterectomy. Pre/post-procedural hs-CRP, and hs-CRP difference were determined by immunoenzymometric assay method. Results: A total of 50 patients with diagnostic angiography and 60 patients with CAS were enrolled. No death, myocardial infarction, ischemic or hemorrhagic stroke, and need to revascularization occurred during the 30-days of the post-procedural period. Accordingly, the statistical evaluation in associating MACE and hs-CRP levels was impossible. Angioplasty was associated with higher frequency of elevated post-procedural hs-CRP in comparison to angiography (P=0.003). The higher age, symptomatic lesions, negative history of hypertension, and hs-CRP difference had significant association with the presence of new DWI lesions in univariate analysis (all P<0.05). Angioplasty of left carotid bulb and post-procedural hs-CRP levels was very close to the level of significance (P=0.06). But only left sided lesions had positive association (P=0.037) and hypertension had negative association (P=0.037) in multivariate regression analysis. There were significant association between post-procedural hs-CRP level (P=0.02) and hs-CRP difference (P=0.003), and the number of new lesions; and the hs-CRP difference and the accumulated lesion surface area (P=0.009). Conclusion: Post-procedural hs-CRP and hs-CRP difference may predict embolic complications of CAS

Drug utilization evaluation of Rivaroxaban in both inpatient and outpatient settings: Using standard guidelines

Stroke-related atrial fibrillation (AF), deep vein thrombosis (DVT), and pulmonary thromboembolism (PE) are among the most common thromboembolic events. recently, direct oral anticoagulants (DOACs) have been slowly replacing warfarin. Rivaroxaban is a DOAC frequently prescribes to control thrombotic events. The safety and efficacy of Rivaroxaban are dependent on appropriate prescription, dosage, and other factors. This study is aimed to evaluate the Rivaroxaban utilization based on the standard protocol in both inpatient and outpatient settings. This cross-sectional/observational study was conducted for six months from 1st August 2018 to 1st February 2019 at a private hospital and also an outpatient clinic in Shiraz, Iran. First, a clinical pharmacist defined a standard protocol for Rivaroxaban utilization and several indexes (9 indexes for Non-valvular AF (NVAF) patients and 10 indexes for DVT/PE patients). Second, participants were classified into three groups (NVAF inpatients, NVAF outpatients, and DVT/PE patients). Finally, the adherence of Rivaroxaban utilization indexes in each group to was evaluated accordingly. Two hundred and forty one eligible patients were recruited into this study. Most patients (N=208), were NVAF. Rivaroxaban utilization was appropriate in 71.9%, 65.8%, and 50.6% of patients within groups 1, 2, and 3, respectively. Although medication interaction, administration regarding time/meal, and dose adjustment based on renal function showed the lowest compliance, the monitoring laboratory data and considering the underlying disorders were completely matched with the protocol. This study showed some critical errors in both settings, especially in DVT/PE patients (49.4% no match). Hence, the most productive collaboration must be developed between clinical pharmacists and clinical practitioners

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study

Objectives: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). Materials and methods: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. Results: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients \u3e 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P\u3c0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. Conclusion: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended

Combination of mesenchymal stem cells and nicorandil: an emerging therapeutic challenge against COVID-19 infection-induced multiple organ dysfunction.

The recent COronaVIrus Disease (COVID)-19 pandemic has placed an unprecedented burden on the drugs development opportunity to prevent the onset of multi-organ failure. Emerging experimental reports have highlighted beneficial effects of mesenchymal stem cells (MSCs) administration against COVID-19. MSCs and their derived exosomes may attenuate SARS-CoV-2 induced inflammatory response through managing the immune cells function and cytokine expression. Although these are promising results, the exposure of MSCs to chemical compounds with pharmacological activities may further improve their homing, survival and paracrine machinery. Nicorandil (N-[2-hydroxyethyl]-nicotinamide nitrate), an established adenosine triphosphate-sensitive potassium channel opener, is recently hypothesized to modulate inflammation as well as cell injury and death in COVID-19-affected lungs through inhibiting reactive oxygen species levels and apoptosis. Since it also exerts protective effects against hypoxia-induced MSC apoptosis, we assumed that transplanted MSCs combined to long-term nicorandil administration may survive longer in a severely inflamed microenvironment and have more beneficial effects in treatment of SARS-Cov-2 infection than MSCs alone

Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia

Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression

Mitochondrial neurogastrointestinal encephalomyopathy

Mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase gene leads to mitochondrial genomic dysfunction. Herein, we report a 29-year-old Iranian man with abdominal pain, diarrhea, hearing loss, ophthalmoplegia, sensorimotor axonal neuropathy, and elevated muscle enzymes. Magnetic resonance imaging showed leukoencephalopathic changes. Metabolite analysis revealed a very high thymidine concentration in the patient's urine consistent with the diagnosis of mitochondrial neurogastrointestinal encephalomyopathy