Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis.

BACKGROUND: The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown. METHODS: We conducted systematic search on the PubMed, SCOPUS, and Embase databases from inception to December 2020 for clinical studies that compared the fixed-dose versus variable-dose of 4-PCC for VKAs reversal with at least one reported clinical outcome. The treatment effects were expressed as relative ratios (RR) with 95% confidence intervals (CIs) and pooled by a random-effects model. RESULTS: Ten studies, including 988 patients, were included. Fixed-dose 4-PCC was associated with lower rate of mortality (RR= 0.65, 95% CI 0.47 to 0.9, p= 0.009), comparable rate of thromboembolic event (TEE) (RR= 1.10, 95%CI 0.44 to 2.80, p= 0.826), and lower goal INR reached (RR= 0.87, 95%CI 0.78 to 0.96, p= 0.007). Less 4-PCC cumulative dose, shorter duration of order-to-needle time, similar hospital length of stay, the comparable time required for INR reversal, higher post-4-PCC INR, and a higher need for additional dose were observed in fixed-dose. CONCLUSIONS: The use of a fixed-dose of 4-PCC may be considered an effective and safe dosing strategy for VKAs reversal in various clinical situations. However, further well-designed, controlled studies should be conducted focusing on clinical outcomes to determine the optimal dose of 4-PCC for VKAs reversal.

Cardiovascular Complications of COVID-19: Pharmacotherapy Perspective.

Coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly the world over. The disease was declared "pandemic" by the World Health Organization. An approved therapy for patients with COVID-19 has yet to emerge; however, there are some medications used in the treatment of SARS-CoV-2 infection globally including hydroxychloroquine, remdesivir, dexamethasone, protease inhibitors, and anti-inflammatory agents. Patients with underlying cardiovascular disease are at increased risk of mortality and morbidity from COVID-19. Moreover, patients with chronic stable states and even otherwise healthy individuals might sustain acute cardiovascular problems due to COVID-19 infection. This article seeks to review the latest evidence with a view to explaining possible pharmacotherapies for the cardiovascular complications of COVID-19 including acute coronary syndrome, heart failure, myocarditis, arrhythmias, and venous thromboembolism, as well as possible interactions between these medications and those currently administered (or under evaluation) in the treatment of COVID-19.

Comparison of the Effects of Melatonin and Oxazepam on Anxiety Levels and Sleep Quality in Patients With ST-Segment-Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention: A Randomized Clinical Trial.

BACKGROUND: Anxiety and sleep disorders are prevalent problems in patients presenting with ST-segment-elevation myocardial infarction (STEMI). Usually, these problems are managed by benzodiazepines, which-albeit effective-could cause adverse effects and drug interaction. OBJECTIVE: This study was designed to compare the effects of melatonin and oxazepam in the management of anxiety and insomnia on patients following primary percutaneous coronary intervention (PCI) with a view to providing a safer alternative. METHODS: This study was designed as a randomized clinical trial. STEMI patients managed with primary PCI were enrolled and randomized into 2 groups through the permuted block randomization. The patients received either oxazepam (10 mg) or melatonin (3 mg) every night. Autoimmune disease or previous use of psychoactive medications was considered the exclusion criterion. Levels of anxiety and sleep quality were evaluated using the Hamilton Anxiety Rating Scale (HAM-A) and the Groningen Sleep Quality Score and compared between the groups. RESULTS: Each group contained 20 patients. Melatonin showed a significant advantage over oxazepam in improving sleep quality ( P = 0.040). Comparisons of the efficacy of both medications in lowering the anxiety levels when considering all the items of the HAM-A, including those related to cardiovascular disease, were significantly in favor of melatonin ( P = 0.019). CONCLUSIONS AND RELEVANCE: The results of this study suggest that melatonin, a drug with more favorable drug interaction and adverse effect profile, could be more effective than oxazepam in improving the sleep quality and anxiety levels of patients presenting with STEMI, and it could be considered a new alternative to benzodiazepines in this setting.

Effect of High-Dose Allopurinol Pretreatment on Cardiac Biomarkers of Patients Undergoing Elective Percutaneous Coronary Intervention: A Randomized Clinical Trial.

BACKGROUND: Increased accumulation of reactive oxygen species contributes to pathophysiologic states such as endothelial dysfunction, metabolic and functional impairment, inflammatory activation, and other features of cardiovascular pathophysiology. Allopurinol acts as a xanthine oxidase inhibitor that reduces the amount of free radicals after reactive oxygen species generation. METHODS AND RESULTS: In this placebo-controlled randomized clinical trial, all patients admitted with coronary artery disease who are candidates for elective percutaneous coronary intervention (PCI) were included. The 254 patients were randomly divided into 2 groups. Blood samples for cardiac biomarkers (creatine kinase [CK]-MB and troponin T [cTnT]) were collected from all patients after admission (the day before PCI), and also 8 and 16 hours after intervention. In group 1 (133 patients), 600 mg allopurinol was orally administered on the day before PCI, and another same dose on the day of PCI, and the elective PCI was performed. In group 2 (121 patients), elective PCI was performed without pretreatment with allopurinol. In an unadjusted model, the serum levels of both CK-MB and cTnT, 16 hours after PCI were higher in the placebo group as compared with the allopurinol group, although it was statistically insignificant. We compared the maximum levels of CK-MB and cTnT (8 or 16 hours after PCI) and their maximum changes in both groups. After adjustment for confounders, use of allopurinol did not have any statistically significant association with the rise of cardiac-spec-fic enzymes. CONCLUSIONS: Allopurinol could not be effective significantly, in patients undergoing elective PCI, to decrease cardiac-specific enzymes, and seems not to be of use before PCI.

Evaluating the Effect of Intracoronary N-Acetylcysteine on Platelet Activation Markers After Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction.

During percutaneous coronary intervention (PCI), trauma occurs in the arterial endothelium, resulting in platelet activation and aggregation. As platelet aggregation may lead to coronary thrombosis, antiplatelet agents are essential adjunctive therapies in patients undergoing PCI. The aim of this study was to determine the effect of the intracoronary administration of high-dose N-acetylcysteine (NAC) for the evaluation of its antiplatelet effects in human subjects. In this triple-blind trial, 147 patients undergoing primary PCI were enrolled. Finally, 100 patients were randomized to receive high-dose intracoronary NAC (100 mg/kg bolus, followed by 10 mg·kg⁻¹·h⁻¹ intracoronary continued intravenously for 12 hours) (n = 50) or dextrose solution (n = 50). Platelet activation biomarkers were measured before and 24 hours after the procedure. Secondary end points, comprising all-cause death, reinfarction, and target-vessel revascularization, were assessed at 30 days and 2 years. In comparison with the placebo, NAC could not reduce the level of platelet activation biomarkers within a 24-hour period after its prescription. Major adverse clinical events at 30 days and 2 years were infrequent and not statistically different between the 2 groups. Our results revealed that NAC, compared with the placebo, did not provide an additional clinical benefit as an effective antiplatelet agent after PCI.

Comparison of the effects of N-acetyl-cysteine and ginseng in prevention of noise induced hearing loss in male textile workers.

Previous studies revealed the role of antioxidant agents in prevention of noise induced hearing loss (NIHL). The aim of this study was to compare the protective effect of N-acetyl-cysteine (NAC) and ginseng on protection of NIHL in textile workers exposed to continuous noise in daily working. In this study, 48 participants were randomly allocated to three groups; Group I received NAC 1200 mg/day, Group II received ginseng 200 mg/day, and Group III (control group) received no supplement. Pure tone audiometry and high frequency audiometry were performed preshift before and after 14 days (on day 15). Linear regression analysis results showed reduced noise-induced temporary threshold shift (TTS) for NAC and ginseng groups at 4, 6 and 16 kHz (P < 0.001) in both ears. Furthermore, the protective effects were more prominent in NAC than ginseng. Our results show that NAC and ginseng can reduce noise induced TTS in workers exposed to occupational noise. Further studies are needed to prove antioxidants benefits in hearing conservation programs.

Colorectal cancer targeted Irinotecan-Assam Bora rice starch based microspheres: a mechanistic, pharmacokinetic and biochemical investigation.

The purpose of this investigation was to evaluate the colon-targeted Irinotecan Hydrochloride (ITC-HCl) loaded microspheres by pharmacokinetic and biochemical studies. The microspheres were prepared by double emulsion solvent evaporation method with natural polymer Assam Bora rice starch. The microspheres were characterized for their micromeritics properties, incorporation efficiency, in vitro and in vivo drug release studies. The release study confirmed the insignificant release of ITC-HCl in physiological condition of stomach and small intestine and major drug release in the caecal content. In vivo release study of the optimized microsphere was compared with immediate release (IR) ITC-HCl. ITC-HCl was distributed predominantly in the upper GI tract from the IR, whereas ITC-HCl was distributed primarily to the lower part of GI tract from the microspheres formulation. Enhanced levels of liver enzymes were found in animals given IR ITC-HCl as well as augmented levels of serum albumin, creatinine, leucocytopenia and thrombocytopenia was also observed. In summary, Assam Bora rice starch microspheres exhibit slow and extended release of ITC-HCl over longer periods of time with reduced systemic side-effects.

Sodium-glucose cotransporter 2 inhibitors: A comprehensive review from cells to bedside.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) are oral medications approved for type 2 diabetes mellitus. Interestingly, during recent years, they have been promisingly considered as new medications for cardiovascular and kidney diseases. However, the mechanisms underlying these new benefits are not fully understood. Thanks to the discovery of multiple modes of action, the simple picture about mechanisms of action of SGLT2is has become more and more complex. Besides their effects in diabetes, there is increasing evidence for their beneficial effects in heart failure and chronic kidney diseases. In addition, many studies have provided evidence for the fruitful effects of SGLT2is in atherosclerotic cardiovascular disease. In this study, we present mounting evidence for the complex action modes of SGLT2is and their current applications in clinical practice.

Plasma vitamin C concentrations in patients on routine hemodialysis and its relationship to patients' morbidity and mortality.

BACKGROUND: Some studies have hypothesized the protective role of vitamin C against cardiovascular disorders (CVD) in patients with end-stage renal disease (ESRD). This study was designed to assess plasma vitamin C concentration and its relationship to hemodialysis (HD) patients' morbidity and mortality. METHODS: Plasma vitamin C concentrations were assessed in HD patients using spectrophotometry and subjects were prospectively followed for up eighteen months for all-cause mortality. Any association between vitamin C concentration and patients' demographic data, co-morbidities, or the cause of ESRD were investigated using the Chi-square test. RESULTS: Ninety-one patients with a mean age of 56.7 ± 15.7 years were included in this study. The most frequent cause of ESRD was simultaneous hypertension and diabetes in 30 % of patients, followed by hypertension in 25.6 %, and diabetes in 11.1 %, respectively. About 34 % of patients had CVD as the most prevalent co-morbidity. Forty-nine patients (53.8 %) had low levels of vitamin C concentration. There was a significant relationship between vitamin C insufficiency and presence of any co-morbidity in HD patients (p < 0.05). There was a significant difference in vitamin C concentrations between patients without co-morbidities and those with cardiovascular ones (F[2,88]=3.447, p = 0.036). Twenty-two (24.2 %) patients died over a median duration of 227 days. There was a significant difference in time to death of patients with and without low levels of vitamin C concentration (p = 0.04). CONCLUSIONS: The results showed lower plasma vitamin C levels in HD patients who suffered any co-morbidity and sooner time to death in these patients.

The No-reflow Phenomenon: Is it Predictable by Demographic factors and Routine Laboratory Data?

BACKGROUND: The coronary no-reflow phenomenon is an adverse complication of percutaneous coronary interventions (PCI) which significantly worsens the outcome and survival. In this study, we have evaluated the correlation of no-reflow phenomenon with demographic, biochemical and anatomical factors. METHODS: We included 306 patients (193 male) with acute ST-elevation myocardial infarction (STEMI) who undergone primary PCI in our center. Demographic factors, as well as biochemistry test results were obtained. Also, the Thrombolysis in Myocardial Infarction (TIMI) grade and TIMI frame count (TFC) was measured. The correlation of no-reflow phenomenon with demographic, biochemical and anatomical factors was analyzed. RESULTS: Patients with a mean age of 56.41 ± 11.8 years were divided into two groups depending on the TIMI score (Group 1 or Normal flow and Group 2 or No-reflow). Symptom-to-procedure time, door-to-procedure time, serum creatinine level, hs-CRP level, and Neutrophil to Lymphocyte Ratio (NLR) were significantly higher among group 2. TFC had negative significant correlation with male gender, and positive significant correlation with age, diabetes mellitus, hs-CRP level, WBC count, and NLR. Age of more than 62.5 years and serum creatinine level of more than 0.89 mg/dL can optimally predict the no reflow phenomena. CONCLUSIONS: According to our results, it seems that female gender, older ages, DM, multi-vessel involvement, delayed reperfusion, and increased NLR can predict the risk of no-reflow after primary PCI in the setting of Acute Myocardial Infarction.

Tribulus terrestris-induced severe nephrotoxicity in a young healthy male.

Herbal medications are being progressively utilized all over the world. Nevertheless, herbal remedies are not without hazards and several cases of adverse reactions have been described. Tribulus terrestris is traditionally used because of its aphrodisiac and antiurolithiatic activities with almost complete inhibition of stone formation. We report a case of T. terrestris-induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient who used the plant's extract to prevent kidney stone formation. He presented with seizure and very high serum aminotransferases and creatinine after consuming herbal water for 2 days. Discontinuation of the herbal remedy resulted in improvement in symptoms and normalization of his liver enzymes.

Is deep vein thrombosis prophylaxis appropriate in the medical wards? A clinical pharmacists' intervention study.

OBJECTIVE: Venous thromboembolism is a major cause of mortality and morbidity in hospitalized patients. To evaluate physicians' approach to patients' thrombosis risk assessment and practice of thromboembolism prophylaxis in a teaching hospital, we designed an interventional prospective study. SETTING: This pre and post interventional study was conducted in the infectious diseases ward of Imam Khomeini referral hospital, Tehran, Iran. METHOD: Patients' risk factors for thromboembolism during hospitalization course and physicians' thromboembolism prophylaxis approaches were evaluated in a pre and post clinical pharmacists' interventional study. MAIN OUTCOME MEASURE: An internal guideline for prescribing anticoagulants as deep vein thrombosis (DVT) prophylaxis was prepared by clinical pharmacists and the appropriateness of anticoagulants' prescription was evaluated and compared before and after the implementation of consensual guideline. RESULTS: In the pre-intervention phase 69.9% of patients had appropriate indication and received thromboembolism prophylaxis and in 31.1% of enrolled patients anticoagulants were prescribed inappropriately. Prescription of anticoagulants was appropriate in 88.4% of patients during the post interventional phase of the study while 11.6% of admitted patients received prophylaxis improperly. A decrease in the number of patients who had the criterion for DVT prophylaxis but anticoagulants were not administered after the implementation of internal guideline was statistically significant (P=0.001). CONCLUSION: The implementation of clinical pharmacists' prepared protocol helped to a great extent in the improvement of administrating DVT prophylaxis appropriately in patients.

S2P peptide-conjugated PLGA-Maleimide-PEG nanoparticles containing Imatinib for targeting drug delivery to atherosclerotic plaques.

BACKGROUND: Imatinib is a platelet-derived growth factor receptor (PDGFR) inhibitor with very low water solubility. Previous studies in atherosclerosis have shown that PDGFR activity has an egregious effect on vascular disease and progression of atherosclerosis. Specific ligands of atherosclerotic plaques can be used for targeting of nanoparticles. Studies in atherosclerosis proved that stabilin-2 is a glycoprotein which exists abundantly in atherosclerotic plaques and it is produced from both macrophages and endothelial cells. OBJECTIVES: The objective of this study is the targeting drug delivery to atherosclerotic plaques by using imatinib-loaded nanoparticles modified by S2P peptide. METHODS: The imatinib-loaded nanoparticles were fabricated through a modified emulsion/solvent evaporation technique. After fabricating PLGA nanoparticles, maleimide PEG was used as linker between PLGA nanoparticles and S2P peptide. Because of presence cysteine in both side of S2P peptide, maleimide formed a thiolether linkage by thiol group of cysteine. Then the physicochemical analysis like H-NMR, FT-IR, DSC, SEM, particle size, zeta potential, and drug release were studied. RESULTS: Stabilin-2 peptide with sequence of CRTLTVRKC is a specific ligand to stabilin-2, so it was synthesized for using as the targeting agent for atherosclerosis. S2P peptide conjugation to the surface of nanoparticles was proved by H-NMR and FT-IR, and the percentage of S2P peptide in nanoparticles was 1.3%. The final nanoparticles were spherical and their size were 183 nm. The loading capacity of the imatinib-loaded nanoparticles was 5.05%. The sustained release profile was observed for peptide targeted nanoparticles. CONCLUSION: The chosen method was simple, reproducible, and specific in peptide conjugation of nanoparticles for targeting delivery to atherosclerotic regions. Graphical abstract .

Potential Role of Vitamin C Intracoronary Administration in Preventing Cardiac Injury After Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction.

OBJECTIVE: The aim of the present study was to determine the effects of intravenous (IV) and intracoronary administration of Vitamin C on the incidence of periprocedural myocardial injury in patients undergoing primary percutaneous coronary intervention (PCI). METHODS: In this prospective, double-blind, randomized clinical trial, that was conducted in Tehran Heart Center, Iran, between October 2016 and March 2017, 252 patients undergoing primary PCI were enrolled to receive either 3 g of IV Vitamin C before PCI and 100 mg of intracoronary Vitamin C during PCI in addition to the routine treatment (n = 126) or just the routine treatment (n = 126). Cardiac biomarkers were measured before and then 6 and 12 h postprocedurally. We determined the occurrence of contrast-induced acute kidney injury (CI-AKI), according to the levels of serum creatinine, neutrophil gelatinase-associated lipocalin, and platelet activation biomarker (P-selectin) in a subset of 119 patients before and 6 h after PCI. FINDINGS: In the patients who received Vitamin C, the serum levels of troponin T after 12 h and creatine kinase-MB after 6 h were significantly lower than those in the placebo group (P = 0.003 andP = 0.00, respectively). CI-AKI occurred in 6 (4.7%) patients in the study group and 8 (6.3%) patients in the control group; there was no significant reduction in CI-AKI in the study group. In addition, the two groups were statically similar as regards the changes in the level of P-selectin. CONCLUSION: In primary PCI patients, the prophylactic use of IV and intracoronary Vitamin C can confer additional clinical benefits such as cardioprotection.

Two-year Follow-up of Patients With Unstable Angina/Non-ST Segment Elevation Myocardial Infarction Undergoing Early Invasive Strategy: Predictors of Normal or Near-Normal Coronary Angiography and Mortality.

BACKGROUND: Predictors of normal or near-normal coronary angiography (NONCAG) in patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) and their importance regarding the prognosis are not understood. Accordingly, we determined these predictors as well as mortality risk factors at 2-year follow-up of UA/NSTEMI patients managed by the early invasive strategy. METHODS: We prospectively studied consecutive patients with UA/NSTEMI managed with the early invasive strategy at Tehran Heart Center, in 1-year period. Echocardiography was performed before coronary angiography (CAG) for all the patients. Baseline characteristics, laboratory parameters, echocardiographic findings, invasive treatment modalities, and survival status after 2 years of follow-up were collected. We identified the predictors of NONCAG in the first phase of the study and then the risk factors of mortality in the second phase. RESULTS: In the study period, 298 patients including 211 (71%) males, with the age of 59.31 ± 10.72 years were enrolled. The following factors were predictors of NONCAG: the female sex (P < 0.001); negative family history of CAD (P = 0.028); Thrombolysis in Myocardial Infarction (TIMI) risk score (P < 0.001); and early transmitral flow velocity/mean mitral annular velocity (E/E'mean) (P = 0.003). The following items were significant protective factors against mortality: percutaneous coronary intervention (PCI) (P = 0.012), age (P = 0.001), and E/E'mean (P = 0.020). CONCLUSION: Patients' baseline characteristics as well as echocardiographic data could help in predicting those with NONCAG and PCI can be considered as the treatment of strategy with the most protection against mortality.

Randomized Trial of Carnitine for the Prevention of Perioperative Atrial Fibrillation.

Atrial fibrillation (AF) is one of the most common complications in patients who undergo coronary artery bypass graft surgery (CABG). The aim of this study was to evaluate the effect of L-carnitine administration on postoperative AF and the levels of C-reactive protein (CRP) following CABG. The effects of L-carnitine on the incidence of acute kidney injury after CABG were also assessed. One hundred thirty-four patients undergoing elective CABG, without a history of AF or previous L-carnitine treatment, were randomly assigned to an L-carnitine group (3000 mg/d L-carnitine) or a control group. CRP levels, as a biomarker of inflammation, were assessed in all the patients before surgery as baseline levels and 48 hours postoperatively. Neutrophil gelatinase-associated lipocalin, as a kidney biomarker, was also measured in the patients before surgery and 2 hours thereafter. The incidence of AF was 13.4% in our population. The incidence of AF was decreased in the L-carnitine group (7.5% in the L-carnitine group vs 19.4% in the control group; P = 0.043) and the postoperative CRP level (8.79 ± 6.9 in the L-carnitine group, and 10.83 ± 5.7 in the control group; P = 0.021). The postoperative neutrophil gelatinase-associated lipocalin concentration demonstrated no significant rise after surgery compared with the preoperative concentration (72.54 ± 20.30 in the L-carnitine group vs 67.68 ± 22.71 in the placebo group; P = 0.19). Our study showed that L-carnitine administration before CABG might inhibit and reduce the incidence of AF after CABG. It seems that a rise in the CRP level, as an inflammation marker, may be associated with the incidence of AF. Inflammation as measured by CRP was also reduced in the carnitine group, compared with the control group.

Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center.

BACKGROUND: Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but-to the best of our knowledge-few studies have assessed this. OBJECTIVES: Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. METHODS: We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100 mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC 10 mg/kg for 12 h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC). RESULTS: The peak CK-MB level was comparable between the two groups (P = 0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P = 0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P = 0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG. CONCLUSIONS: In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population. ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; http://irct.ir ) registration number: IRCT201301048698N8.

Effect of memantine on post-operative cognitive dysfunction after cardiac surgeries: a randomized clinical trial.

BACKGROUND: Post-operative cognitive dysfunction (POCD) is an important complication of cardiac surgeries. Glutamate plays a critical role in physiologic and pathologic conditions in the brain. Due to the role of glutamate in ischemia, this study is designed to identify the effect of memantine in prevention of POCD early and late after cardiac surgeries. METHODS: In this randomized clinical trial, 172 patients with ages 45-75 years old who underwent elective cardiac surgery were enrolled. For patients in memantine group, 5 mg of memantine per day administered at least 48 h before surgery and increased to 10 mg per day during the first 24 h after surgery and continued for 3 months. A brief Wechsler memory test (WMT) was administered before, three to 5 days after, and 3 months after surgery for both groups. RESULTS: Both groups demonstrate standard pattern of cognitive dysfunction after surgery and in follow up. Pre- and post-operative WMT score showed significant improvement in memantine compared to control group (P < 0.001) both in unadjusted and adjusted with confounding factor analysis. Unadjusted pre-, post-operative, and follow up WMT score improved significantly after 3 months in memantine group (P = 0.006). CONCLUSION: Pre-operative administration of memantine protects patients from POCD following cardiac surgeries. In addition, it improves cognitive function 3 months after surgery. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (registration number: IRCT201303168698N12 ). Memantin effect on POCD.

Potential Role of Allopurinol in Preventing Contrast-Induced Nephropathy in Patients Undergoing Percutaneous Coronary Intervention: A Randomized Placebo-Controlled Trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is a major drawback in percutaneous coronary intervention (PCI). Significant uricosuria has been reported following contrast exposure. Allopurinol-a xanthine oxidase inhibitor-has been suggested to prevent the formation of oxygen-free radicals, which may contribute to CIN. The aim of the present study was to evaluate the possible efficacy of allopurinol in preventing CIN. METHODS: In this double-blind placebo-controlled trial, patients with an estimated glomerular filtration rate ≥60 mL/min who were admitted for elective PCI, were randomized to receive either allopurinol 600 mg or a placebo administered 24 h before the procedure, and again immediately before the procedure. Blood samples were drawn at 24 h before and 24 h after contrast exposure to measure serum creatinine (SCr), uric acid, and serum cystatin-c. RESULTS: The baseline characteristics were almost similar between the placebo and allopurinol groups. The overall change in SCr and the rate of CIN, which is defined as ≥25% increase in serum cystatin-c relative to baseline, failed to show a significant difference between the two groups. When adjusted on the baseline cystatin-c, SCr, sex, and positive family history, the difference in the overall increase in serum cystatin-c was statistically significantly lower in the allopurinol group. CONCLUSIONS: Allopurinol administration in patients undergoing PCI failed to show efficacy in preventing CIN. Nevertheless, this effect should be further evaluated in the patient population with chronic kidney disease.

The Role of N-Acetylcysteine in Platelet Aggregation and Reperfusion Injury in Recent Years.

BACKGROUND: N-acetylcysteine (NAC) is an amino acid that contains a cysteine group and is currently used widely in various fields of medical research especially in cardiology. In this review, potential benefits of NAC in the aggregation of platelet and reperfusion injury are evaluated. METHODS: The available evidence was collected by searching Scopus, Pub-Med, Medline, Cochrane central register of controlled trials, and Cochrane database systematic reviews. Our searching was performed without time limitation and only English language articles were included in this review. Key words used as search terms included "N-acetylcysteine", "platelet aggregation", "reperfusion injury". RESULTS: Over the past decade, several investigations were carried out to ascertain reperfusion injury and antiplatelet properties of NAC, and in this article the results of investigations in both models (human and animal) were addressed in detail. The results revealed that NAC has an important antiplatelet property in animal models while this effect is not very significant in human models and needs more investigations. However, its reperfusion injury in both models is worth noticing. CONCLUSION: Due to the limited data about effectiveness of NAC in both human and animal as antiplatelet agent, more investigation is needed to evaluate NAC efficacy in platelet aggregation and reperfusion injury especially in human studies in the future.