Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

Investigation of pharmacokinetic and clinical outcomes of various meropenem regimens in patients with ventilator-associated pneumonia and augmented renal clearance.

INTRODUCTION: Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC. MATERIALS AND METHODS: In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days. RESULTS: Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement. CONCLUSION: According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients.

Study of the Effects of N-acetylcysteine on Inflammatory Biomarkers and Disease Activity Score in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is considered as an autoimmune-related condition in which the overproduction of pro-inflammatory cytokines leads to an inflammatory cascade. N-acetylcysteine (NAC) is a potent anti-inflammatory and anti-oxidant agent. We aimed to explore the impact of oral NAC on cytokines activities and clinical indicators in RA patients. In this placebo-controlled randomized double-blind clinical trial, 41 active RA patients were allocated in either NAC (600 mg, twice a day) or placebo group, as add-on therapy to the routine regimen, for 8 weeks. Disease activity score with an erythrocyte sedimentation rate (DAS28-ESR), and serum concentrations of interleukin (IL)-1ß and IL-17 were assessed at baseline and end of the trial for all participants in the test and control groups. The reduction of the DAS28-ESR was higher considerably in the NAC group compared to that of the control group. No statistically significant differences were seen in the reduction of IL-1ß and IL-17 cytokines between the NAC and control groups. In addition, improvements in the patient global assessment, number of tender joints, number of swollen joints, and the ESR rates were in favor of the NAC group. Our findings reveal that NAC may have a beneficial effect on all of the clinical features of RA. However, non-significant variations in the IL-1ß and IL-17 levels suggest an alternative way of NAC effectiveness without influencing the measured cytokines. Nevertheless, these results need to be confirmed by further investigations.

Simultaneous Analysis of 10 Priority PAHs in Iranian Sangak Bread Samples by Developing a GC-MS Method.

Human exposure to polycyclic aromatic hydrocarbons (PAHs) is known as a carcinogen risk factor. In this study, a gas chromatography-mass spectrometry (GC-MS) technique combined with the QuEChERS extraction method was developed for concurrent analysis of 10 polycyclic aromatic hydrocarbons (PAHs) in Iranian traditional Sangak bread samples. The method was validated by determining different parameters, including; linearity, accuracy, precision, limit of detection (LOD) and limit of quantitation (LOQ). Calibration curves showed a linear relationship in the concentration range of 10-500 ng/g with a coefficient of determination (R2) ranged between 0.994 and 0.999. The obtained mean recoveries were 92-106% with the relative standard deviations (RSDs) in the range of 3-7% with an acceptable precision (RSD < 20%). The Limit of detections (LODs) for different PAHs were between 0.14-0.78 ng/g, while the limit of quantitation (LOQ) was 0.46-2.60 ng/g. Matrix effect studies showed that the analytes concluded signal suppressions or enhancements. Therefore, spiked calibration curves were used for overcoming this issue. The result of Sangak bread samples analysis using the validated method showed that 9 (19.4%) out of 47 Sangak bread samples were contaminated with phenanthrene (PHE) and anthracene (ANT) at the mean level of 10.08 ± 6.38 ng/g which were higher than the permissible limit of European Commission regulatory control value for BaP (1 µg/kg of wet weight) in processed cereal-based foods and baby foods for infants and young children.

Development of A Liquid Chromatography-Mass Spectrometry Technique for Evaluation of Multi-class Pesticides in Rice Samples.

In the current study, a liquid chromatography coupled mass detector was set up to detect and quantify 108 pesticide residues in rice samples. QuEChERS method was applied for sample preparation and different validation parameters were determined to ensure the suitability of the method. The calibration curves were linear in the concentration 0.01-1.00 mg/kg with a coefficient of determination (R2) of more than 0.990 for all compounds. Based on signal to noise studies, the calculated LODs and LOQs were 0.005-0.060 mg/kg and 0.018-0.199 mg/kg, respectively; and acquired mean recoveries at three spiked levels (0.025, 0.200 and 0.800 mg/kg) were 72% - 117% with RSD < 20%. The developed method was used to investigate the occurrence of the studied pesticides in 65 internal and 65 foreign rice samples. The results showed that 14 internal and 15 imported samples were found to be contaminated 12 pesticides in the amounts between 0.027 mg/kg to 0.078 mg/kg and 0.031 mg/kg to 0.081 mg/kg, respectively. According to the Iranian regulations, with the exception of nine prohibited pesticides for rice production in Iran, bioallethrin, cypermethrin, deltamethrin, flutriafol, foramsulfuron, imazalil, phosphamidon, TCMTB, and triasulfuron, three permitted pesticides, cinosulfuron, triadimenol, and tricyclazole, found in positive rice samples were below MRLs established by Iranian National Standard Organization (INSO).

The Evaluation of Melatonin Effects on Mobilization and Engraftment in Autologous Hematopoietic Stem Cell Transplant Recipients; A Randomized, Double-blind and Placebo-controlled Trial.

Mobilization and engraftment of Hematopoietic Stem Cells (HSCs) are challenging issues in Autologous HSC transplantation (AHSCT) so several attempts such as colony-stimulating factors (CSF) and plerixafor have been used for enhancement of HSCs mobilization and engraftment. In this randomized, double-blind and placebo-controlled study, we evaluated the melatonin's efficacy and safety, as endogenous CSF inducer, co-administered with Filgrastim in mobilizing and engraftment of HSC. AHSCT patients were randomized to receive either Melatonin or placebo plus filgrastim. Of Fifty-one patients, 26 patients received the melatonin (In mobilization phase 3 mg sublingual twice daily, then 9 mg single dose 30 min before apheresis session and then 3 mg twice daily from +1 until engraftment) and 25 patients received the placebo. The mean number of CD34 cells/kg × 106 in the melatonin group was 6.54 versus 4.22 in the placebo group (p = 0.025). The mean day to neutrophil engraftment in the melatonin group was 11.69 ± 2.093, whereas 12.68 ± 2.42 days in the placebo group (p = 0.021). In this study, the second apheresis session requirement, the use of plerixafor and hospital stay duration, were comparable between the two groups. Considering the result of the study, it could be suggested that melatonin plus Filgrastim can be effectively used in AHSCT patients to enhance the number of peripheral CD34 cells/kg × 106 and decrease the day number of neutrophil engraftment.

Development of a Sensitive and Rapid Method for Determination of Acrylamide in Bread by LC-MS/MS and Analysis of Real Samples in Iran IR.

A new sample preparation procedure and a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method were developed for the quantitative analysis of acrylamide in bread. The method is based on sample extraction in methanol, purification with Carrez solutions and clean- up with Primary Secondary Amine (PSA).The developed method offers an efficient, inexpensive, easy sample preparation and very sensitive procedure for determination of acrylamide in bread. The use of spiked calibration curves for constructing the calibration curve substantially reduced adverse matrix-related effects. Recoveries were between 96 and 105.3%. Good results were obtained with respect to repeatability (RSDs <11%). The limit of detection and quantification of the method was 0.3 and 1 ng/g, respectively, which shows the method is very sensitive. The developed method was used for the determination of acrylamide in 26 traditional bread samples (Sangak) collected from Shiraz. The results showed that about 96% of Sangak bread samples were contaminated with acrylamide that 64.3 and 33.3 of semi-industrial and traditional Sangak bread were higher than benchmark levels (50 µg/kg), respectively. There are a few reports concerning contamination of Sangak bread samples with acrylamide in Iran. Therefore, this method could be used for a comprehensive survey of acrylamide in Sangak bread samples in the country.

Promising effects of tocilizumab in COVID-19: A non-controlled, prospective clinical trial.

BACKGROUND: The clinical presentation of SARS-CoV-2 infection ranges from mild symptoms to severe complications, including acute respiratory distress syndrome. In this syndrome, inflammatory cytokines are released after activation of the inflammatory cascade, with the predominant role of interleukin (IL)-6. The aim of this study was to evaluate the effects of tocilizumab, as an IL-6 antagonist, in patients with severe or critical SARS-CoV-2 infection. METHODS: In this prospective clinical trial, 76 patients with severe or critical SARS-CoV-2 infection were evaluated for eligibility, and ultimately, 42 patients were included. Tocilizumab was administered at a dose of 400 mg as a single dose via intravenous infusion. Primary outcomes included changes in oxygenation support, need for invasive mechanical ventilation, and death. Secondary outcomes included radiological changes in the lungs, IL-6 plasma levels, C-reactive protein levels, and adverse drug reactions. The data were analyzed using SPSS software. RESULTS: Of the 42 included patients, 20 (48%) patients presented the severe infection stage and 22 (52%) were in the critical stage. The median age of patients was 56 years, and the median IL-6 level was 28.55 pg/mL. After tocilizumab administration, only 6 patients (14%) required invasive ventilation. Additionally, 35 patients (83.33%) showed clinical improvement. By day 28, a total of 7 patients died (6 patients in the critical stage and 1 patient in the severe stage). Neurological adverse effects were observed in 3 patients. CONCLUSIONS: Based on the current results, tocilizumab may be a promising agent for patients with severe or critical SARS-CoV-2 infection, if promptly initiated during the severe stage.

A comparative study of the analgesic effects of intravenous ketorolac, paracetamol, and morphine in patients undergoing video-assisted thoracoscopic surgery: A double-blind, active-controlled, randomized clinical trial.

Background: Opioids are traditionally used as the drug of choice for the management of postoperative pain. However, their use is limited in patients undergoing Video-assisted thoracic surgery (VATS), due to their side effects, such as respiratory depression, nausea, and vomiting. Aim: In this double-blind active-controlled randomized study, we have compared the analgesic effects of ketorolac and paracetamol to morphine. Methods: Patients were randomly chosen from a pool of candidates who were undergoing VATS and were divided into three groups. During the first 24 h postsurgery, patients in the control group received a cumulative dose of morphine 20 mg, while patients in two treatment groups received ketorolac 120 mg and paracetamol 4 g in total. Doses were administered as bolus immediately after surgery and infusion during the first 24 h. Patients' pain severity was evaluated by visual analogue scale rating (VAS) at rest and during coughing episodes. Results: The average pain score at recovery time was 2.29 ± 2.13 and 2.26 ± 2.16 for ketorolac and paracetamol, respectively, and it was significantly lower than the morphine group with an average pain score of 3.87 (P = 0.003). Additionally, the VAS score during cough episodes was significantly higher in the control group throughout the study period compared to study groups. Comparison of mean morphine dose utilized as liberation analgesic (in case of patients had VAS >3) between three groups was not significantly different (P = 0.17). Conclusion: Our study demonstrates the non-inferiority of ketorolac and paracetamol to morphine in controlling post-VATS pain without causing any significant side effects. We also show that ketorolac and paracetamol are superior to morphine in controlling pain during 2 h postsurgery.

Comparison of Mirtazapine and Olanzapine on Nausea and Vomiting following Anthracycline-cyclophosphamide Chemotherapy Regimen in Patients with Breast Cancer.

We evaluated and compared the efficacy and safety of mirtazapine (MTZ) with olanzapine (OLP) for preventing chemotherapy-induced nausea and vomiting (CINV) following anthracycline plus cyclophosphamide (AC) regimen. Eligible participants were chemotherapy-naive early-stage breast cancer patients who were scheduled to undergo adjuvant AC. The patients were randomized to take oral MTZ or OLP in combination with aprepitant (A), dexamethasone (D), and granisetron (G), (ADG). The endpoints included rates of complete response (CR), complete control (CC), total control (TC), and adverse events during the acute, delayed, and overall phases in the two cycles of chemotherapy. The influence of CINV on the quality of life (QoL) was evaluated on day 6 of chemotherapy. Of 82 patients, 60 were randomized. In the first cycle, CR rates in cycle 1 were 83.3% and 76.6% during the acute period, 80% and 86.6% during the delayed period, and 66.6% and 63.3% during the overall period, for the ADG-M and ADG-O, respectively. High efficacy of both groups was maintained over 2 cycles. More patients in the ADG-M group noted minimal or no impact of CINV on daily life in cycle 2 (89.7% vs. 67.9%; p = 0.044). Incidence of somnolence and fatigue was more frequent with the olanzapine group. In this study, there was no substantial difference between mirtazapine and olanzapine in preventing CINV. Further large randomized trials are essential to demonstrate the anti-emetic effect of mirtazapine in chemotherapy.

Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) is associated with increased inflammatory responses to noxious particles, which can be further enhanced during Acute Exacerbation of COPD (AECOPD). Considering the important immunoregulatory function of vitamin D, high prevalence of Vitamin D Deficiency (VDD) in COPD patients and a negative link between vitamin D levels and inflammatory biomarkers, suggests the seemingly interesting mechanism of vitamin D effects on inflammation resolution during the conventional treatment of AECOPD. The admitted AECOPD patients with VDD were recruited and randomly allocated to receive either 300,000 IU of intramuscular vitamin D (n = 35) or placebo (n = 35). Primary outcomes included inflammation resolution dynamics, which were assessed by monitoring the serum levels of IL-6, IL-8, and hs-CRP. Symptom recovery was evaluated based on the modified Medical Research Council (mMRC) dyspnea scale on the 1st and 6th days of admission. Secondary outcomes included the length of hospital stay (LOS) and 30-day mortality rates. Inflammatory biomarkers were highest at Day 1. Baseline vitamin D levels were 11.25 ± 3.09 and 10.59 ± 3.90 ng/ml (P = 0.45), which reached 11.35 ± 3.16 and 18.17 ± 4.24 by Day 6 (P < 0.001) in the placebo and, vitamin-D groups, respectively. IL-6 levels significantly decreased in the vitamin-D vs. placebo group on the 6th day (P = 0.02); however, no significant differences were observed in IL-8 (P = 0.15) and hs-CRP (P = 0.24) levels, mMRC scale (P = 0.45), LOS (P = 0.20), and mortality rates (P = 0.61). Vitamin D replacement as adjunctive therapy may accelerate inflammation resolution in hospitalized AECOPD patients. Further studies were needed to establish vitamin D exact role on inflammation resolution in AECOPD.

Study of the Relationship between ERCC1 Polymorphisms and Response to Platinum-based Chemotherapy in Iranian Patients with Colorectal and Gastric Cancers.

This study was designed to evaluate the effect of excision repair cross complementing group 1 (ERCC1) rs11615 codon 118C/T gene polymorphisms on treatment outcomes in Iranian patients receiving oxaliplatin-based regimens for colorectal (CRC) and gastric cancers (GC). Patients, who were candidates to receive oxaliplatin-based chemotherapy, entered into the study. In 2-week intervals, the patients received combination regimen of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) for 3 months. ERCC1 rs11615 codon 118C/T polymorphism was tested by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method using patients' peripheral blood lymphocytes. The tumor response to chemotherapy was evaluated by examining the size of the tumor using CT scan. Association between response rates, according to the RECIST criteria, and patients' genotypes was evaluated. Any relationship between response rate and possible explanatory factors was also determined. Overall, 40 patients (13 females (32.5%), and 27 males (67.5%)) enrolled in the study. Four patients (10.0%) carried the homo-zygous mutation (T/T genotype), ten patients (25.0%) were heterozygous (C/T genotype), and twenty-six patients (65%) were homo-zygous (C/C genotype). Response rate were 30.77%, 20.00%, and 0.00% for the genotypes C/C, C/T, and T/T, respectively. No significant association between response rate and genotypes was observed (p = 0.64). Patients with well- and moderately-differentiated histological grade of the tumor showed a better response rate (100.00% of 2 patients and 66.66% of 12 patients, respectively) compared to those with poorly differentiated (0.00% of 26 patients) histological grade (p < 0.001). Further multicenter studies are recommended to confirm conclusively our findings.

The Effects of House Cooking Process on Residue Concentrations of 41 Multi-Class Pesticides in Rice.

In current study, the effects of Iranian rice cooking method (Kateh) on residue levels of 41 pesticides were investigated. The pesticides were selected according to Iranian National Standards Organization (INSO) regulations and covered 18 permitted and 23 banned pesticides belonging to different chemical classes such as organophosphate, triazole, and carbamate. A 250 g portion of rice sample was soaked in 2.5 L spiked tap water containing studied pesticides at final concentration 2 µg/mL and then, the effects of washing and cooking were investigated. The pesticides were analyzed simultaneously in a single run using positive electrospray ionisation with multiple reaction monitoring (MRM) after extraction with QuEChERS method. The results showed that washing removed different portions of pesticide residues in the range between 12.0-88.1%. Washing effect was not associated with the water solubility of the pesticides but amount of residue binding to rice matrix was a major factor for residue reduction. In Iranian method of rice preparation, cooking process includes boiling and steam cooking. In this study, the amount of the pesticide residues was decreased in the range of 20.7-100%. Under these conditions, volatilization, hydrolysis, and thermal degradation caused the reduction of the pesticide residues.

Association Between Delayed Graft Function (DGF) Biomarkers and Long-term Outcomes After Living Donor Kidney Transplantation.

BACKGROUND AND OBJECTIVES: The association between preoperative Urine Neutrophil Gelatinase-associated Lipocalin (uNGAL) and interleukin-18 (uIL-18) with poor 1-year allograft function has been shown in deceased-donor kidney transplant recipients previously, and also these markers could predict 3-month allograft function. However, it is unknown whether there is an association between these postoperative biomarkers with important recipient outcomes beyond this time in livedonor transplants. METHODS: NGAL and IL-18 four and 24 hours were measured in live-donor kidney transplant recipients after transplantation. The relationships between changes in these markers with clinical outcomes as well as kidney function were examined at 1 month and 2 years. Moreover, the association between delayed graft function with clinical outcome and Serum Creatinine (SrCr) was evaluated during this period. RESULTS: The Mean age for kidney recipients was 23.9 years. Significant interaction was observed between uNGAL 24 hr (pvalue=0.01) and uIL-18 four and 24 hr after transplantation (pvalue=0.04, 0.03; respectively) with patients' outcome after 1 month and changes in uNGAL with outcomes after 2 years (pvalue= 0.04). CONCLUSION: Changes in urine NGAL postoperative are associated with worst outcomes, 2 years after kidney transplantation, suggesting its potential role in identifying patients that are at high risk for diminished allograft function, outcome and survival.

N-acetylcysteine decreases urinary level of neutrophil gelatinase-associated lipocalin in deceased-donor renal transplant recipients: a randomized clinical trial.

CONTEXT: Acute kidney injury (AKI) is a common complication after kidney transplantation (KT), especially in recipients from deceased donors. Urinary neutrophil gelatinase-associated lipocalin (u-NGAL) is an early and sensitive marker of AKI after transplantation. OBJECTIVES: We assessed the renoprotective effect of N-acetylcysteine (NAC) on u-NGAL levels as an early prognostic marker of graft function immediately after transplantation. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was conducted on 70 deceased-donor KT recipients ( www.irct.ir , trial registration number: IRCT2014090214693N4). Patients received 600 mg oral NAC or placebo twice daily from day 0 to 5 and urine samples were taken before, and on the first and fifth days after transplantation. U-NGAL and early graft function were compared between the two groups. RESULTS: NAC significantly reduced u-NGAL levels compared to placebo (p value = 0.02), while improvement in early graft function with NAC did not reach statistical significance. CONCLUSIONS: This study showed that NAC administration in deceased-donor KT recipients can reduce tubular kidney injury, evidenced by u-NGAL measurements. Improvement in early graft function needs a larger sample size to reach a statistical conclusion.

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.

The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of ventilator associated pneumonia.

PURPOSE: In regard with the effect of immune-stimulants in the treatment of infectious diseases, the effect of vitamin D administration on the outcome of patients with Ventilator-Associated Pneumonia (VAP) with a high rate of mortality, was studied. MATERIAL AND METHOD: In this trial, 46 adult patients suffering from VAP and vitamin D deficiency were enrolled. The first group of patients received single intramuscular injection of vitamin D (300000Unit), while the other group were given the placebo. RESULTS: Administration of vitamin D significantly enhanced its levels (P<0.0001) in the treated patients (12.28±8.26) in comparison with placebo group (1.15±1.50). Serum Interleukin-6 levels were significantly reduced in the treated group compared to placebo (P=0.01). Although C-Reactive protein (CRP) levels showed an improving trend in the vitamin D group, no significant difference between groups (P=0.12) was found. Interestingly, the mortality rate of patients that treated with vitamin D (5/24) was significantly lower (p=0.04) than that of the placebo group (11/22). CONCLUSION: Our results indicate that vitamin D administration can significantly reduce the IL-6 as prognostic marker in VAP patients, and must be considered as adjunct option in the treatment of VAP patients.

Evaluation of Renal Toxicity of Colistin Therapy With Neutrophil Gelatinase-associated Lipocalin: a Biomarker of Renal Tubular Damage.

INTRODUCTION: Nephrotoxicity has been a concern with new dosing regimens of colistin. This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin and the ability of detecting it using neutrophil gelatinase-associated lipocalin (NGAL). MATERIALS AND METHODS: A randomized clinical trial was carried out on 40 patients with multidrug-resistant gram-negative infections assigned into 2 groups to receive high and conventional doses of colistin. Blood samples were taken 4 times for measuring serum NGAL. The incidence of acute kidney injury was also evaluated based on the risk, injury, failure, loss, end-stage renal disease (RIFLE) criteria. RESULTS: Baseline levels of NGAL were not significantly different between the patients on the high dose and conventional dose of colistin. The mean NGAL levels on day 10 were 762.14 ± 415.44 pg/mL and 623.67 ± 272.61 pg/mL, respectively.  However, between-group analysis did not show a significant difference in the NGAL levels. The prevalence of acute kidney injury was 60% and 15% based on the RIFLE criteria, in the high-dose and conventional-dose groups, respectively (P = .003). CONCLUSIONS: Although colistin-induced nephrotoxicity was not confirmed with NGAL levels, our findings, however, showed a higher incidence of acute kidney injury associated with high-dose colistin, defined by the RIFLE criteria. Higher levels of NGAL in the acute kidney injury patients were associated with high-dose regimen of colistin.

Nephrotoxicity of High and Conventional Dosing Regimens of Colistin: A Randomized Clinical Trial.

Nephrotoxicity has been a major long-standing concern about colistin.This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin. A randomized open-labeled clinical trial on 40 patients with multi-drug resistant gram negative infections was designed. Patients were allocated into two equal-size groups receiving high (a loading dose of 9 million international units (MIU) and maintenance doses of 4.5 MIU every 12 h) and conventional dose (2 MIU every 8 h) of colistin. Blood samples were taken on day 1, 3, 5, 7 and 10 of treatment for measuring serum cystatin C (Cys C) levels. Incidence of acute kidney injury (AKI) was also evaluated based on RIFLE criteria. Mean ± sd of the difference between baseline and day 10 Cys C levels in high dose and conventional dose groups were 1.61 ± 0.90 and 1.32 ± 0.48, respectively (P = 0.30). Within group analysis showed increase in Cys C levels in both groups (P = 0.001),however, no significant difference in Cys C levels was seen in between groups analysis (P = 0.13). Prevalence of AKI based on RIFLE criteria was 60% and 15% in high dose and conventional dose groups, respectively (P = 0.003). Comparison of Cys C between AKI (mean ± sd) and non-AKI (mean ± sd) patients, irrespective of colistin dosage regimens, confirmed a significant difference (P < 0.0001). Although, colistin-induced nephrotoxicity, determined by Cys C levels, was not confirmed by our findings, however, higher incidence of AKI in high-dose group, defined by RIFLE criteria, along with higher levels of Cys C in AKI patients are supportive of the higher risk of renal toxicity associated with high-dose regimen of colistin. More RCTs with a larger sample size are recommended.

Evaluating the effect of Matricaria recutita and Mentha piperita herbal mouthwash on management of oral mucositis in patients undergoing hematopoietic stem cell transplantation: A randomized, double blind, placebo controlled clinical trial.

OBJECTIVES: To investigate the effects of Matricaria recutita and Mentha piperita on oral mucositis (OM) in patients undergoing hematopoietic stem cell transplantation (HSCT). DESIGN: Randomized double blind placebo controlled clinical trial. SETTING: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, and Bone Marrow Transplantation Center at Taleghani Teaching Hospital, Tehran, Iran. PARTICIPANTS: Sixty patients undergoing HSCT were randomly assigned to two groups: placebo (n=33), and herbal mouthwash group (n=27). INTERVENTIONS: All patients received the mouthwash one week before HSCT and were instructed to use it three times daily for at least 30s. MAIN OUTCOME MEASURES: OM was graded using National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale (grade 0-5). The Numerical Rating Scale (NRS: 0-10 scale) measured the severity of OM symptoms. RESULTS: The duration, maximum and average daily grade of OM were significantly reduced in the treatment group (P<0.05). The use of herbal mouthwash led to significant improvements in pain intensity (P=0.009), dryness (P=0.04) and dysphagia (P=0.009). Other significant results included: reduced need for complementary medications (P=0.03), narcotic analgesics (P=0.047), total parenteral nutrition (TPN) (P=0.02) and the duration of TPN (P=0.03). CONCLUSION: This study shows that patients receiving the herbal mouthwash experienced less complications and symptoms associated with OM. In summary, it seems that the use of our prepared herbal mouthwash is beneficial for patients undergoing HSCT.