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Background: Status epilepticus (SE) is a series of seizures that can lead to serious neurological damages. Cannabidiol (CBD) is extracted from the cannabis plant, which has been approved as an antiseizure medication. This study aimed to determine the efficacy of various doses of CBD on lithium-pilocarpine-induced SE in rats and possible involvement of multiple pharmacological pathways. We hypothesized that cannabinoid receptors type 1 (CB1) and CB2, as well as GABA A receptors, might have important roles in the anticonvulsant effects of CBD against SE by its anti-inflammatory effects. Methods: SE was induced by intraperitoneal (i.p.) injection of lithium (127 mg/kg, i.p.) and pilocarpine (60 mg/kg, i.p., 20 h after lithium). Forty-two male rats were divided into seven groups (including control and sham groups), and the treated groups received different doses of CBD (1, 3, 5, 10, and 25 mg/kg, i.p.). SE score was recorded over the next 2 h following pilocarpine injection. Then, we measured the levels of pro-inflammatory cytokines, including interleukin (IL)-lβ and tumor necrosis factor (TNF)-α, using ELISA kits. Also we analyzed the expression of CB1, CB2, and GABA A receptors using the Western blot technique. Results: CBD at 5 mg/kg significantly reduced Racine's scale and duration of seizures, and increased the onset time of seizure. Moreover, CBD 5 mg/kg caused significant reductions in the elevated levels of IL-lβ and TNF-α, as well as a significant increase in the decreased level of CB1 receptor expression compared to the control group. In other word, CBD reverted the effects of SE in terms of neuroinflammation and CB1 receptor. Based on the obtained results, CBD was not able to restore the declined levels of CB2 or GABA A receptors. Conclusion: Our study found anticonvulsant effects of CBD on the SE rat model induced by lithium-pilocarpine with probable involvement of CB1 receptors and anti-inflammatory effects by reducing IL-1β and TNF-α markers independent of CB2 and GABA A receptors.

Purpose: The use of natural and herbal products as alternative therapies, in conjunction with blood glucose-lowering medications, is on the rise for patients with diabetes. Our objective was to conduct a systematic review and comprehensive meta-analysis of both human and animal models to investigate the impact of chamomile consumption on glycemic control., Methods: A systematic search was conducted on all published papers from January 1990 up to January 2022 via Scopus, PubMed/Medline, Google Scholar, and ISI Web of Science. Human and animal articles evaluating the effect of chamomile on serum glycemic markers were included. We used the random-effects model to establish the pooled effect size. The dose-dependent effect was also assessed., Results: Overall, 4 clinical trials on human and 8 studies on animals met the inclusion criteria. With regard to RCTs, a favorable effect of chamomile consumption on serum fasting blood glucose (Standardized Mean Differences (SMD): -0.65, 95% CI: -1.00, -0.29, P < 0.001; I 2  = 0%) and hemoglobin A1C (HbA1C) levels (SMD: -0.90, 95% CI: -1.39, -0.40, P < 0.001; I 2  = 45.4%) was observed. Considering animal studies, consumption of chamomile extracts significantly reduced serum blood glucose (SMD: -4.37, 95% CI: -5.76, -2.98, P < 0.001; I 2  = 61.2%). Moreover, each 100 mg/d increase in chamomile extract intervention resulted in a significantly declined blood glucose concentrations (MD: -54.35; 95% CI: -79.77, -28.93, P < 0.001; I 2  = 94.8)., Conclusion: The current meta-analysis revealed that chamomile consumption could exert favorable effects on serum blood glucose and HbA1C. However, additional randomized controlled trials are needed to further confirm these findings., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01345-8., Competing Interests: Conflict of InterestThe authors declare that there is no conflict of interest regarding the publication of this paper., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Introduction: An exaggerated immune response is considered the most important aspect of COVID-19 pathogenesis. Hypertonic saline (HS) has shown promise in combating inflammation in several respiratory diseases. We investigated the effects of nebulized HS on clinical symptoms and inflammatory status in patients with severe novel coronavirus infection (COVID-19) pneumonia., Materials and Methods: We randomly assigned 60 adults admitted to the intensive care unit (ICU) due to severe COVID-19 pneumonia to the experimental (received nebulized 5% saline) and control (received nebulized distilled water) groups. All interventions were applied 4 times daily for 5 days. The levels of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and other clinical factors from venous blood were evaluated before and after intervention application. Mortality rate, intubation rate, and durations of ICU and hospital stay were also compared between groups., Results: The levels of TNF-α (MD: -21.35 [-32.29, -10.40], P  =  0.000) and IL-6 (-9.94 [-18.86, -1.02], P  =  0.003) were lower in the experimental group compared to the control group after applying the interventions. The levels of white blood cell count, PO 2 , and serum sodium were also statistically significant differences between groups. However, we did not observe significant differences in terms of hospitalization durations and mortality rates., Conclusion: Nebulization of HS in patients with severe COVID-19 pneumonia appears to be effective in reducing inflammation, but does not appear to affect intubation rates, mortality, hospitalization, or length of stay in ICU., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background:  In the INSPIRATION-S trial, atorvastatin versus placebo was associated with a nonsignificant 16% reduction in 30-day composite of venous/arterial thrombosis or death in intensive care unit (ICU) patients with COVID-19. Thrombo-inflammatory response in coronavirus disease 2019 (COVID-19) may last beyond the first 30 days., Methods:  This article reports the effects of atorvastatin 20 mg daily versus placebo on 90-day clinical and functional outcomes from INSPIRATION-S, a double-blind multicenter randomized trial of adult ICU patients with COVID-19. The main outcome for this prespecified study was a composite of adjudicated venous/arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause mortality. Functional status was assessed with the Post-COVID-19 Functional Scale., Results:  In the primary analysis, 587 patients were included (age: 57 [Q1-Q3: 45-68] years; 44% women). By 90-day follow-up, the main outcome occurred in 96 (33.1%) patients assigned to atorvastatin and 113 (38.0%) assigned to placebo (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.60-1.05, p  = 0.11). Atorvastatin in patients who presented within 7 days of symptom onset was associated with reduced 90-day hazard for the main outcome (HR: 0.60, 95% CI: 0.42-0.86, p interaction  = 0.02). Atorvastatin use was associated with improved 90-day functional status, although the upper bound CI crossed 1.0 (OR ordinal : 0.64, 95% CI: 0.41-1.01, p  = 0.05)., Conclusion:  Atorvastatin 20 mg compared with placebo did not significantly reduce the 90-day composite of death, treatment with ECMO, or venous/arterial thrombosis. However, the point estimates do not exclude a potential clinically meaningful treatment effect, especially among patients who presented within 7 days of symptom onset (NCT04486508)., Competing Interests: D. V. reports consultant and speaker for BMS/Pfizer, Daiichi-Sankyo, Rovi, and Sanofi. Dr. Gupta received payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook inferior vena cava filter litigation. A. G. holds equity in a health care telecardiology startup, Heartbeat Health, Inc., and received consulting fees from Edwards LifeSciences. M. V. M. has received support from an institutional grant by the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). S. S. S. reports honoraria from Janssen and Chiesi and research grant support from the American Heart Association. G. P. has received research support from Bristol-Myers Squibb/Pfizer Alliance, Bayer, Janssen, Alexion, Amgen, and Boston Scientific Corporation, and consulting fees from Bristol-Myers Squibb/Pfizer Alliance, Boston Scientific Corporation, Janssen, Namsa, Prairie Education and Research Cooperative, Boston Clinical Research Institute, and Amgen. S. A. P. reports being on the Advisory Board for Abbott, Boston Scientific, Medtronic, CSI, Philips, Janssen; research grants: Abbott, Boston Scientific, Surmodics, TriReme Medical, Shockwave Medical; and receiving consulting fees from Terumo and Abiomed. M. M. received an unrestricted educational grant for research from Sanofi, Leo, and Rovi, and fees for participating in advisory meetings from Sanofi. A. J. K. reports institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Amgen, CSI, Philips, ReCor Medical, Neurotronic, Biotronik, Chiesi, Bolt Medical, Magenta Medical, Canon, SoniVie, Shockwave Medical, and Merck. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr. Kirtane controlled the content. Personal: consulting from IMDS; Travel Expenses/Meals from Medtronic, Boston Scientific, Abbott Vascular, CSI, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. S. B. reports unrestricted research grants from Bayer, Concept Medical, INARI, Boston Scientific, Bard, and Sanofi; honoraria from Bayer, Concept Medical, INARI, and Boston Scientific. B. W. V. T. has received research support from Novartis, Swedish Orphan Biovitrum, Olatec Therapeutics, Serpin Pharm, and R-Pharm. He has been a consultant of R-Pharm and Serpin Pharma. G. W. S. has received speaker or other honoraria from Cook, Terumo, and Orchestra Biomed; served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, and Cardiomech; and has received equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. G. Y. H. L. reports consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. H. M. K. reports personal fees from UnitedHealth, personal fees from IBM Watson Health, personal fees from Element Science, personal fees from Aetna, personal fees from Facebook, personal fees from Siegfried & Jensen Law Firm, personal fees from Arnold & Porter Law Firm, personal fees from Ben C. Martin Law Firm, personal fees from National Center for Cardiovascular Diseases, Beijing, ownership of HugoHealth, ownership of Refactor Health, contracts from the Centers for Medicare & Medicaid Services, grants from Medtronic and the Food and Drug Administration, grants from Medtronic and Johnson and Johnson, grants from Shenzhen Center for Health Information, and is a Venture Partner at FPrime. Outside the submitted work. B. B. is supported by a research grant from The Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital. B. B. reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. All other authors report no relevant disclosures., (Thieme. All rights reserved.)

Background: Pulmonary physiotherapy (PPT) is an important treatment in the management of patients with different types of pulmonary disorders. We aimed to evaluate safety and efficacy of PPT in hospitalized patients with severe COVID-19 pneumonia., Methods: In this randomised, single-blind, controlled trial, we enrolled hospitalized, non-intubated patients (18 to 75 years with oxygen saturation (Spo2) in free-air breathing ≤90%) with COVID-19 pneumonia at a referral hospital. Participants were randomly assigned (1:1) to receive PPT (six sessions PPT with breathing exercises and airway clearance techniques) or basic care. The primary outcomes were venous blood O2 (pO2) and CO2 (pCO2) pressures, Spo2, and three-minute walking test (3MWT) that were assessed before and end of sixth session. Secondary outcomes included level of dyspnea, venous blood PH, one-month mortality, three-month mortality and short form-36 (SF-36) after one and three months. The assessor was blinded to the assignment. This trial is registered with ClinicalTrials.gov (NCT04357340)., Findings: In April-May 2020, 40 participants were randomly assigned to PPT or basic care groups. While at the end of intervention, pO2 (adjusted mean difference to baseline measure (AMD) 6.43 mmHg [95%CI 2.8, 10.07], P<0.01), Spo2 (AMD 4.43% [95%CI 2.04, 6.83], P = 0.0011), and 3MTW (AMD 91.44 m [95%CI 68.88, 113.99], P<0.01) were higher in PPT group and basic care group, pCO2 was not improved (AMD -2.1 mmHg [95%CI-6.36, 2.21], P = 0.33). Based on the logistic model adjusted to baseline Spo2, the risks of mortality were reduced 81% ([95%CI: 97% reduction to 30% increase], P = .09) and 84% ([95%CI 74% reduction to 5% increase], P = .06) at one-month and three-month, respectively. There were no significant differences in most SF-36 domains scores after one and three months. No serious adverse event was observed during PPT sessions., Conclusion: Early PPT can be considered a safe and relatively effective therapeutic choice for patients with severe COVID-19., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Javaherian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The goal of this study was to identify biomarker(s) to assign risk of mortality in COVID-19 patients to improve intensive care unit (ICU) and coronary care unit  management. A total of 100 confirmed COVID-19 patients admitted at Imam Khomeini Hospital in Tehran, were compared to 70 control subjects. Peripheral blood leukocyte was studied using staining reagents included CD3, CD4, CD8, HLA-DR, CD19, CD16, and CD56. The immunophenotyping analysis was evaluated using the FACSCalibur instrument. To investigate the cell density of lung infiltrating T cells, postmortem slides of needle necropsies taken from the lung tissue of 3 critical patients were evaluated by immunohistochemistry staining. The number of lymphocyte subpopulations was significantly lower in COVID-19 patients than in the control group. Regarding the disease severity, the absolute count of T, NK, and HLA-DR+ T cells were significantly reduced in severe patients compared to the moderate ones. The critical patients had a significantly lower count of CD8-HLA-DR+ T cells than the moderate cases. Regarding the disease mortality, based on univariate analysis, the count of HLA-DR+ T, CD8- HLA-DR+ T, and CD8+ HLA-DR+ T cells was associated with mortality in COVID-19 patients. Receiver operating characteristic curve analysis showed the count of CD8+ HLA-DR+ T cells is the best candidate as a biomarker for mortality outcome. Furthermore, pulmonary infiltration of T cells in the lung tissue showed only slight infiltrations of CD3+ T cells, with an equal percentage of CD4+ and CD8+ T cell subpopulation in the lung tissue. These findings suggest that close monitoring of the value of CD8+ HLA-DR+ T cells in COVID-19 patients may be helpful to identify high-risk patients. However, further studies with larger sample size are needed., (© 2022 Wiley Periodicals LLC.)

Background: Improvement of predictive tools for recognition of airway edema is crucial for safe extubation and patient safety. This study aimed to evaluate the diagnostic accuracy of the Gargle test (GT) as a new test for assessing airway edema and predicting successful extubation in patients admitted to the intensive care unit (ICU)., Method: In this prospective observational study, patients underwent head and neck surgeries and admitted to ICU included. All the patients were weaned based on the same protocol.Quantitative Cuff Leak Test (CLT) and qualitative CLTwere first applied followed by GT with normal saline 0.9%. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated., Results: One hundred and eighteen (male 67, female 51) participated in this study. The agreement between GT and CLT was low (Kappa: quantitative CLT 0.07, qualitative CLT 0.21). The GT compared to CLT had higher sensitivity (33.3% vs 16.6%), specificity (96.3% vs qualitative CLT 92.8%, quantitative CLT 79.4%), PPV (33.3% vs qualitative CLT 11.11%, quantitative CLT 4.0%), NPV (96.3% vs qualitative CLT 95.4%, quantitative CLT 94.6%), and accuracy (92.92% vs qualitative CLT 88.98%, quantitative CLT 76.27%. The cut-off value for GT was estimated 16.5% (sensitivity 74.1% and specificity 60%)., Conclusion: The GT is a simple accurate test and can be used as a new test in the ICU for recognition of airway edema and prediction of safe extubation in patients with head and neck surgeries., Competing Interests: None authors are to be declared., (© 2022 The Authors.)

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is the most dangerous form of the coronavirus, which causes COVID-19. In patients with severe COVID-19, the immune system becomes markedly overactive. There is evidence that supplementation with select micronutrients may play a role in maintaining immune system function in this patient population. Throughout the COVID-19 pandemic, significant emphasis has been placed on the importance of supplementing critical micronutrients such as Vitamin C and Zinc (Zn) due to their immunomodulatory effects. Viral infections, like COVID-19, increase physiological demand for these micronutrients. Therefore, the purpose of this review was to provide comprehensive information regarding the potential effectiveness of Vitamin C and Zn supplementation during viral infection and specifically COVID-19. This review demonstrated a relation between Vitamin C and Zn deficiency and a reduction in the innate immune response, which can ultimately make patients with COVID-19 more vulnerable to viral infection. As such, adequate intake of Vitamin C and Zn, as an adjunctive therapeutic approach with any necessary pharmacological treatment(s), may be necessary to mitigate the adverse physiological effects of COVID-19. To truly clarify the role of Vitamin C and Zn supplementation in the management of COVID-19, we must wait for the results of ongoing randomized controlled trials. The toxicity of Vitamin C and Zn should also be considered to prevent over-supplementation. Over-supplementation of Vitamin C can lead to oxalate toxicity, while increased Zn intake can reduce immune system function. In summary, Vitamin C and Zn supplementation may be useful in mitigating COVID-19 symptomology., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 The Authors.)

Background: The Lumbar Spine Instability Questionnaire (LSIQ) is a self-reported measure of clinical instability of the lumbar spine. This study aimed to translate and culturally adapt the LSIQ into Persian language (LSIQ-P) and to evaluate its reliability and validity in a sample of patients with chronic non-specific low back pain (LBP)., Methods: In a cross-sectional study, the LSIQ was translated using guidelines. Participants with chronic non-specific LBP, aged ≥ 18 years old, answered an online survey consisting of LSIQ-P, the Persian Functional Rating Index (FRI), and the pain Numeric Rating Scale (NRS). Construct validity, internal consistency reliability, test-retest reliability, standard error of measurement (SEM), smallest detectable change (SDC), discriminant validity, and factor analysis were evaluated., Results: The LSIQ was successfully adapted into Persian. A sample of 100 participants with LBP and 100 healthy subjects completed the survey. Floor and ceiling effects were not observed. Cronbach's alpha = 0.767 and ICC agreement  = 0.78 indicated good internal consistency and test-retest reliability. The SEM and SDC were 1.53 and 4.24, respectively. Construct validity of LSIQ-P was confirmed with significant correlation with Persian FRI (r = 0.44, p < 0.001) and pain NRS (r = 0.30, p = 0.003). An evidence of discriminant validity was demonstrated by significant difference in LSIQ-P total scores between the patients with LBP and healthy subjects, and between the patients with high total score ≥ 9 and those with low total score < 9 on the LSIQ-P. The LSIQ-P was found a multidimensional instrument with eight items appeared being redundant., Conclusions: The Persian LSIQ showed satisfactory metric characteristics of reliability and validity. Further studies are required to elucidate the internal structure of the LSIQ-P., (© 2022. The Author(s).)

Background: COVID-19 pandemic has become a global dilemma since December 2019. Are the standard scores, such as acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) score, accurate for predicting the mortality rate of COVID-19 or the need for new scores? We aimed to evaluate the mortality predictive value of APACHE II and SOFA scores in critically ill COVID-19 patients., Methods: In a cohort study, we enrolled 204 confirmed COVID-19 patients admitted to the intensive care units at the Imam Khomeini hospital complex. APACHE II on the first day and daily SOFA scoring were performed. The primary outcome was the mortality rate in the nonsurvived and survived groups, and the secondary outcome was organ dysfunction. Two groups of survived and nonsurvived patients were compared by the chi-square test for categorical variables and an independent sample t -test for continuous variables. We used logistic regression models to estimate the mortality risk of high APACHE II and SOFA scores., Result: Among 204 severe COVID-19 patients, 114 patients (55.9%) expired and 169 patients (82.8%) had at least one comorbidity that 103 (60.9%) of them did not survive ( P =0.002). Invasive mechanical ventilation and its duration were significantly different between survived and nonsurvived groups ( P ≤ 0.001 and P =0.002, respectively). Mean APACHE II and mean SOFA scores were significantly higher in the nonsurvived than in the survived group (14.4 ± 5.7 vs. 9.5 ± 5.1, P ≤ 0.001, 7.3 ± 3.1 vs. 3.1 ± 1.1, P ≤ 0.001, respectively). The area under the curve was 89.5% for SOFA and 73% for the APACHE II score. Respiratory diseases and malignancy were risk factors for the mortality rate ( P =0.004 and P =0.007, respectively) against diabetes and hypertension., Conclusion: The daily SOFA was a better mortality predictor than the APACHE II in critically ill COVID-19 patients. But they could not predict death with high accuracy. We need new scoring with consideration of the prognostic factors and daily evaluation of changes in clinical conditions., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Mohammad Taghi Beigmohammadi et al.)

Introduction: The introduction of a self-collection sampling method with less discomfort would be of great benefit in reducing the risk of medical provider's contamination and patient's acceptance. The aim of the present study was to investigate saliva samples' diagnostic performance for the COVID-19 RT-PCR test compared to pharyngeal swabs., Methodology: From individuals referred to a medical center with presentations compatible with COVID-19 who were eligible for molecular diagnostic tests, 80 cases were selected. Nasopharyngeal and oropharyngeal swabs (placed into the same transport tube) along with self-collected saliva sample were taken from each participant for COVID-19 RT-PCR assay. The results of pharyngeal swabs and saliva sample were compared., Results: Sixty-two (78%) infected cases were detected, of whom 31 (39%) cases tested positive for both pharyngeal swab and saliva samples. 24 (30%) and 7 (9%) cases tested positive only for pharyngeal or saliva samples, respectively. The overall percentage of agreement between pharyngeal swab and saliva sample was 61%, with a kappa value of 0.24 (p-value = 0.019, 95% CI: 0.04-0.44), showing a fair level of agreement. The diagnostic sensitivity of pharyngeal swabs was 88.71% (95% CI: 78.11-95.34), and the diagnostic sensitivity of saliva samples was 61.29% (95% CI: 48.07-73.40). Compared to pharyngeal swabs (oropharyngeal and nasopharyngeal swabs in the same collection tube), an important observation was that seven more positive cases were detected among saliva samples., Conclusions: The findings of the present study indicated that self-collected saliva samples cannot replace pharyngeal swabs. Still, saliva samples significantly increased the case detection rate and can be used along with pharyngeal swabs., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Alireza Abdollahi, Samaneh Salarvand, Reza Ghalehtaki, Bita Jafarzadeh, Mohammad Taghi Beigmohammadi, Fereshteh Ghiasvand, Abbas Shakoori, Hoda Khoshnevis, Mohammad Arabzadeh, Saeed Nateghi, Vahid Mehrtash.)

Background and Objective: The present study aimed to investigate the effects of propolis and melatonin supplementation on inflammation, clinical outcomes, and oxidative stress markers in patients with primary pneumosepsis., Materials and Methods: This pilot randomized controlled trial was conducted on 55 patients with primary pneumosepsis who were randomly assigned to the intervention and control groups. In the three intervention groups, the patients received propolis alone (1,000 mg/day), propolis (1,000 mg/day) plus melatonin (20 mg/day), and melatonin alone (20 mg/day). The control group received placebo. The inflammatory and oxidative stress markers as well as clinical outcomes were evaluated before and after the intervention, and the 28-day survival rate was also recorded., Results: After the intervention, the combination of propolis and melatonin significantly reduced interleukin-6 (-55.282 pg/mL) and C-reactive protein (-21.656 mg/L) levels, while increasing gavage intake (326.680 mL/day) and improving some clinical outcomes (APACHE II, SOFA, and NUTRIC scores) compared to the control group. However, no significant difference was observed between the groups in terms of oxidative stress and hematological indices. In addition, there was no significant difference in the 28-day survival rate between the groups (p = 0.07)., Conclusion: Supplementation with propolis and melatonin may improve clinical outcomes by reducing inflammation. Further investigations are required to confirm these findings., (© 2022 S. Karger AG, Basel.)

Background: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown., Methods: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding., Results: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p  = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24)., Conclusion: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up., Competing Interests: Dr. Parikh reports being on the Advisory Board for Abbott, Boston Scientific, Medtronic, CSI, Philips, Janssen; research grants: Abbott, Boston Scientific, Surmodics, TriReme Medical, Shockwave Medical; and receiving consulting fees from Terumo and Abiomed. Dr. Gupta received payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook inferior vena cava filter litigation. Dr. Gupta holds equity in a health care telecardiology startup, Heartbeat Health, Inc. and received consulting fees from Edwards LifeSciences. Dr. Madhavan has received support from an institutional grant by the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr. Sethi reports honoraria from Janssen and Chiesi and research grant support from the American Heart Association. Dr. Piazza has received research grant support to Brigham and Women's Hospital from EKOS, a BTG International Group company, Bayer, the Bristol Myers Squibb/Pfizer Alliance, Portola, and Janssen. He has received consulting fees from Amgen, Pfizer, Boston Scientific Corporation, and Thrombolex. Dr. Kirtane reports institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical. In addition to research grants, institutional funding includes fees paid to Columbia University and/or Cardiovascular Research Foundation for speaking engagements and/or consulting. Personal: travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr. Van Tassell received research support from Novartis, Swedish Orphan Biovitrum, Olatec Therapeutics, and Serpin Pharma. He is a consultant of R-Pharm, Serpin Pharma. Dr. Stone has received speaker or other honoraria from Cook, Terumo, and Orchestra Biomed; served as a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech; and has received equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, MedFocus family of funds, and Valfix. Dr. Lip reports consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. Dr. Krumholz reports personal fees from UnitedHealth, personal fees from IBM Watson Health, personal fees from Element Science, personal fees from Aetna, personal fees from Facebook, personal fees from Siegfried & Jensen Law Firm, personal fees from Arnold & Porter Law Firm, personal fees from Ben C. Martin Law Firm, personal fees from National Center for Cardiovascular Diseases, Beijing, ownership of HugoHealth, ownership of Refactor Health, contracts from the Centers for Medicare & Medicaid Services, grants from Medtronic and the Food and Drug Administration, grants from Medtronic and Johnson and Johnson, grants from Shenzhen Center for Health Information, and is a Venture Partner at FPrime, outside the submitted work. Dr. Bikdeli reports that he is a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of IVC filters. All other authors report no relevant Enoxaparin was provided through Alborz Darou, Pooyesh Darou, and Caspian Pharmaceuticals companies, and atorvastatin and matching placebo were provided by Sobhan Darou. None of these companies were study sponsors and they had no other role and will not have a role in the design, conduct, analysis, or interpretation of the ongoing results or the decision to submit the resultant manuscript(s)., (Thieme. All rights reserved.)

Background and Objective: Because of the effect of vitamins on modulating the immune system function, we have evaluated the effect of supplementation with vitamins A, B, C, D, and E in ICU-admitted patients with COVID-19., Methods: This study was a randomized and single-blinded clinical trial in which 60 subjects were randomly assigned to two groups. The intervention group (n=30) received vitamins, and the control group did not receive any vitamin or placebo. The intervention was included 25,000 IU daily of vitamins A, 600,000 IU once during the study of D, 300 IU twice daily of E, 500 mg four times daily of C, and one amp daily of B complex for 7 days. At baseline and after the 7-day intervention, the serum levels of inflammatory markers, vitamins, and the SOFA score were assessed. In addition, the mortality rate and duration of hospitalization were evaluated after the intervention (IRCT registration number: IRCT20200319046819N1/registration date: 2020-04-04, https://www.irct.ir/trial/46838 )., Results: Significant changes were detected in serum levels of vitamins (p < 0.001 for all vitamins), ESR (p < 0.001), CRP (p = 0.001), IL6 (p = 0.003), TNF-a (p = 0.001), and SOFA score (p < 0.001) after intervention compared with the control group. The effect of vitamins on the mortality rate was not statistically significant (p=0.112). The prolonged hospitalization rate to more than 7 days was significantly lower in the intervention group than the control group (p=0.001). Regarding the effect size, there was a significant and inverse association between receiving the intervention and prolonged hospitalization (OR = 0.135, 95% CI 0.038-0.481; p=0.002); however, after adjusting for confounders, it was not significant (OR=0.402, 95% CI 0.086-1.883; p=0.247)., Conclusion: Supplementation with vitamins A, B, C, D, and E could improve the inflammatory response and decrease the severity of disease in ICU-admitted patients with COVID-19., (© 2021. The Author(s).)

Objectives: This study aimed to compare the serum level of micronutrients with normal amounts, and assess their association with the severity of disease and inflammatory cytokines in patients with coronavirus disease 2019 (COVID-19)., Methods: The present cross-sectional study included 60 patients admitted to the intensive care unit with COVID-19. We recorded data on demographic characteristics, anthropometric information, and medical history. Serum levels of inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma, tumor necrosis factor-alpha, interleukin-6), vitamins (A, B 9 , B 12 , C, D, E), and minerals (magnesium, zinc, iron) were measured. A radiologist assessed the severity of lung involvement according to patient computed tomography scans. The severity of illness was evaluated with the Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) score, oxygen saturation, and body temperature. Independent associations among the serum levels of micronutrients with the severity of COVID-19 were measured., Results: Median patient age was 53.50 years (interquartile range, 12.75 years). Except for vitamin A and zinc, serum levels of other micronutrients were lower than the minimum normal. Patients with APACHE score ≥25 had a higher body mass index (P = 0.044), body temperature (P = 0.003), erythrocyte sedimentation rate (P = 0.008), C-reactive protein (P = 0.003), and lower oxygen saturation (P = 0.005), serum levels of vitamin D (P = < 0.001), and zinc (P = < 0.001) compared with patients with APACHE score <25. We found that lower serum levels of vitamin D, magnesium, and zinc were significantly and independently associated with higher APACHE scores (P = 0.001, 0.028, and < 0.001, respectively) and higher lung involvement (P = 0.002, 0.045, and < 0.001, respectively)., Conclusions: Lower serum levels of vitamin D, zinc, and magnesium were involved in severe COVID-19., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis., Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU)., Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020., Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up., Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated., Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01)., Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19., Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.

Background . A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been affecting almost all nations around the world. Most infected patients who have been admitted to intensive care units show SARS signs. In this study, we aimed to achieve a better understanding of pathological alterations that take place during the novel coronavirus infection in most presumed affected organs. Methods . We performed postmortem core needle biopsies from lung, heart, and liver on 7 deceased patients who had died of coronavirus disease 2019. Prepared tissue sections were observed by 2 expert pathologists. Results . Diffuse alveolar damage was the main pathologic finding in the lung tissue samples. Patients with hospitalization durations of more than 10 days showed evidence of organization. Multinucleated cells in alveolar spaces and alveolar walls, atypical enlarged cells, accumulation of macrophages in alveolar spaces, and congestion of vascular channels were the other histopathologic alteration of the lung. None of our heart biopsy samples met the criteria for myocarditis. Liver biopsies showed congestion, micro- and macro-vesicular changes, and minimal to mild portal inflammation, in the majority of cases. Conclusions . Similar to the previous coronavirus infection in 2003, the main pathologic finding in the lung was diffuse alveolar damage with a pattern of organization in prolonged cases. The SARS-CoV-2 infection does not cause myocarditis, and the ischemia of myocardium is the most probable justification of the observed pathologic changes in the heart. Liver tissue sections mostly showed nonspecific findings; however, ischemia of the liver can be identified in some cases.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Background & Aims: Critically ill patients are provided with the intensive care medicine to prevent further complications, including malnutrition, disease progression, and even death. This study was intended to assess nutritional support and its' efficacy in the Intensive Care Units (ICUs) of Iran., Methods: This cross-sectional study assessed 50 ICU's patients out of 25 hospitals in the 10 major regions of Iran's health system and was performed using the multistage cluster sampling design. The data were collected from patient's medical records, ICU nursing sheets, patients or their relatives from 2017 to 2018. Nutritional status was investigated by modified NUTRIC score and food frequency checklist., Results: This study included 1321 ICU patients with the mean age of 54.8 ± 19.97 years, mean mNUTRIC score of 3.4 ± 2.14, and malnutrition rate of 32.6%. The mean time of first feeding was the second day and most of patients (66%) received nutrition support, mainly through enteral (57.2%) or oral (37%) route during ICU stay. The patients received 59.2 ± 37.78 percent of required calorie and 55.5 ± 30.04 percent of required protein. Adequate intake of energy and protein was provided for 16.2% and 10.7% of the patients, respectively. The result of regression analysis showed that the odds ratio of mNUTRIC score was 0.85 (95% confidence interval [CI] = 0.74-0.98) and APACHE II was 0.92 (95%CI = 0.89-0.95) for the prediction of energy deficiency. Nutrition intake was significantly different from patient's nutritional requirements both in terms of energy (p < 0.001) and protein (p < 0.001). Also, mean mNUTRIC score varied notably (p = 0.011) with changing in energy intake, defined as underfeeding, adequate feeding, and overfeeding., Conclusion: The present findings shown that, provided nutritional care for ICU patients is not adequate for their requirements and nutritional status., Competing Interests: Conflicts of interest None declared., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown., Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts., Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: We studied the clinical characteristics and outcomes of 905 hospitalized coronavirus disease 2019 (COVID-19) patients admitted to Imam Khomeini Hospital Complex (IKHC), Tehran, Iran., Methods: COVID-19 patients were recruited based on clinical symptoms and patterns of computed tomography (CT) imaging between February 20 and March 19. All patients were tested for the presence of COVID-19 RNA. The Poisson regression model estimated the incidence rate ratio (IRR) for different parameters., Results: The average age (± standard deviation) was 56.9 (±15.7) years and 61.77% were male. The most common symptoms were fever (93.59%), dry cough (79.78%), and dyspnea (75.69%). Only 43.76% of patients were positive for the RT-PCR COVID-19 test. Prevalence of lymphopenia was 42.9% and more than 90% had elevated lactate dehydrogenase (LDH) or C-reactive protein (CRP). About 11% were severe cases, and 13.7% died in the hospital. The median length of stay (LOS) was 3 days. We found higher risks of mortality in patients who were older than 70 years (IRR = 11.77, 95% CI 3.63-38.18), underwent mechanical ventilation (IRR = 7.36, 95% CI 5.06-10.7), were admitted to the intensive care unit (ICU) (IRR = 5.47, 95% CI 4.00-8.38), tested positive on the COVID-19 test (IRR = 2.80, 95% CI 1.64-3.55), and reported a history of comorbidity (IRR = 1.76, 95% CI 1.07-2.89) compared to their corresponding reference groups. Hydroxychloroquine therapy was not associated with mortality in our study., Conclusion: Older age, experiencing a severe form of the disease, and having a comorbidity were the most important prognostic factors for COVID-19 infection. Larger studies are needed to perform further subgroup analyses and verify high-risk groups., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Objectives: This study will evaluate the main hypothesis that supplementation with vitamins A, B, C, D, and E significantly improves the severity and mortality rate in ICU patients with COVID-19., Trial Design: This study is a randomized, single-blinded, two-arm (1:1 ratio) parallel group clinical trial., Participants: We are conducting this study in patients with COVID-19 admitted to intensive care units at the Imam Khomeini Hospital Complex in Tehran, Iran. The inclusion criteria are as follows: (1) aged between 20 and 60 years, (2) both male and female patients with COVID-19, (3) clinical or definitive diagnosis (using polymerase chain reaction (PCR) test), (4) patients have not participated in other clinical trials, and (5) no renal or hepatic abnormalities. The exclusion criteria are as follows: (1) patients with specific and rare viral diseases such as HIV and (2) patients who have been undergoing chemotherapy for the past month., Intervention and Comparator: Duration of intervention: 7 days from randomization Intervention in the treatment group: Vitamin A 25,000 IU daily Vitamin D 600,000 IU once during study Vitamin E 300 IU twice daily Vitamin C is taken four times per day B vitamins are taken as a daily Soluvit [which included thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B 2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B 6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg] The control group will not receive any supplements or placebo. All supplements are made in Iran except for Soluvit (from Fresenius Kabi, New Zealand)., Main Outcomes: 1. Weight, height, and BMI 2. Severity of pulmonary involvement according to CT scan 3. Respiratory support (invasive or non-invasive) 4. Percentage of oxygen saturation (SpO2 level) 5. Serum levels of WBC, CRP, ESR, IL6, IFN-G, and TNF-α 6. The patient's body temperature 7. The presence or absence of involvement of organs other than the lungs (e.g., heart, liver, kidneys) 8. Duration of hospitalization 9. Mortality rate RANDOMIZATION: At baseline, eligible patients were randomly assigned to a 1:1 ratio to one of two groups: intervention and control. Block randomization is used based on the gender of patients., Blinding (masking): Patients are unaware of being placed in the intervention or control groups after signing consent. All treatment staff will be aware of which group each of the patients is in due to the specific conditions of the ICU and the absence of placebo for the control group., Numbers to Be Randomized (sample Size): The researchers plan to include 60 patients in total, with 30 patients in each group., Trial Status: This is the first version of the protocol which started on April 2, 2020. Recruitment began April 2, 2020, and is expected to be complete by July 4, 2020., Trial Registration: The Iranian Registry of Clinical Trials IRCT20200319046819N1 . Registered on April 4, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol (Fig. 1, Table 1).

Objectives: There is currently no evidence that whether magnesium supplementation would improve stress-induced hyperglycemia (SIH) in critically ill patients. In this study, effects of magnesium loading dose on insulin resistance (IR) indices were evaluated in critically ill patients without diabetes having SIH., Methods: Seventy critically ill patients with SIH were assigned to receive a loading dose of magnesium (7.5 g of magnesium sulfate in 500 mL normal saline as intravenous infusion over an 8-hour period) or placebo. Changes in baseline of serum and intracellular magnesium and serum adiponectin (AD) levels, homeostasis model assessment of IR (HOMA-IR), and HOMA-AD ratio were assessed in this study., Results: Serum and intracellular magnesium levels increased significantly in patients in the magnesium group ( P < .001). At day 3, there were significant differences between the magnesium group and the placebo group in the mean changes from baseline in the HOMA (between-group difference: -0.11; 95% confidence interval [CI]: -0.19 to -0.01; P = .02), the AD (between-group difference: 0.94; 95% CI: 0.41-1.48; P = .04), and the HOMA-AD ratio (between-group difference: -0.03; 95% CI: -0.04 to -0.01; P < .001)., Conclusion: In the present study, a single-loading dose of intravenous magnesium improved IR indices in critically ill patients with SIH.

Introduction: Ventilator-associated pneumonia (VAP) has been considered as a healthcare-associated infection with high mortality. Acinetobacter baumannii and Klebsiella pneumoniae are the common causes of VAPs around the world., Methodology: This research was a retrospective observational study in the intensive care unit (ICU) in a tertiary referral collegiate hospital in Tehran between March 2016 and May 2018. Patients who fulfilled VAP due to documented Multidrug Resistant Acinetobacter baumannii (MDR-AB) or Extended Spectrum Beta Lactamase-producing Klebsiella pneumoniae (ESBL-KP) criteria were enrolled. General demographic features, duration of hospital stay, antimicrobial treatment regimens, duration of ICU admission, the period of mechanical ventilation (MV) and 30-day mortality were documented and compared., Results: 210 patients were found with clinical, microbiological and radiological evidence of VAP. In total, 76 patients with MDR-AB and 76 patients with ESBL-KP infections were matched in the final analysis. Duration of hospitalization in the patients with MDR-AB was significantly more than that of patients infected with ESBL-KP (p-value: 0.045). Patients diagnosed with MDR-AB VAP had a 65.8% mortality rate compared to 42.1% in the ESBL-KP infection group (p = 0.003)., Conclusions: Results of the present study demonstrated that VAPs caused by MDR-AB may be more hazardous than ESBL-KP VAPs because they could be accompanied by a longer hospitalization course and even a higher mortality., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Mohammadreza Salehi, Sirous Jafari, Lida Ghafouri, Hossein Malekafzali Ardakani, Alireza Abdollahi, Mohammad Taghi Beigmohammadi, Seyed Ali Dehghan Manshadi, Mohammad Mehdi Feizabadi, Masoud Ramezani, Hamidreza Abtahi, Arash Seifi.)

Introduction and Aim: Malnutrition is a complication of hospitalization in critically ill patients. This event is occurred because of disease and therapeutic processes for curing the patients. Determination of nutritional status helps physicians and clinical nutritionists decide on the best regimen which should be prescribed for a patient. In the current study, we aimed to report the nutritional status ofpatientshospitalizedin the intensive care unit (ICU)., Method of Study: We used three standard tolls, including Subjective global assessment (SGA), Nutrition Risk in the Critically Ill (NUTRIC) Score and nutrition risk screening (NRS) questionnaires via a multi-stage sampling for different ICU wards of 32 university hospitals in Iran. Frequencies and rates of nutritional scores, comparative studies, and determined agreement of scoring systems and nutritional status in any ward of hospitals were evaluated., Results: There were 771 males and 540 female Cancer and trauma patients had the best and worst nutritional scores, respectively. Using NRS and NUTRIC, the low-risk scores were more frequent than thehigh-riskscores among ICU patients. SGA showed that most patients were in grades A (well nutritional status) or B (moderate nutritional status), andfew caseswere in grade C (poor nutritional status).The high-risk nutritional score wasobtained for older patients. NUTRIC and NRS had better agreement for diagnosis and differentiation of malnutrition than NUTRIC-SGA or NRS-SGA pairs. However, there was no strong agreement between the mentioned pairs., Conclusion: Nutritional status of patients hospitalized in ICU wards in Iran wassomewhat better than other countries that this could be due to the highly observed guidelines of patient's care in Iran. Anyway,it is suggested that a more precise tool of nutritional scoresto be validated for patients hospitalized in ICU·In addition, better medical care needs a well evaluation of nutritional insufficiencies and what is necessary for compensation using complementary regimens., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Aim: Efficacy of colistin and ampicillin-sulbactam have not been compared in treatment of ventilator-associated pneumonia due to A. baumannii. Efficacy of colistin and ampicillin-sulbactam in combination with meropenem were compared in treatment of ventilator-associated pneumonia due to carbapenem-resistant A. baumannii., Method: 47 patients with ventilator-associated pneumonia due to carbapenem-resistant A. baumannii were randomized to receive meropenem/colistin or meropenem/ampicillin-sulbactam for 14 days. Clinical and microbiological responses and 28-day mortality were considered as outcomes., Results: Clinical response (75 vs 69.6%; p = 0.75) and microbial eradication (87.50 vs 91.3%; p = 0.59) were comparable between meropenem/colistin and meropenem/ampicillin-sulbactam groups, respectively., Conclusion: In this study, clinical and microbiological response were comparable between the meropenem/colistin and meropenem/ampicillin-sulbactam groups.

Objective: To evaluate the effectiveness of topical pentoxifylline (PTX) on pressure ulcer (PU) healing in critically ill patients., Method: In this randomised, double blind, placebo-controlled clinical trial, patients with category I or II PUs were randomly assigned to receive either topical PTX 5% or a placebo twice daily for 14 days. Changes in PU characteristics (category and size) were assessed. The category of the PU was determined by the Stirling Pressure Ulcer Severity Scale (two-digit) at baseline (day zero), day seven and day 14 of treatment. PU length and width was measured with a disposable ruler and expressed as cm 2 ., Results: A total of 112 adult patients were enrolled in the study. Median PU size and score at day zero were 32 (10.00-69.33)cm 2 and 1(1.00-2.00) respectively. In the PTX group, the mean differences (95% confidence interval, CI) of all PU scores and sizes decreased significantly across the intervals (day seven versus day zero, day 14 versus day zero, and day 14 versus day seven), compared with the placebo group Conclusion: The severity and size of PUs improved significantly in patients who received topical PTX 5% ointment twice a day for 14 days compared with those in the placebo group. Topical PTX may be considered as a potential option in the treatment of categories I and II PUs in critically ill patients.

Aim: Adequacy of enteral nutrition (EN) alone as stress ulcer prophylaxis (SUP) is controversial. The aim of this study was to compare efficacy of EN alone and ranitidine plus EN as SUP., Method: Critically ill adults with indications to receive SUP were randomized to ranitidine 50 mg IV every 8 h plus EN (SUP) or EN alone (non-SUP) group for 7 days. Besides, endoscopy was performed at the time of recruitment and on day 7., Results: During the study period, only one patient in each group of SUP and non-SUP experienced gastrointestinal bleeding. At the time of recruitment, gastric erosion and erythema were the most endoscopic findings in the SUP and non-SUP groups. These findings did not significantly change at the end of the study (p = 0.21)., Conclusion: EN was at least effective as ranitidine plus EN as SUP.

Introduction: Most of the patients hospitalized in the emergency department (ED) are in need of transfer to other hospital wards or paraclinic units. This process is called intrahospital transfer (IHT) that may lead to a wide range of complications known as unexpected events (UE)., Objective: In the present study we decided to evaluate the effect of using a pre-designed protocol on decrease of UEs and safety improvement of IHT among patients hospitalized in ED., Method: The present cross-sectional study was carried out in 2016 in the ED of Imam Khomeini Hospital, Tehran, Iran. All patients with triage levels of 1 and 2 who were in need of temporary or permanent transfer to other departments of the studied treatment center based on clinical indication as decided by the in-charge physician were enrolled in the study. This study was conducted in 3 phases of pre-intervention, intervention and post-intervention. Any UE was recorded in first phase. During intervention phase ED-IHT protocol was prepared and implemented. the checklist of complications and UEs during transfer was filled again and pre- and post-intervention results were compared., Results: In this study, 207 patients with the mean age of 58.9 ± 20.6 years were evaluated (61.4% male). Demographic data and baseline characteristics of the studied patients in the phases before and after implementation of the protocol has no significant difference. Overall, before implementation of the protocol out of the 105 studied patients, a total of 35 patients (33.3%) were affected by UE during transfer, but after implementation of the protocol this rate decreased to 11 patients (10.8%) out of the 103 studied patients and this decrease was statistically significant (p < 0.001)., Conclusion: Based on the results obtained from this study, it seems that performing the IHT protocol specialized for ED patients has been effective in decreasing UE cases.

Background: The most common clinical indication of aminoglycosides (AG) is the treatment of serious Gram-negative infections. The aim of this study was to evaluate plausible effects of atorvastatin on the biomarkers of acute kidney injury (AKI) in patients receiving amikacin., Materials and Methods: In this double-blinded randomized clinical trial, fifty patients (25 in each group) receiving amikacin (15 mg/kg/day) were randomly assigned to either atorvastatin (40 mg/day) or placebo (40 mg/day) groups for 7 days. Blood urea nitrogen (BUN), serum creatinine (SCr), and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels were measured at days 0, 1, and 7 of amikacin treatment., Results: During the study period, 4 (8%) patients including two patients in each atorvastatin and placebo group experienced AKI. Urine NGAL/urine Cr did not change significantly between and within placebo and atorvastatin groups during the study period. Similarly, the mean changes in SCr, BUN, and urine NGAL/urine Cr values did not differ significantly between and within patients with and without AKI., Conclusion: Our data suggested that the changing pattern of urine NGAL/urine Cr ratio did not differ significantly between the atorvastatin and placebo groups during the early phase of amikacin treatment., Competing Interests: There are no conflicts of interest.

Background and Objectives: The frequency of multi-drug resistant Acinetobacter spp . infections is increasing in Iran. Considering availability of limited therapeutic options, clinical response and outcome of ventilator-associated pneumonia due to multi-drug resistant A.baumannii were evaluated in critically ill patients., Materials and Methods: In this prospective study, 29 patients with carbapenem resistance A. baumannii ventilator-associated pneumonia were enrolled. Endotracheal aspirate specimens were analyzed according to the clinical and laboratory standard institute instructions in the hospital's microbiology laboratory. Demographics, clinical, microbiological and laboratory findings were collected for each patient during the treatment course. Therapeutic empirical regimen, change in antibiotic regimen following receiving antibiogram results, clinical and microbiological responses, duration of ICU stay and outcome were collected for each recruited individual., Results: All of A. baumanii isolates were resistant to pipracillin-tazobactam, ceftriaxon, amikacin and ciprofloxacin. The resistance rate of A. baumanii species was 41.4% for ampicillin/sulbactabm and 93.1% for meropenem. Patients received either meropenem/colistin (51.7%) or meropenem/ampicillin-sulbactam (48.3%) as the treatment regimens based on the antimicrobial susceptibility patterns of isolates. Ventilator-associated pneumonia clinical response, improvement and failure achieved in 15 (51.7%), 8 (27.6%) and 6 (20.7%) of the patients respectively. Microbiological eradication and intermediate status were observed in 9/29 (31%) and 11/29 (37.9%) of patients, respectively., Conclusion: The antibiotic regimens showed comparable efficacy in treatment of VAP due to MDR A. baumannii but mortality rate was high. Considering widespread and high mortality rates associated with MDR infections, applying infection control and antibiotic stewardship programs in hospitals are essential.

Critically ill patient transfer is potentially risky and may be lead to morbidity and mortality. Physicians' skill is very important for safe transport. We want to evaluate the effect of clinical course teaching on the promotion of physicians' abilities in the transport of critically ill patients. In an interventional study, 320 interns, male and female, were taught about patient transfer in two groups include in one day clinical course as the small group system (n=160) and other group the lecture base learning (n=160). In the clinical course, each participant under observation of an anesthesiologist in the operation room and ICU was acquainted with mask ventilation, intubation and learned to work with a defibrillator, infusion pump, portable ventilator and pulse oximeter. In lecture group, the anesthesiologist explained the topics by video and dummy. At the end of education course, the interns' abilities were evaluated based on checklist method and scored by the project colleague in all educational items. Three hundred twenty interns, 122 males, and 198 females; were enrolled, two groups. The clinical course training caused improvements in the interns' knowledge and abilities in intubation and use of the defibrillator and portable ventilator vs.lecture group significantly (P<0.005). The males were better than females in laryngoscopy, but the progress of the females was significantly better than males (P=0.003). The rate of adverse events was reduced significantly after clinical course teaching (P=0.041) Clinical course teaching could promote interns' clinical competencies in the transport of critically ill patients.

Background: Hematocrit (Hct) is an important parameter for optimal oxygenation during discontinuation from ventilator, but there is no consensus about its concentration and effectiveness on successful extubation., Objectives: The current study aimed to determine the role of Hct concentration on extubation failure in critically ill patients., Patients and Methods: The current prospective cohort study investigated the effect of age, gender and Hct level on successful extubation of 163 mechanically ventilated patients in Imam Khomeini hospital intensive care units (ICUs), Tehran, Iran. Following successful weaning process, the patients were classified into two groups on the basis of Hct level; 62 with an Hct level of 21% - 27% and the other 101 patients with Hct levels above 27%. The data were analyzed by chi-square test and multiple logistic regressions. A probability value of less than 0.05 was considered significant., Results: There was no significant association between the level of Hct concentration and extubation failure (8.9% vs. 9.2%, P = 0.507). Gender and age were significantly associated with extubation failure (OR = 9.1, P = 0.034, OR = 12.5, P = 0.014, respectively). Although the differences between, before and after extubation of PaO2 and P/F ratio, were of significant values between the two different groups of Hct (P = 0.001, P = 0.004 respectively), they had no effect on the failure of extubation (P= 0.259, P = 0.403, respectively)., Conclusions: Although some studies showed association between anemia and extubation failure, the current study could not confirm it. The study showed that males, regardless of the Hct level, had a better extubation success rate than those of females.

Background: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress., Materials and Methods: Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days., Results: Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004)., Conclusion: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients.

Invasive candidiasis (IC) is associated with high mortality in intensive care unit (ICU) patients. Timely diagnosis of this potentially fatal condition remains a challenge; on the other hand, the criteria for initiating empirical antifungal therapy in critically ill patients are not well defined in different patient population and ICU settings. Alongside the international guidelines, reaching regional and local consensus on diagnosis and management of IC in ICU setting is essential. This report summarizes our present status of IC management in ICU, considered by a group of Iranian experts in the fields of intensive care and infectious diseases. A round table of 17 experts was held to review the available data and discuss the optimal treatment strategies for IC in critical care setting. Comparative published data on the management of IC were analytically reviewed and the commonly asked questions about the management of IC in ICU were isolated. These questions were interactively discussed by the panel and audience responses were taken to consolidate point-to-point agreement with the panel arriving at consensus in many instances. The responses indicated that patients' risk stratification, clinical discretion, fungal diagnostic techniques and the empirical therapy for IC are likely to save more patients. Treatment options were recommended to be based on the disease severity, prior azole exposure, and the presence of suspected azole-resistant Candida species. This report was reviewed, edited and discussed by all participants to include further evidence-based insights. The panel expects such endorsed recommendations to be soon formulated for implementation across the country.

Study Objective: To evaluate the effects of topical atorvastatin on the healing process of pressure ulcers in critically ill patients., Design: Randomized, double-blind, placebo-controlled clinical trial., Setting: Medical-surgical intensive care unit of a university-affiliated teaching hospital in Tehran, Iran., Patients: One hundred four patients with stage I or II pressure ulcers, graded according to the 2-digit Stirling Pressure Sore Severity Scale., Intervention: Patients were randomized to receive topical atorvastatin 1% ointment (51 patients [atorvastatin group]) or placebo ointment (53 patients [control group]) applied once/day to pressure ulcers for 14 days in addition to standard care for pressure ulcers., Measurements and Main Results: The efficacy of each treatment was assessed on days 7 and 14. Efficacy was determined based on the degree of healing of the existing pressure ulcer by using the 2-digit Stirling scale. The baseline stage of the pressure ulcers did not differ significantly between the control and atorvastatin groups. However, the mean ± SD stage of pressure ulcers significantly decreased in the atorvastatin group compared with the control group on day 7 (0.97 ± 0.76 vs 1.74 ± 0.75, p<0.01) and day 14 (0.42 ± 0.67 vs 1.71 ± 0.78, p<0.01) of treatment. In addition, the mean ± SD surface areas of ulcers in the atorvastatin group were significantly declined compared with the control group after 7 days (5.55 ± 4.55 vs 9.41 ± 5.03 cm², p<0.01) and 14 days (3.72 ± 4.45 vs 10.41 ± 6.41 cm², p<0.01) of treatment., Conclusion: Topical application of atorvastatin ointment 1% for 14 days in addition to standard care significantly accelerated the healing of stage I or II pressure ulcers in critically ill patients., (© 2013 Pharmacotherapy Publications, Inc.)

Background: The aim of present study was to determine the impact of two different ICU management model, open and semi closed, on resources utilization in intensive care unit., Method: Retrospective cohort analysis using data from hospital database was applied to compare the effect of ICU management model on ICU length of stay and bed disposition of 1064 patients admitted to the general ICU of Imam Khomeini Hospital of Tehran, Iran during the two consecutive 12-month periods from Mar, 2009 to Feb, 2010., Results: In open and semi closed interval 380 and 684 patients were admitted to ICU respectively. There was no significant difference in age, gender and severity of illness (based on APACHE-II score) and nurse to bed ratio between two groups. Average ICU length of stay, net mortality rate and bed turnover rate were lower in semi closed model than open model management significantly (P<0.05)., Conclusion: Semi closed model improves patient care and lead to lower mortality rate and resources utilization too.

Objective: Phenytoin is an antiepileptic drug used widely for prophylaxis and treatment of seizure after neurotrauma. Phenytoin has a complex pharmacokinetics and monitoring of its serum concentrations is recommended during treatment. Total phenytoin concentration is routinely measured for monitoring of therapy. In this study, we evaluated the correlation between phenytoin total and free concentrations in neurotrauma critically-ill patients to determine whether the phenytoin total concentration is a reliable predictor of free drug, which is responsible for the therapeutic effects., Methods: A total of 40 adult head trauma patients evaluated for free (unbound) and total serum phenytoin concentrations. Patients were divided into two groups. Group A consists of 20 unconscious patients with severe head injury under mechanical ventilation and Group B consists of 20 conscious self-ventilated patients. Correlation and agreement between total and free phenytoin plasma concentrations were analyzed., Findings: Pearson correlation analysis and Bland-Altman test showed weak to moderate correlation (r = 0.528) and poor agreement between free and total phenytoin concentrations in patients with severe trauma and higher Acute Physiology And Chronic Health Evaluation II (APACHE II) scores (Group A) and good correlation (r = 0.817) and moderate agreement in patients with mild to moderate trauma and lower APACHE II scores (Group B)., Conclusion: Our results indicated that total phenytoin serum concentration is not a reliable therapeutic goal for drug monitoring in severely-ill head trauma patients even in the absence of hypoalbuminemia, renal and hepatic failure. It seems justifiable to measure free phenytoin concentration in all severely ill neurotrauma patients.

There is no randomized study carried out in order to compare their pharmacokinetic parameters although midazolam, as a sedative, has been widely administered via continuous infusion as well as intermittent bolus doses in mechanically ventilated critically ill patients. We prospectively investigated the effect of these two principal methods on pharmacokinetic parameters in 23 of mentioned patients (16 males, 7 females) with the mean (± SD) age of 41.22 ± 17.5. All patients received total dose of 72 mg throughout the test days, 9 of whom received 1 mg/h (continuous infusion) and the rest obtained 4 mg / 4 h (intermittent bolus doses). Blood samples were collected at 8 and 4 h prior to the end time of drug administration (zero time), zero time and 4, 8, 12, 20 and 30 h after it. APACHE (Acute Physiology and Chronic Health Evaluation) II required data was recorded daily and the patients' mean score was 16.26 ± 4.38. The mean (± SD) value of pharmacokinetic parameters of Midazolam in continuous infusion and intermittent bolus doses methods were as follows: (t½ = 17.88 ± 14.65 h, Cl = 21.80 ± 14.95 L/h) vs. (t½ = 19.74 ± 12.45 h, Cl = 29.43 ± 19.45 L/h). Volume of distribution (Vd) was measured in continuous infusion group which was 612.58 ± 582.93 L. The calculated clearance and half-life were found not to be significantly different (p < 0.05). The patients might be exposed to similar undesired effects due to the large volumes of distribution following the administration methods studied.

Background: Osmotherapy is a cornerstone for the management of severe Traumatic Brain Injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but there is inadequte knowledge regarding dose and its saftey in comparison to mannitol. S100B, as a specific neuroinflammatory biomarker in TBI might be a reliable therapeutic index following osmotic therapy., Aim: To compare both administration ways of HTS 5% (bolus and infusion) with mannitol upon S100B as a therapeutic tool for monitoring treatment in TBI patients., Method: Adult patients wih modrate to severe TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 hrs (N: 11) as bolus; 500 cc of HTS 5% (N: 12) as infusion for 24 hrs; or 1 g/kg mannitol of 20% (N: 10) as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 hrs based on patient's response for 3 days. Serum S100B, blood pressure, serum sodium and osmolality and Glascow coma score (GCS) were measured at baseline and daily for 3 days., Results: Initial serum S100B level in TBI patients was higher than control group (p < 0.0001). Levels of measured S100B have decreased for all treatment groups, but reduction wasn't significantly after hyperosmolal therapy. GCS level increased significantly in infusion group (p = 0.002) and there were negative and significant correlation between serum S100B level and GCS level in some days. Mean arterial pressure increased significantly in HTS groups (bolus: p = 0.002, infusion < 0.0001)., Conclusions: S100B is closely related to the pathophysiological mechanism in TBI and may be useful as a therapeutic tool for treatment monitoring in TBI patients HTS is a safe and effective osmotic agent in TBI setting.

Unlabelled: Severe sepsis involves a generalized inflammatory response, mediated by a number of various cytokines and factors. Plasma exchange (PE) has been proposed as a therapeutic approach to improve survival of patients with severe sepsis and septic shock. The theory is that removing harmful excessive endogenous inflammatory mediators is beneficial. Upon establishment of a diagnosis of severe sepsis, twelve patients received PE plus conventional sepsis treatment. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were assayed before and after each session of PE., Results: There were no significant changes in cytokine plasma levels after each PE session compared to pre-procedure levels. Among measured pro-inflammatory cytokines, only the plasma levels of IL-6 before the 2nd and 3rd PE sessions were lower than baseline levels (p=0.011 and p=0.012, respectively). All patients tolerated PE therapy well without any adverse effects or homodynamic instability. The results of this study showed that PE does not have a direct and rapid effect on plasma level of TNF-α, IL-1β and IL-6., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Stress-related mucosal damage (SRMD) is a significant cause of morbidity and mortality in critically ill patients due to the gastrointestinal blood loss. Prophylaxis of SRMD with proton pump inhibitors or histamine-2 blockers has gained widespread use in intensive care units. Both demonstrated to be effective in reducing clinically significant bleedings, while PPIs has shown to exert some anti inflammatory effects including the inhibition of producing pro-inflammatory cytokines. As cytokines have role in developing SRMD, the aim of this study was to evaluate the effect of PPIs on the inhibition of cytokine release following the critical illness. A total of 27 critically ill patients with risk factors of developing stress ulcer and intragastric pH < 3.0 enrolled to this Randomized clinical trial study. Patients were randomly assigned in three treatment groups; group one received 40 mg of intravenous pantoprazole every 12 h for 48 h (four doses), group two received 80 mg of intravenous pantoprazole every 24 h continuous infusion for 48 h and the third group received 150 mg of ranitidine intravenously as 24 h continuous infusion for 48 h. Plasma and gastric juice samples were obtained at 0th, 12th, 24th and 48th h for the measurement of EGF, IL-1β, IL-6, IL-10 and TNF-α. Pantoprazole infusion have decreased the plasma IL-1β concentrations (p = 0.041). No other significant differences in concentrations of EGF, IL-6, IL-10 and TNF-α were detected. There were reverse correlations between the intragastric pH with gastric juice IL-1β and TNF-α concentrations and a direct correlation between the intragastric pH and gastric juice EGF in pantoprazole groups. Our data suggest that pantoprazole may have some anti-inflammatory effects on patients. However, the exact impact of this effect on patients should be assessed by further studies.

Background and the Purpose of the Study: sepsis is one of the most widespread and lethal disease in Intensive Care Units (ICU). Based on pathophisyology of sepsis, it seems that routine laboratory tests combined with analysis of pro-inflammatory cytokines plasma levels, help clinicians to have more information about disease progress and its correct management., Methods: This was a prospective observational study to determine the predictive role of Tumor Necrosis Factor alpha (TNF-α), Interleukin (IL)-1β and IL-6 as three main pro-inflammatory cytokines and Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA) as two scoring systems in mortality of critically ill patients with severe sepsis. Fifty and five patients with criteria of severe sepsis were included in this study. An exclusion criterion was post Cardiopulmonary Resuscitation (CPR) status. Cytokines (TNF-α, IL-1β and IL-6) were assayed in the first, third and seventh days in blood of patients., Results and Major Conclusion: Among three measured cytokines, sequential levels of TNF-α and IL-6 showed significant differences between survivors and nonsurvivors. IL-6 had a good correlation with outcome and scoring systems during the period of this study. The areas under the receiver operating characteristic (AUROC) curve indicated that APACHE II (0.858, 0.848, 0.861) and IL-6 (0.797, 0.799, 0.899) had discriminative power in prediction of mortality during sequental measured days. Multiple logestic regression analysis identified that evaluation of APACHE II and TNF-α in the first day and APACHE II and IL-6 in the third and seventh days of severe septic patients are independent outcome predictors. Results of this study suggest that IL-6 and APACHE II are useful cytokine and scoring systems respectively in prediction of mortality and clinical evaluation of severe septic patients.

Purpose: Utilization of lead-contaminated opium may lead to severe motor neuron impairment and quadriplegia., Case Report: Forty years oriented old male, opium addict, was admitted to the ICU, with headache, nausea and abdominal pain, and weakness in his lower and upper extremities without definitive diagnosis. The past medical and occupational history was negative. Laboratory investigation showed; anemia (Hb 7.7 g/dl), slightly elevated liver function tests, elevated total bilirubin, and ESR. Abdominal sonography and brain CT scan were normal. EMG and NCV results and neurologic examination were suggestive for Guillain-Barre. He underwent five sessions of plasmapheresis. Blood lead level was > 200 microg/dl. He received dimercaprol (BAL) and calcium disodium edetate (CaEDTA) for two five days session. Upon discharge from ICU all laboratory tests were normal and blood lead level was reduced, but he was quadriplegic., Conclusion: The delayed treatment of lead poisoning may lead to irreversible motor neuron defect.