Cannabidiol Anticonvulsant Effects Against Lithium-Pilocarpine-Induced Status Epilepticus in Male Rats Are Mediated by Neuroinflammation Modulation and Cannabinoids 1 (CB1), But Not CB2 and GABAA Receptors.

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 GABAA 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)-lß and tumor necrosis factor (TNF)-α, using ELISA kits. Also we analyzed the expression of CB1, CB2, and GABAA 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-lß 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 GABAA 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-1ß and TNF-α markers independent of CB2 and GABAA receptors.

Effects of nebulized hypertonic saline on inflammatory mediators in patients with severe COVID-19 pneumonia: A double-blinded randomized controlled trial.

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, PO2, 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.

Gargle test for successful extubation in critically ill patients underwent head and neck surgeries: A new test.

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.

The effect of Vitamin C and Zn supplementation on the immune system and clinical outcomes in COVID-19 patients.

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.

Mortality Predictive Value of APACHE II and SOFA Scores in COVID-19 Patients in the Intensive Care Unit.

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.

The association between serum levels of micronutrients and the severity of disease in patients with COVID-19.

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, B9, B12, 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.

Pathological Findings of Postmortem Biopsies From Lung, Heart, and Liver of 7 Deceased COVID-19 Patients.

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.

Nutritional status of patients hospitalized in the intensive care unit: A comprehensive report from Iranian hospitals, 2018.

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.

Comparing efficacy of enteral nutrition plus ranitidine and enteral nutrition alone as stress ulcer prophylaxis.

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.

Clinical course teaching in transport of critically ill patients: Small group methods.

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.

Pro-inflammatory cytokine profile of critically ill septic patients following therapeutic plasma exchange.

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-1ß 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-1ß and IL-6.