STING agonists as promising vaccine adjuvants to boost immunogenicity against SARS-related coronavirus derived infection: possible role of autophagy.

As a major component of innate immunity and a positive regulator of interferons, the Stimulator of interferon gene (STING) has an immunotherapy potential to govern a variety of infectious diseases. Despite the recent advances regarding vaccines against COVID-19, nontoxic novel adjuvants with the potential to enhance vaccine efficacy are urgently desired. In this connection, it has been well-documented that STING agonists are applied to combat COVID-19. This approach is of major significance for boosting immune responses most likely through an autophagy-dependent manner in susceptible individuals against infection induced by severe acute respiratory syndrome Coronavirus (SARS­CoV­2). Given that STING agonists exert substantial immunomodulatory impacts under a wide array of pathologic conditions, these agents could be considered novel adjuvants for enhancing immunogenicity against the SARS-related coronavirus. Here, we intend to discuss the recent advances in STING agonists' recruitment to boost innate immune responses upon vaccination against SARS-related coronavirus infections. In light of the primordial role of autophagy modulation, the potential of being an antiviral vaccine adjuvant was also explored.

Efficacy and safety of topical rosuvastatin & melatonin vs. placebo in patients with mild to moderate plaque psoriasis: A preliminary randomized double-blinded clinical trial.

BACKGROUND: Considering the pathogenesis of psoriasis and also the anti-oxidant, immunomodulatory, and anti-inflammatory properties of rosuvastatin and melatonin, the current clinical trial aimed to evaluate the efficacy of topical rosuvastatin and melatonin in patients with mild to moderate psoriasis. METHODS: The current randomized placebo-controlled clinical trial was conducted using a 3-arm parallel group included 77 adult patients (≥18 years old) with mild to moderate plaque psoriasis. Patients were randomized into a 1:1:1 ratio to one of three groups to receive one of the three interventions: melatonin cream, 5.0% (w/w), rosuvastatin cream, 5.0% (w/w), or placebo cream with a similar transparent appearance twice a day for 12 weeks. The primary outcome was severity of the disease using Psoriasis Area Severity Index (PASI). The secondary outcomes included the Dermatological Sum Score (DSS) to assess the erythema, scaling, and plaque elevation and the Dermatology Life Quality Index (DLQI). Photographs of the lesions were also taken at the baseline and at different periodic intervals thereafter. RESULTS: Among 77 randomized patients, 52 (mean (SD) age, 40.67 (10.85) years; 22 (42.30%) men) completed the study. A significant reduction of 45% (mean (SD) of 2.67 (0.98) to 1.74 (1.12)) and 70% (mean (SD) of 2.67 (0.98) to 1.31 (1.13)) in PASI score, and 46% (mean (SD) of 2.91(1.85) to 1.57 (1.11)) and 77% (mean (SD) of 2.91 (1.85) to 0.87 (0.67)) in DSS score on days 30 and 60 with rosuvastatin cream, 5% w/w (P < 0.001) compared with baseline was observed, respectively. Also a significant decrease of 35% (mean (SD) of 2.67 (0.98) to 1.74 (1.12)) and 51% (mean (SD) of 2.67 (0.98) to 1.31 (1.13)) in PASI score, and 40% (mean (SD) of 5.00 (1.58) to 3.00 (1.76))and 61% (mean (SD) of 5.00 (1.58) to 1.92 (1.71)) in DSS score on days 30 and 60 with melatonin cream, 5% w/w (P < 0.001) compared with baseline were observed, respectively. In each of the melatonin or rosuvastatin groups, DLQI improved significantly on days 30 (P < 0.0001) and 60 (P < 0.001) while the changes in the control group were not significant. CONCLUSION: The results of this clinical trial demonstrated that topical melatonin and rosuvastatin diminished the severity of mild to moderate plaque psoriasis with a satisfactory safety profile. Future clinical trials should assess both the long-term efficacy and safety of melatonin and rosuvastatin creams in larger study populations.

Therapeutic Role of HAT Therapy in Sepsis: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes the mortality and is effective in expediting the resolution of sepsis and septic shock or not. METHODS: The following databases of PubMed, Scopus, ISI Web of Science, and Google Scholar were explored until March 2021 for all existing literature related to this field. An automatic alert for all databases was also activated to update our search. Meta-analysis was performed on clinical trials and cohorts separately as well as on all the pooled populations. RESULTS: This study evaluated nine clinical trials (1358 participants) and nine cohorts (339,437 participants) and is the most comprehensive systematic review in this field. The results of our meta-analysis demonstrated a significant difference in the reduction of Sepsis-Related Organ Failure Assessment (SOFA) score changes (Δ-SOFA) over 72 h (Standard Mean Difference (SMD) = -0.429; 95% CI: -0.737, 0.120; P = 0.006), duration of vasopressor (VP) (SMD = -0.373; 95% CI: -0.619, -0.128; P = 0.003), and procalcitonin (PCT) clearance (SMD = 0.496; 95% CI: 0.061, 0.931%; P = 0.026). Considering the results of cohorts, HAT therapy was effective in the survival of intensive care units (ICUs) patients (OR = 0.641; 95% CI: 0.423-0.970, P = 0.035). However, no significant difference was observed between the intervention and control groups in hospital mortality (Odds Ratio (OR) = 0.811, 95% CI: 0.544-1.209, P = 0.304), 28- to 30-day mortality (OR = 1.000; 95% CI: 0.782-1.279, P = 0.998), new onset acute kidney injury requiring renal replacement therapy ((OR = 0.856, 95% CI: 0.526, 1.391; P = 0.529), in-hospital length of stay (LOS) (SMD = 0.090; 95% CI: -0.036, 0.216 days; P = 0.162), LOS in ICU (SMD = 0.016, 95% CI: -0.138, 0.170 days; P = 0.838), and mechanical ventilation-free days (SMD = 0.004; 95% CI: -0.154, 0.163 days; P = 0.956). CONCLUSION: Supplementation of septic and septic shock patients with HAT therapy has significant beneficial effects on SOFA score over 72 hours, duration of exogenous vasopressor infusion and procalcitonin clearance. Considering the results of cohort studies, supplementation with HAT is efficacious in reducing ICU mortality.

Promises and Pitfalls of Calcineurin Inhibitors in COVID-19: A Systematic Review and Meta-analysis of Controlled Trials.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a violent attack on the body that leads to multi-organ failure and death in COVID-19 patients. The aim of this study was to systematically review the existing literature on the potential benefits of calcineurin inhibitors (CIs) as anti-vascular endothelial growth factor (VEGF) agents in improving the clinical outcomes of COVID-19 patients. METHODS: We searched various databases, including PubMed, Scopus, ISI Web of Science, Google Scholar, Cochrane databases, and ClinicalTrials.gov from 31st December, 2019, to 3rd February, 2023, for relevant controlled trials. The quality of the evidence was assessed using the Cochrane Collaboration tool. Comprehensive Meta-Analysis Software was used for the statistical analyses using a random-effects model. RESULTS: Three trials enrolling 293 participants were reviewed in the present systematic review and meta-analysis. The results showed CIs to lead to a significant reduction in mortality rate [risk ratio (RR): 0.598, 95% CI: 0.404-0.885, P-value = 0.010] with a low between-study heterogeneity (Cochrane Q test: I 2 = 0.000%, P-value = 0.371). Pooled analysis of two studies (84 patients) illustrated that CIs could not significantly increase the rate of hospital discharge (RR: 1.161, 95% CI: 0.764-1.764, P-value = 0.485) and heterogeneity was not significant (Cochrane Q test: I 2 = 26.798%, P-value = 0.242). CONCLUSION: CIs are able to inhibit the virus nucleocapsid protein so that they can prevent replication and respiratory tract tissue damage caused by SARS-CoV-2. Based on the characteristics mentioned in detail, CIs can play a potential therapeutic role for COVID-19 patients.

The Potential of Cannabidiol for Acute Respiratory Distress Syndrome in COVID-19.

COVID-19 disease manifests itself in a wide range of signs and symptoms, beginning with mild symptoms, such as fever, cough, and dyspnea, progressing to acute respiratory distress syndrome (ARDS) and death in some cases. The cytokine storm, or an excess of cytokines released locally, is assumed to be the primary cause of ARDS and mortality in COVID-19 patients. To enhance the survival rate of COVID-19 patients, early management of the cytokine storm with immunomodulators is crucial. Although the effectiveness of some immunosuppressants, such as corticosteroids and tocilizumab, has been studied in clinical trials, the administration of these drugs should be exercised cautiously. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid from Cannabis sativa extracts with anti-inflammatory properties. This review is intended to discuss the possible utility of CBD for the management of COVID-19 patients, particularly those with ARDS.

Efficacy of topical atorvastatin-loaded emulgel and nano-emulgel 1% on post-laparotomy pain and wound healing: A randomized double-blind placebo-controlled clinical trial.

This study aimed to develop atorvastatin-loaded emulgel and nano-emulgel dosage forms and investigate their efficiency on surgical wound healing and reducing post-operative pain. This double-blind randomized clinical trial was conducted in a surgical ward of a tertiary care hospital affiliated with university of medical sciences. The eligible patients were adults aged 18 years or older who were undergoing laparotomy. The participants were randomized in a 1:1:1 ratio to one of three following groups of atorvastatin-loaded emulgel 1% (n = 20), atorvastatin-loaded nano-emulgel 1% (n = 20), and placebo emulgel (n = 20) twice a day for 14 days. The primary outcome was the Redness, Edema, Ecchymosis, Discharge, and Approximation (REEDA) scores to determine the rate of wound healing. The Visual Analogue Scale (VAS) and quality of life were the secondary outcomes of this study. A total of 241 patients assessed for eligibility; of them, 60 patients completed the study and considered for final evaluation. A significant decrease in REEDA score was observed on Days 7 (63%) and 14 (93%) of treatment with atorvastatin nano-emulgel (p-value < 0.001). A significant decrease of 57% and 89% in REEDA score was reported at Days 7 and 14, respectively, in atorvastatin the emulgel group (p-value < 0.001). Reduction in pain VAS in the atorvastatin nano-emulgel was also recorded at Days 7 and 14 of the intervention. The results of the present study suggested that both topical atorvastatin-loaded emulgel and nano-emulgel 1% were effective in acceleration of wound healing and alleviation of pain of laparotomy surgical wounds, without causing intolerable side effects.

Efficacy of the Novel Formulation of Topical Liothyronine and Liothyronine-Insulin in Mild to Moderate Diabetic Foot Ulcer: A Randomized, Triple-blind Clinical Trial.

BACKGROUND: Diabetic foot ulcer (DFU) is one of the challenging complications of chronic diabetes. OBJECTIVE: The study aimed to investigate whether liothyronine (T3) and liothyronine-insulin (T3/Ins) topical preparations could significantly reduce the healing time of DFU. METHODS: A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted on patients with mild to moderate DFU, over a lesion area of no greater than 100 cm2. The patients were randomized to receive T3, T3/Ins, or honey cream 10% as the routine of care twice a day. Patients were examined for tissue healing weekly for 4 weeks, or until the total lesion clearance was observed, whichever was earlier. RESULTS: Of 147 patients with DFUs, 78 patients (26 per group) completed the study and were included in the final evaluation. At the time of study termination, all participants in each of the T3 or T3/Ins groups were free of symptoms based on the REEDA score, while about 40% of participants in the control group were detected with each of grades 1, 2, or 3. A significant difference was observed on days 7, 14, and 21 of consumption of topical preparations (P-value < 0.001). The mean time to complete wound closure in the routine care group was about 60.6 days, while it was 15.9 and 16.4 days in T3 and T3/Ins groups, respectively. Within the T3 and T3/Ins groups, significant earlier wound closure was detected at day 28 (P-value < 0.001). CONCLUSION: T3 or T3/Ins topical preparations are effective for wound healing and acceleration of wound closure in mild to moderate DFUs.

Prevention of radiotherapy-related oral mucositis with zinc and polyherbal mouthwash: a double-blind, randomized clinical trial.

BACKGROUND: A significant percentage of head and neck cancer (HNCs) patients receiving RT experience oral mucositis (OM). This study aimed to evaluate the effect of the polyherbal (containing chamomile, peppermint oil, Aloe vera, and honey) and zinc mouthwashes in comparison to the control (chlorhexidine) and placebo groups for prevention of radiation-induced OM. METHODS: This study was a double-blinded randomized clinical trial, conducted on 67 patients with HNCs undergoing radiotherapy. The eligible participants were randomized to receive either one of the following; zinc sulfate, polyherbal, chlorhexidine (Vi-one 0.2% CHX), or placebo mouthwash for 6 weeks. Follow-up evaluation of oral hygiene and the checklists of OM and the intensity of pain were filled out according to WHO assessment tool, Oral Mucositis Assessment Scale (OMAS), and Visual Analog Scale (VAS) in all the participants weekly for seven consecutive weeks. RESULTS: The results of present clinical trial demonstrated that the use of either zinc sulfate or polyherbal mouthwash significantly reduced the scores of OM and the severity of pain during weeks 2 to 7 after consumption compared with the CHX or placebo mouthwashes (P < 0.05). According to the post hoc analysis and compared with the placebo, a significantly better result was reported for zinc sulfate and polyherbal mouthwashes at weeks 2 to 7, but not for the CHX mouthwash. CONCLUSION: This study showed that the use of zinc sulfate or polyherbal mouthwashes is effective in prevention of both OM severity scores and pain related to OM intensity at weeks 2 to 7 following consumption in HNCs patients. Trial registration IRCT20190123042475N1 and IRCT20190123042475N2. Registration date: 2019-06-09, 2019-07-26.

Investigating the effect of oral synbiotic on enteral feeding tolerance in critically ill patients: A double-blinded controlled clinical trial of gut microbiota.

BACKGROUND: Probiotics are beneficial live microorganisms that can modify the gut microbiota. It is assumed that they help improve enteral feeding intolerance (EFI) and nosocomial infections in critically ill patients. The present clinical trial aimed to investigate the efficacy of synbiotics in improving EFI and oropharyngeal aspiration in patients admitted to the intensive care unit (ICU). METHODS: This randomized clinical trial was conducted on 105 critically ill patients admitted to the ICU of a tertiary referral hospital affiliated with a medical university. The patients were randomly assigned to either a synbiotic or control group and underwent 7 days of investigation. The primary end point was reduced gastric residual volume, which is suggestive of an improvement in EFI. The secondary end point included requirement for prokinetics, frequency of aspiration, duration of mechanical ventilation, length of ICU stay, and level of consciousness. RESULTS: The present clinical trial showed that synbiotic intervention has resulted in a significantly diminished requirement for prokinetics (P = 0.019), fewer oropharyngeal aspirations (P = 0.01), improved volume of bolus administration, and decreased gastric residual volume during the 7-day follow-up period. The patients who received synbiotic had an improved level of consciousness (P = 0.01). CONCLUSION: This clinical trial showed that the prescription of synbiotic from the initial days of enteral feeding has resulted in a significantly diminished requirement for prokinetics, less oropharyngeal aspiration, decreased gastric residual volume, improved volume of bolus administration, and hence, better tolerance of enteral feeding.

Harnessing polyphenol power by targeting eNOS for vascular diseases.

Vascular diseases arise due to vascular endothelium dysfunction in response to several pro-inflammatory stimuli and invading pathogens. Thickening of the vessel wall, formation of atherosclerotic plaques consisting of proliferating smooth muscle cells, macrophages and lymphocytes are the major consequences of impaired endothelium resulting in atherosclerosis, hypercholesterolemia, hypertension, type 2 diabetes mellitus, chronic renal failure and many others. Decreased nitric oxide (NO) bioavailability was found to be associated with anomalous endothelial function because of either its reduced production level by endothelial NO synthase (eNOS) which synthesize this potent endogenous vasodilator from L-arginine or its enhanced breakdown due to severe oxidative stress and eNOS uncoupling. Polyphenols are a group of bioactive compounds having more than 7000 chemical entities present in different cereals, fruits and vegetables. These natural compounds possess many OH groups which are largely responsible for their strong antioxidative, anti-inflammatory antithrombotic and anti-hypersensitive properties. Several flavonoid-derived polyphenols like flavones, isoflavones, flavanones, flavonols and anthocyanidins and non-flavonoid polyphenols like tannins, curcumins and resveratrol have attracted scientific interest for their beneficial effects in preventing endothelial dysfunction. This article will focus on in vitro as well as in vivo and clinical studies evidences of the polyphenols with eNOS modulating activity against vascular disease condition while their molecular mechanism will also be discussed.

Putative Therapeutic Impact of Inflammasome Inhibitors against COVID-19-Induced ARDS.

Given the importance of COVID-19-induced ARDS, recently, researchers have strived to determine underlying mechanisms involved in the inflammatory responses. In this regard, inflammasomes possess a distinct priority for cytokine storm occurrence and, subsequently, ARDS progression in ill patients with SARS-CoV-2 infection. In this minireview, the characteristics of known inflammasome inhibitors and designed research in this field were concretely deciphered.

Effects of topical timolol for the prevention of radiation-induced dermatitis in breast cancer: a pilot triple-blind, placebo-controlled trial.

INTRODUCTION: Radiation therapy is one of the standard methods in the treatment of breast cancer. Radiotherapy-induced dermatitis (RID) is a common complication of radiotherapy (RT) resulting in less tolerance in RT and even discontinuation of treatment. Timolol is a ß-adrenergic receptor antagonist that presents the best wound healing effects on both chronic and incurable wound healing. Topical forms of timolol could be effective in the prevention of RID due to the role of ß-adrenergic receptors in skin cells and keratinocyte migration, as well as the anti-inflammatory effect of timolol. However, no placebo-controlled randomized trial is available to confirm its role. The current trial aimed to evaluate the efficacy of topical timolol 0.5% (w/w) on the RID severity and patients' quality of life (QOL). METHOD: Patients aged older than 18 years with positive histology confirmed the diagnosis of invasive and localized breast cancer were included. Patients were randomized based on the random number table to receive each of the interventions of timolol 0.5% (w/w) or placebo topical gels from the first day of initiation of RT and for 6 weeks, a thin layer of gel twice daily. Patients were asked to use a thin layer of gel for at least two hours before and after radiation therapy. Primary outcomes were acute radiation dermatitis (ARD) grade using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale and severity of desquamation based on Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Secondary outcomes were QOL based on Skindex16 (SD-16), maximum grade of ARD, and time of initial RD occurrence. RESULTS: A total of 64 female patients with an age range of 33 to 79 years were included. The means (SD) of age were 53.88 (11.02) and 54.88 (12.48) in the control and timolol groups, respectively. Considering the RTOG/EORTC and CTCAE scores the difference between groups was insignificant (P-Value = 0.182 and P-Value = 0.182, respectively). In addition, the mean (SD) of time of initial RID occurrence in placebo and timolol groups were 4.09 (0.588) and 4.53 (0.983) weeks, respectively (P-Value = 0.035). The maximum grade of RID over time was significantly lower in the timolol group. During the study period, 75.0% of patients in placebo groups had grade 2 of ARD while in the timolol group it was 31.3% (P-Value = 0.002). QoL was not significantly different between groups (P-Value = 0.148). CONCLUSION: Although the topical formulation of timolol, 0.5% (w/w), was found to reduce the average maximum grade of ARD and increase the mean (SD) time of initial RID occurrence, it showed no effect on ARD, severity, and QOL. However, future clinical trials should be performed to assess timolol gel formulation in larger study populations. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N11 (17/03/2021).

Evaluation of therapeutic effects of crocin in attenuating the progression of diabetic nephropathy: a preliminary randomized triple-blind placebo-controlled trial.

BACKGROUND: Diabetic nephropathy (DN) is one of the most important complications of type 2 diabetes (T2DM). Oxidative stress and inflammatory cytokines play an essential role in the development and progression of DN. Despite adopting appropriate therapies, many patients with DN progress to end-stage renal disease (ESRD). Therefore, exploring innovative strategies for better management of DN is crucial. Crocin, a natural compound found in saffron, has profound antioxidant, antifibrotic and anti-inflammatory properties. This study aimed to evaluate the therapeutic effects of crocin in attenuation of the progression of DN. METHODS: In this randomized, triple-blind, placebo-controlled clinical trial, 44 patients with T2DM and microalbuminuria were randomly assigned to receive either crocin (15 mg/day) or a placebo for 90 days. Eventually, 40 patients completed the study: 21 patients in the crocin group and 19 in the placebo group. The primary outcome was a change in urine Albumin-to-Creatinine Ratio (uACR) from baseline to the end of the treatment period. We also evaluated metabolic, anthropometric, and biochemical parameters as the secondary outcomes. RESULTS: The results of the present study showed that uACR increased in both groups, but the increment was not significantly higher in the crocin group compared with the placebo. Serum levels of transforming growth factor-ß (TGF-ß) decreased in the crocin group and increased in the placebo group, but none of these changes was significant. Crocin significantly reduced triglyceride (TG) as an important metabolic parameter (P-Value = 0.03). CONCLUSION: This study has shown that crocin may be a safe and potential adjunct to conventional therapies for DN patients but because of our limitations such as short duration of the treatment period, and prescribing low doses of crocin, we could not achieve the significant level.

Neurohormetic phytochemicals in the pathogenesis of neurodegenerative diseases.

The world population is progressively ageing, assuming an enormous social and health challenge. As the world ages, neurodegenerative diseases are on the rise. Regarding the progressive nature of these diseases, none of the neurodegenerative diseases are curable at date, and the existing treatments can only help relieve the symptoms or slow the progression. Recently, hormesis has increased attention in the treatment of age-related neurodegenerative diseases. The concept of hormesis refers to a biphasic dose-response phenomenon, where low levels of the drug or stress exert protective of beneficial effects and high doses deleterious or toxic effects. Neurohormesis, as the adaptive aspect of hormetic dose responses in neurons, has been shown to slow the onset of neurodegenerative diseases and reduce the damages caused by aging, stroke, and traumatic brain injury. Hormesis was also observed to modulate anxiety, stress, pain, and the severity of seizure. Thus, neurohormesis can be considered as a potentially innovative approach in the treatment of neurodegenerative and other neurologic disorders. Herbal medicinal products and supplements are often considered health resources with many applications. The hormesis phenomenon in medicinal plants is valuable and several studies have shown that hormetic mechanisms of bioactive compounds can prevent or ameliorate the neurodegenerative pathogenesis in animal models of Alzheimer's and Parkinson's diseases. Moreover, the hormesis activity of phytochemicals has been evaluated in other neurological disorders such as Autism and Huntington's disease. In this review, the neurohormetic dose-response concept and the possible underlying neuroprotection mechanisms are discussed. Different neurohormetic phytochemicals used for the better management of neurodegenerative diseases, the rationale for using them, and the key findings of their studies are also reviewed.

Pharmacotherapy consideration of thrombolytic medications in COVID-19-associated ARDS.

BACKGROUND: In late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is responsible for coronavirus disease (COVID-19), was identified as the new pathogen to lead pneumonia in Wuhan, China, which has spread all over the world and developed into a pandemic. Despite the over 1 year of pandemic, due to the lack of an effective treatment plan, the morbidity and mortality of COVID-19 remains high. Efforts are underway to find the optimal management for this viral disease. MAIN BODY: SARS-CoV-2 could simultaneously affect multiple organs with variable degrees of severity, from mild to critical disease. Overproduction of pro-inflammatory mediators, exacerbated cellular and humoral immune responses, and coagulopathy such as Pulmonary Intravascular Coagulopathy (PIC) contributes to cell injuries. Considering the pathophysiology of the disease and multiple microthrombi developments in COVID-19, thrombolytic medications seem to play a role in the management of the disease. Beyond the anticoagulation, the exact role of thrombolytic medications in the management of patients with COVID-19-associated acute respiratory distress syndrome (ARDS) is not explicit. This review focuses on current progress in underlying mechanisms of COVID-19-associated pulmonary intravascular coagulopathy, the historical use of thrombolytic drugs in the management of ARDS, and pharmacotherapy considerations of thrombolytic therapy, their possible benefits, and pitfalls in COVID-19-associated ARDS. CONCLUSIONS: Inhaled or intravenous administration of thrombolytics appears to be a salvage therapy for severe ARDS associated with COVID-19 by prompt attenuation of lung injury. Considering the pathogenesis of COVID-19-related ARDS and mechanism of action of thrombolytic agents, thrombolytics appear attractive options in stable patients without contraindications.

Evaluation of family planning methods in married women with epilepsy.

BACKGROUND: Epilepsy is one of the most common neurologic unit diseases that have different prevalence in different parts of the world. Antiepileptic drugs (AEDs) are associated with major fertility risks for women of childbearing age. Due to the fact that studies on family planning methods in married women with epilepsy (WWE) have not been conducted in Iran, the aim of this study was to evaluate the family planning methods in married WWE in Birjand, Iran. METHODS: An analytical-descriptive study was performed on 126 married WWE hospitalized in the neurology ward or referred to Vali-e-Asr specialized and sub-specialized clinic in Birjand. Demographic information of patients as well as data on the type of used AED, and various methods of family planning were collected in a questionnaire. Data analysis was performed using Chi-square and Fisher tests. All of the above analyses were considered at a significance level of less than 5% by SPSS v.19 software. RESULTS: The mean age of the patients was 33.41 ±â€¯9.15 years. The mean age of experiencing the first seizure and the onset of menstruation were 24.82 and 13.79 years, respectively. Fifty (35.5%), 38 (27%), 15 (10.6%), 14 (9.9%), and 14 (9.9%) patients used sodium valproate, carbamazepine, phenytoin, levetiracetam, and lamotrigine, respectively. The results showed that 72 sexually active patients (70.6%) used family planning methods, of which 43 patients (59.7%) used withdrawal method, 20 patients (27.8%) used condoms, and 6 patients (8.3%) used oral contraceptive pills (OCP). Eight patients (9.6%) had a history of unintended pregnancy and 3 patients (3.6%) had a history of abortion. CONCLUSION: It is recommended to apply effective family planning methods in married WWE to prevent unintended pregnancies and the subsequent adverse effects in the fetus, considering the fact that a significant percentage of WWE did not use effective family planning methods and 8 cases of unintended pregnancies were reported. Because of high consumption of valproate in women of childbearing age in our study and concerning issue about its fetal malformation, it is recommended to reduce the administration of valproate in this population. Moreover, regarding the low consumption of folic acid, especially for women of childbearing age and pregnant WWE who are taking AED, the necessary recommendations should be made by our physicians.

Efficacy and safety of colchicine treatment in patients with COVID-19: A prospective, multicenter, randomized clinical trial.

Colchicine has shown clinical benefits in the management of COVID-19 via its anti-inflammatory effect. However, the exact role of colchicine in COVID-19 patients is unknown. The current clinical trial was performed on 202 patients with moderate to severe COVID-19. Patients were randomly assigned in a 1:1 ratio to receive up to a 3-day course of 0.5 mg colchicine followed by a 12-day course of 1 mg colchicine in combination with standard care or a 15-day course of standard care. Among 202 randomized patients, 153 completed the study and received colchicine/standard care or continued standard care (M age, 54.72 [SD, 15.03] years; 93 [63.1%] men). On day 14, patients in the colchicine/standard care group had significantly higher odds of a better clinical status distribution on chest CT evaluation (p = .048). Based on NYHA classification, the percentage change of dyspnea on day 14 between groups was statistically significant (p = .026), indicating a mean of 31.94% change in the intervention group when compared with 19.95% in the control group. According to this study, colchicine can improve clinical outcomes and reduce pulmonary infiltration in COVID-19 patients if contraindications and precautions are considered and it is prescribed at the right time and in appropriate cases.

Efficacy of combination triple therapy with vasopressin, steroid, and epinephrine in cardiac arrest: a systematic review and meta-analysis of randomized-controlled trials.

BACKGROUND: This study investigated whether combination therapy with vasopressin, steroid, and epinephrine (VSE) improves in-hospital survival and return of spontaneous circulation (ROSC) during and after resuscitation in-hospital cardiac arrest (CA). MATERIALS AND METHODS: Various databases were explored from inception until October 2021 for relevant published clinical trials and cohort studies. RESULTS: Three clinical trials were included. Pooled analysis suggested that VSE was significantly associated with increased ROSC in patients with in-hospital CA (IHCA) (odds ratio (OR): 2.281, 95% confidence interval (CI): 1.304-3.989, P value = 0.004). Meta-analysis of two studies (368 patients) demonstrated a significant difference in the reduction of mean arterial pressure (MAP) during and 15-20 min after cardiopulmonary resuscitation (standardized mean difference (SMD): 1.069, 95% CI: 0.851-1.288, P value < 0.001), renal failure free days (SMD = 0.590; 95% CI: 0.312-0.869 days; P value < 0.001), and coagulation failure free days (SMD = 0.403; 95% CI: 0.128-0.679, P value = 0.004). However, no significant difference was observed for survival-to-discharge ratio (OR: 2.082, 95% CI: 0.638-6.796, P value = 0.225) and ventilator free days (SMD = 0.201, 95% CI: - 0.677, 1.079 days; P value = 0.838). CONCLUSIONS: VSE combination therapy during and after IHCA may have beneficial effects in terms of the ROSC, renal and circulatory failure free days, and MAP. Prospero registration: CRD42020178297 (05/07/2020).

The preventive effect of the combination of atorvastatin and nortriptyline in migraine-type headache: a randomized, triple-blind, placebo-controlled trial.

BACKGROUND AND PURPOSE: Migraine ranked as the eighth cause of disability worldwide. Statins with anti-inflammatory and vasodilatory endothelial effects have been introduced as an option for the prevention of migraine-type headaches. The current study aimed to assess the efficacy and tolerability of atorvastatin for the prevention of migraine in adults. METHOD: This prospective, triple-blind, randomized controlled clinical trial was performed in adult migraineurs from mid-July 2019 to late-April 2020. Patients were randomly assigned to receive atorvastatin or placebo in combination with nortriptyline for 24-weeks. The frequency of headache was the primary outcome, and intensity of the headache and quality of life (QOL) were the secondary outcomes for this study. RESULTS: With 34 patients in each arm, 68 patients with migraines based on the International Headache Society (IHS) criteria were enrolled in the study. At week 24, patients in the atorvastatin group experienced significantly fewer migraine attacks than the placebo group (P-value = 0.004). Moreover, there were significant differences between the two groups in QOL at follow-up intervals of 14 (P-value = 0.001) and 24 (P-value < 0.001) weeks. However, no significant difference was observed in the intensity of headache was observed in both groups (P-value > 0.05). The most common adverse effects in intervention and control groups were constipation and insomnia, respectively. CONCLUSION: In patients with migraine, prophylaxis with atorvastatin significantly improved the frequency of headache and QOL over 24 weeks compared with placebo with no effect on the intensity of headache. Statins seem to be a potential promising drug for prophylaxis of migraine headaches.