Clinical and imaging features of patients with COVID-19 in a double-center cohort study.

INTRODUCTION: There is extensive published data on coronavirus disease 2019 (COVID-19). However, information on the effective factors that improve the pulmonary involvement of COVID-19 patients, and long-term clinical and imaging follow-up of these patients is limited. METHODOLOGY: This is a prospective cohort study on patients with COVID-19 who were hospitalized in two major academic hospitals in Yazd, Iran. The correlation between the baseline demographic and clinical/para-clinical data with the imaging resolution status at day 60 was assessed. RESULTS: 122 patients, including 65 males, with an average age of 53.43 years participated in this study. Age, gender, baseline oxygen saturation (O2Sat), and the percentage of lung involvement were the main prognostic factors. Our results suggest that with every year increase in age, the probability of complete imaging resolution decreases by 6.4%. In addition, women are 2.07 times more likely to recover completely. Moreover, each percent increase of baseline O2Sat makes the patients 15.4% more likely to fully recover. As the patients' shortness of breath increases, the probability of recovery decreases by 9.8%.;56.7% of patients who did not recover after 60 days had persistent shortness of breath, while only 21% of those who recovered had symptoms of dyspnea after day 60. CONCLUSIONS: Age, gender, baseline O2Sat, percentage of lung involvement, and shortness of breath were identified as the main risk factors in the recovery of patients with COVID-19. Long-term follow-up of patients with COVID-19, especially patients with high-risk factors, is necessary.

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.

Impact of vaccination status on clinical outcomes of hospitalized COVID-19 patients.

INTRODUCTION: It is important to identify the relationship between the COVID-19 vaccination status and the prognosis of this disease in hospitalized patients to gain a more accurate picture of their status and the effect of vaccination, as well as take necessary measures to improve their medical care. Thus, the present study was conducted to investigate the relationship between the vaccination status of hospitalized COVID-19 patients and the disease severity index in terms of clinical, imaging, and laboratory criteria. METHODS: This research is a descriptive-analytical cross-sectional study. the study population consisted of patients with a positive RT-PCR test for coronavirus, admitted to COVID-19 departments of teaching hospitals in Yazd, Iran, during two months in the sixth peak of COVID-19. The patients' data comprised demographic information (age, sex, and underlying disease), clinical information (length of hospital stay, length of ICU stay, and vaccination status), disease outcome (mortality and intubation), laboratory information (ESR, CRP, and NLR), and imaging information (lung involvement percentage), and finally, the relationship between patients' vaccination status and disease severity indices were analyzed with the chi-square test, independent t-test, and logistic regression analysis at a 95% confidence interval (CI). FINDINGS: According to research findings, the duration of hospitalization was 5.25 ± 2.34 and 6.11 ± 3.88 days in groups of patients with complete and incomplete vaccination, respectively (P = 0.003). The lengths of ICU stay were 6 ± 4.63 and 5.23 ± 3.73 days in both groups of patients admitted to the ICU (P = 0.395). Furthermore, there were significant relationships between the ICU admission rates, endotracheal intubation, mortality rate, the lung involvement score in the chest CT scan, and the NLR with the vaccination status.Multivariate regression analysis indicated that DM, IHD, NLR, CT scan score and vaccination status were related to patients' in-hospital mortality. CONCLUSION: Complete vaccination of COVID-19 led to a milder disease in terms of clinical, imaging, and laboratory criteria of patients and decreased the possibility of hospitalization in ICUs, intubation, and mortality in patients.

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.

Picture of the employment status of nurses in the world: Scoping review on pros and cons.

Nurses play a vital role in the delivery, quality improvement of healthcare services, and promoting patient health. Therefore, methods of providing nurses are an important issue. This study was conducted to collect evidence on the methods of providing nurses and their advantages and disadvantages by a scoping review method. The Arksey and O'Malley Framework and PRISMA were used in directing the present scoping review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to conduct the review and report on results. The ISI Web of science, PubMed, Scopus, and ProQuest electronic databases were searched for relevant articles published between January 2010 and December 2020 using the keywords and their synonyms. Finally, 19 articles out of 1813 ones to answer the research questions were selected. The results showed that although two general methods are for the employment status of nurses (full-time and part-time nurses), different classification countries are dissimilar from each other. A total of 13 advantages and 20 disadvantages of the part-time pattern and 6 advantages and 4 disadvantages were extracted from the full-time pattern of studies. None of the patterns has precedence over the other. Despite the strengths and weaknesses, each of the full-time or part-time patterns in its position is beneficial. With proper management and planning, it is possible to minimize their weaknesses and benefited from their advantages. Training part-time nurses to maintain and improve their level is a key point in reducing the disadvantages of this pattern.

Iranian health financing system challenges to promote health outcomes: Qualitative study.

BACKGROUND: Adequate health financing system should have key criteria and characteristics such as risk distribution over time, risk accumulation, sustainable resource provision, and resource allocation based on meeting essential needs. Weakness of the tariff system, lack of attention to strategic purchasing, inefficient allocation of manpower, and a weak payment system are among the problems within the Iranian financing system. Given the weaknesses of the current health financing system, it seems necessary to identify challenges and provide effective solutions to address them. MATERIALS AND METHODS: This qualitative study was conducted to explore the views of a group of 32 major policymakers and planners in the various departments and levels of the Ministry of Health, Universities of Medical Sciences, Medical System Organization, and Health Insurance Organization in Iran (n = 32), selected through purposive sampling. The data was collected through in-depth and semi-structured interviews and analyzed using Graneheim and Lundman's conventional content analysis methods. The trial version of MAXQDA 16 software was used to manage the coding process. RESULTS: Based on the results of data analysis, a total of 5 categories and 28 subcategories were obtained. In this study, five main categories were obtained through the content analysis method, including (1) stewardship; (2) providing services; (3) production of resources; (4) collecting resources; and (5) purchasing and allocation of resources. CONCLUSION: It is suggested that those in charge of the health system, following the reform of the organization of the health system, move toward the improvement and widespread implementation of the referral system and that clinical guidelines be carefully compiled. Also, appropriate motivational and legal tools should be used to implement them. However, insurance companies need to make cost, population, and service coverage more effective.

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.

Efficacy of curcumin for amelioration of radiotherapy-induced oral mucositis: a preliminary randomized controlled clinical trial.

BACKGROUND: Oral mucositis (OM) is one of the main problems in almost all patients undergoing head and neck radiotherapy (RT). Owning to the antioxidant and anti-inflammatory properties of curcumin, the effect of both oral and topical formulations of curcumin was assessed on radiation-induced OM (ROM) in this study. METHODS: The safety and efficacy of curcumin mouthwash 0.1% (w/v) and curcumin-nanocapsule were evaluated in ameliorating severity and pain/burning associated with OM during RT. The current randomized, placebo-controlled trial was conducted on 37 patients with head and neck cancers. Patients with grades 1 to 3 of ROM were randomized to receive one of the three interventions: curcumin mouthwash (0.1% w/v); Sinacurcumin soft gel containing 40 mg curcuminoids as nano-micelles (SinaCurcumin®40); or placebo mouthwash with a similar transparent appearance to curcumin mouthwash for 1 min three times daily during RT. Study evaluations were conducted at baseline and weekly thereafter for up to 3 weeks using the Numeric rating scale (NRS) and world health organization (WHO) scale. RESULTS: Among the 45 patients randomized, 37 (mean (SD) age of 53.36 (15.99) years; 14 [37.8%] women) completed the treatment according to the protocol. Patients treated with either oral or topical curcumin showed a significantly reduced severity and burning related to OM during the first 3 weeks after administration (P-Value < 0.001) as compared with the placebo. At study termination, more than 33% of subjects utilizing curcumin mouthwash and 15% of patients utilizing curcumin-nanocapsule remained ulcer free while all of the placebo-receiving subjects had OM. The reduction of NRS and WHO scale between curcumin groups was comparable without significant differences. CONCLUSION: Both curcumin mouthwash and nanocapsule were effective, safe, and well-tolerated in the treatment of radiation-induced OM. Higher doses of curcumin and larger sample sizes can be used for further investigation in future studies. TRIAL REGISTRATION: https://irct.ir/ IRCT20190810044500N17 (13/08/2021).

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.

Efficacy and safety of Tocilizumab, plasmapheresis and their combination in severe COVID-19: A randomized clinical trial.

BACKGROUND: This study sought to evaluate and compare the effectiveness of plasmapheresis, Tocilizumab, and Tocilizumab with plasmapheresis treatment on the removal of inflammatory cytokines and improvement clinically of patients with severe COVID-19 in Intensive Care Units (ICU) due to the association between increased cytokine release and the severity of COVID-19. METHODS: This clinical trial study was conducted in three treatment arms in Iran. All patients received standard care and randomization into one of three treatment groups; Tocilizumab (TCZ) alone, plasmapheresis alone, or a combination of Tocilizumab and plasmapheresis. Demographics, clinical evaluation, oxygenation status, laboratory tests and imaging data were evaluated in the three groups and re-checked 48 h after the end of treatment trials. Primary outcomes were oxygenation status, the need for mechanical ventilation and the rate of death. RESULTS: Ninety-four patients were included in the trial after meeting the eligibility requirements. Twenty-eight patients received Tocilizumab alone, 33 had plasmapheresis alone, and 33 received both Tocilizumab and plasmapheresis. Baseline characteristics did not differ between three groups that included demographic, clinical and laboratory parameters. Following therapy, there was no difference between the three groups for CRP, ferritin, d-dimer, IL-6, pro-calcitonin and neutrophil to lymphocyte ratio (NLR) (P > 0.05). While a significant reduction was found in CRP levels within each group (32.04 ± 42.43 to 17.40 ± 38.11, 51.28 ± 40.96 to 26.36 ± 33.07 and 41.20 ± 34.27 to 21.56 ± 24.96 in the tocilizumab, plasmapheresis, and combined group, respectively) (p < 0.05), procalcitonin levels were elevated significantly in the Tocilizumab group (0.28 ± 0.09 to 0.37 ± 0.11) (p < 0.05). Clinically there was no difference between the three groups following treatment for O2 saturation levels with supplementary oxygen at discharge, endotracheal intubation rate, use of NIVPP, mortality, mean hospital and ICU length of stay (p > 0.05). CONCLUSION: Study results showed that the reduction of serum inflammatory markers, the rate of intubation and therapeutic complications including death were no different between the three groups; however, CRP levels were significantly reduced in all three groups, indicating that the interventions reduced inflammation likely through a reduction in the cytokine storm, though clinical outcomes were unaffected.

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.

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.

Local Administration of Sodium Bicarbonate for Preventing COVID-19 Associated Mucormycosis.

Background: One important complication of the coronavirus disease 2019 (COVID-19) is COVID Associated Mucormycosis (CAM), especially in patients with conditions such as diabetes and in immunosuppressed patients. Systemic acidosis, hyperglycemia, and other biochemical factors such as free iron and ß-hydroxybutyrate (BHB) can play a role in this complication. Materials and Methods: Rhizopus oryzae was isolated from a patient at Masih Daneshvari Hospital microbiology laboratory and sub-cultured on the Potato Dextrose Agar (PDA) for 48 hours at 37 °C. Subsequently, Roswell Park Memorial Institute (RPMI) 1640 Broth medium buffered to pH 7.0 with 3-N-morpholino-propane sulfonic acid. Macrodilution and microdilution methods were performed with 8.4% sodium bicarbonate. After 24 hours of incubation at 35°C, the minimum inhibitory concentration (MIC) and the minimum fungicidal concentrations (MFC) were evaluated. Results: We found that the minimum inhibitory and fungicidal concentrations are at 1.05 % and 2.1 % respectively. Therefore, the minimum concentration is 2% sodium bicarbonate, which requires achieving the desired environmental pH for fungal inhibition and fungicidal effects. Conclusion: Regulation of systemic acidosis by sodium bicarbonate could be used to decrease the chance of mucormycosis. In addition, According to our study and some others, an alkaline environment can prevent fungal growth. We found that a minimum concentration of 2% sodium bicarbonate is required to achieve the desired mucosal pH to inhibit the fungus. Therefore, sodium bicarbonate inhalation, as a cost-effective and well-tolerated medicine, is a good candidate for the prevention of mucormycosis. In this regard, extensive clinical and laboratory research is needed to achieve more accurate doses and appropriate administration intervals.

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.