Purpose: Given the coronavirus disease 2019 (COVID-19) pandemic, there is a global urgency to discover an effective treatment for patients withthis disease. This study aimed to evaluate the effects of the widely used antiparasitic drug ivermectin on outcomes in patients with COVID-19.Methods: In this randomized, double-blind clinical trial, patients with COVID-19 admitted to 2 referral tertiary hospitals in Mazandaran, Iran, were randomly divided into 2 groups: intervention and control. In addition to standard treatment for COVID-19, the intervention group received a single weight-based dose (0.2 mg/kg) of ivermectin; the control group received the standard of care. Demographic, clinical, laboratory, and imaging data from participants were recorded at baseline. Patients were assessed daily for symptoms and disease progression. The primary clinical outcome measures were the durations of hospital stay, fever, dyspnea, and cough; and overall clinical improvement.Findings: Sixty-nine patients were enrolled (mean [SD] ages: ivermectin, 47. 63 [22.20] years; control, 45.18 [23.11] years; P = 0.65). Eighteen patients (51.4%) in the ivermectin group and 18 (52.9%) in control group were male ( P = 0.90). The mean durations of dyspnea were 2.6 (0.4) days in the ivermectin group and 3.8 (0.4) days in the control group ( P = 0.048). Also, persistent cough lasted for 3.1 (0.4) days in the ivermectin group compared to 4.8 (0.4) days in control group (P P = 0.019). The mean durations of hospital stay were 7.1 (0.5) days versus 8.4 (0.6) days in the ivermectin and control groups, respectively ( P = 0.016). Also, the frequency of lymphopenia decreased to 14.3% in the ivermectin group and did not change in the control group ( P = 0.007).Implications: A single dose of ivermectin was well-tolerated in symptomatic patients with COVID-19, and important clinical features of COVID-19 were improved with ivermectin use, including dyspnea, cough, and lymphopenia. Further studies with larger sample sizes, different drug dosages, dosing intervals and durations, especially in different stages of the disease, may be useful in understanding the potential clinical benefits ivermectin. Iranian Registry of Clinical Trials identifier: IRCT20111224008507N3.

BackgroundHigh prevalence of hepatocellular carcinoma (HCC) and typically poor prognosis of this disease that lead to late stage diagnosis when potentially curative therapies are least effective; therefore, development of an effective and systematic treatment is an urgent requirement.Main bodyIn this review, several current treatments for HCC patients and their advantages or disadvantages were summarized. Moreover, various recent preclinical and clinical studies about the performances of “two efficient agents, sorafenib or natural killer (NK) cells”, against HCC cells were investigated. In addition, the focus this review was on the chemo-immunotherapy approach, correlation between sorafenib and NK cells and their effects on the performance of each other for better suppression of HCC.ConclusionIt was concluded that combinational therapy with sorafenib and NK cells might improve the outcome of applied therapeutic approaches for HCC patients. Finally, it was also concluded that interaction between sorafenib and NK cells is dose and time dependent, therefore, a careful dose and time optimizing is necessary for development of a combinational immune-cell therapy.

Background Although symptoms and signs of COVID-19 (Coronavirus disease 2019) in children are milder than adults, there are reports of more severe cases which were defined as pediatric inflammatory multisystem syndrome (PIMS). The purpose of this report was to describe the possible association between COVID-19 and PIMS in children. Methods From 28 March to 24 June 2020, 10 febrile children were admitted with COVID-19 infection showing characteristics of PIMS in Buali tertiary hospital of Sari, in Mazandaran province, northern Iran. Demographic and clinical characteristics, laboratory and imaging findings, and therapeutic modalities were recorded and analyzed. Results The mean age of the patients was 5.37 ± 3.9 years (13 months to 12 years). Six of them were boys. Kawasaki disease, myocarditis, toxic shock syndrome, appendicitis, sepsis, urosepsis, prolonged febrile seizure, acute hemorrhagic edema of infancy, and COVID-19-related pneumonia were their first presentation. All of them had increased C-reactive protein levels, and most of them had elevated erythrocyte sedimentation rate, lymphopenia, anemia, and hypoalbuminemia. Three of them had thrombocytopenia(PLT < 106). Six of them were serologically or polymerase chain reaction positive for COVID-19, and 4 of them were diagnosed as COVID-19 just by chest computed tomography scan. Most of the patients improved without a residual sequel, except one who died with multiorgan failure and another case was discharged with a giant coronary aneurysm. Conclusions Children with COVID-19 may present symptoms similar to Kawasaki disease and inflammatory syndromes. PIMS should be considered in children with fever, rash, seizure, cough, tachypnea, and gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain.

Objective. Since December 2019, the coronavirus disease 2019 (COVID-19) has been spread rapidly all over the world, infecting all age groups with this novel virus. In this manuscript, we report characteristics of children with COVID-19 in Mazandaran province, northern Iran. Method. From 12 February to 28 July 2020, medical records of 100 children diagnosed with COVID-19 admitted to the hospitals of Mazandaran province were collected. Patients’ age, gender, clinical symptoms, and signs, in addition to therapeutic management and outcomes, were reported. Results. 57 (57%) boys and 43 girls with the mean age of 104.63 ± 79.14 months were evaluated. 20 patients (20%) were transferred to the PICU (pediatric intensive care unit), and 13 children experienced a severe form of the disease, pediatric inflammatory multisystem syndrome (PIMS). The mean duration of hospitalization was 5.3 ± 4.7 days. Fever (81%), respiratory (79%), gastrointestinal (47%), and neurologic complaints (29%) were experienced by the patients in addition to skin rash (14%). Sixty-two patients needed supplemental oxygen, and 6 of them underwent endotracheal intubation. Leukopenia was reported in 7, anemia in 24, and thrombocytopenia in 12 patients. 4 patients with underlying diseases including chronic renal failure, Down syndrome with cerebral palsy, and morbid obesity died. Conclusion. COVID-19 can cause symptoms in children in two stages. In the first week, upper and lower respiratory symptoms can occur which has lower severity and prevalence compared to adults. But after 2-3 weeks following infection, symptoms of MIS-C or multisystem involvement can occur and COVID-19 should be considered. The most common indication for admission is fever, rash, and respiratory problems.

Polymeric forms of ionic liquids have many potential applications because of their ionic nature. Two ionic liquid monomers, 1-(4-vinylbenzyl)-3-methyl imidazolium hexafluorophosphate (VMIH) and 1-(4-vinylbenzyl)-4-(dimethylamino)-pyridinium hexafluorophosphate (VDPH), were synthesized through the quaternization of N-methylimidazole and 4-(dimethylamino) pyridine with 4-vinylbenzylchloride, respectively, and a subsequent anion exchange reaction with potassium hexafluorophosphate. The homopolymers of VMIH, VDPH, and its copolymers with methyl styrene (in various mole ratios) were synthesized by free radical polymerizations at 70°C using α,α′-azobis(isobutyronitrile) as an initiator. Anionic drug molecule, naproxen (an anti-inflammatory drug), was effectively loaded into these positive charges polymers (PCP) and remained inside of the PCP under acidic environment (pH 2-6.5). The amount of loading of drug was increased with increasing positive charge densities resulting from the increasing number of ionic liquids groups. PCP as a controllable release of anionic drug molecules can be used as an oral delivery drug systems targeting at intestine. This drug can be remained trapped in the polymers when passing through the acidic and neutral environment and be released in intestine, where the environmental pH is close to basic.

A library of some new fluorescent chromenopyrimidine derivatives has been synthesized by new approaches. Water-promoted and one-pot reaction can produce new dialkylylamino)-5H-chromeno[2,3-d]pyrimidin-2-yl) phenols. These compounds can also be produced using domino reaction. Two parallel methods are compared. Novel N-alkyl-N-phenyl-5H-chromeno[2,3-d]-pyrimidin-4-amines and 4-alkoxy-5H-chromeno[2, 3-d]pyrimidines are synthesized by Lewis-acid catalyzed reactions. The fluorescence emission intensity of the four compounds from each of libraries after excitation in 290 nm is measured. Compound 2-(4,5-bis(N-methyl-N-phenylamino)-5H-chromeno[2,3-d]pyrimidin-2-yl)phenol was isolated as a byproduct. The details of an interesting exchangeable intramolecular H- bonding of two of the new compounds are reported by X-ray analysis data.

BackgroundIvermectin which was widely considered as a potential treatment for COVID-19, showed uncertain clinical benefit in many clinical trials. Performing large-scale clinical trials to evaluate the effectiveness of this drug in the midst of the pandemic, while difficult, has been urgently needed.MethodsWe performed two large multicenter randomized, double-blind, placebo-controlled clinical trials evaluating the effectiveness of ivermectin in treating inpatients and outpatients with COVID-19 infection. The intervention group received ivermectin, 0.4mg/kg of body weight per day for 3 days. In the control group, placebo tablets were used for 3 days.ResultsData for 609 inpatients and 549 outpatients were analyzed. In hospitalized patients, complete recovery was significantly higher in the ivermectin group (37%) compared to placebo group (28%; RR, 1.32 [95% CI, 1.04–1.66]; p-value = 0.02). On the other hand, the length of hospital stay was significantly longer in the ivermectin group with a mean of 7.98 ± 4.4 days compared to the placebo receiving group with a mean of 7.16 ± 3.2 days (RR, 0.80 [95% CI, 0.15–1.45]; p-value = 0.02). In outpatients, the mean duration of fever was significantly shorter (2.02 ± 0.11 days) in the ivermectin group versus (2.41 ± 0.13 days) placebo group with p value = 0.020. On the day seventh of treatment, fever (p-value = 0.040), cough (p-value = 0.019), and weakness (p-value = 0.002) were significantly higher in the placebo group compared to the ivermectin group. Among all outpatients, 7% in ivermectin group and 5% in placebo group needed to be hospitalized (RR, 1.36 [95% CI, 0.65–2.84]; p-value = 0.41). Also, the result of RT-PCR on day five after treatment was negative for 26% of patients in the ivermectin group versus 32% in the placebo group (RR, 0.81 [95% CI, 0.60–1.09]; p-value = 0.16).ConclusionOur data showed, ivermectin, compared with placebo, did not have a significant potential effect on clinical improvement, reduced admission in ICU, need for invasive ventilation, and death in hospitalized patients; likewise, no evidence was found to support the prescription of ivermectin on recovery, reduced hospitalization and increased negative RT-PCR assay for SARS-CoV-2 5 days after treatment in outpatients. Our findings do not support the use of ivermectin to treat mild to severe forms of COVID-19.Clinical Trial Registrationwww.irct.ir IRCT20111224008507N5 and IRCT20111224008507N4.

Background: Although symptoms and signs of COVID-19 (Coronavirus disease 2019) in children are milder than adults, there are reports of more severe cases which were defined as pediatric inflammatory multisystem syndrome (PIMS). The purpose of this report was to describe the possible association between COVID-19 and PIMS in children. Methods: From 28 March to 24 June 2020, 10 febrile children were admitted with COVID-19 infection showing characteristics of PIMS in Buali tertiary hospital of Sari, in Mazandaran province, northern Iran. Demographic and clinical characteristics, laboratory and imaging findings, and therapeutic modalities were recorded and analyzed. Results: The mean age of the patients was 5.37±3.9 years (13 months to 12 years). Six of them were boys. Kawasaki disease, myocarditis, toxic shock syndrome, appendicitis, sepsis, urosepsis, prolonged febrile seizure, acute hemorrhagic edema of infancy, and COVID-19-related pneumonia were their first presentation. All of them had increased C-reactive protein levels, and most of them had elevated erythrocyte sedimentation rate, lymphopenia, anemia, and hypoalbuminemia. Three of them had thrombocytopenia(PLT<106). Six of them were serologically or polymerase chain reaction positive for COVID-19, and 4 of them were diagnosed as COVID-19 just by chest computed tomography scan. Most of the patients improved without a residual sequel, except one who died with multiorgan failure and another case was discharged with a giant coronary aneurysm.Conclusion: Children with COVID-19 may present symptoms similar to Kawasaki disease and inflammatory syndromes. PIMS should be considered in children with fever, rash, seizure, cough, tachypnea, and gastrointestinal symptoms such as vomiting, diarrhea, and abdominal pain.