Acute Hepatitis A and Hepatitis B Coinfection in a Young Female: A Case Report and Literature Review.

Background: Hepatitis is one of the common infectious diseases that can infect patients in various forms. Based on their characteristics and clinical features, they can cause irreparable complications in patients. Coinfections and superinfections between its variant have been reported, but the coinfection of acute HAV and HBV is rarely reported. Case Presentation. In this case report, we presented a case with severe malaise, nausea, vomiting, generalized jaundice, and a history of recent tattooing and travel to the HAV endemic area. In our evaluation, she had a positive HBsAg, HBeAg, anti-HBs IgM, anti-HAV IgM, and negative result in HCV antibody, HIV antibody, and anti-HAV IgG. The coinfection of HAV/HBV was confirmed for her. Conclusion: Physicians should differentiate hepatitis A and hepatitis B superinfection or coinfection, based on history and laboratory testing, to prevent complications with appropriate treatment.

Unexpected high frequency of anti-thyroid peroxidase (anti-TPO) antibodies in Golestan province, Iran.

Background: Anti-TPO antibodies are one of the characteristic factors in autoimmune thyroiditis (AIT). Previous studies reported a high prevalence of anti-TPO antibodies (Abs) in Iran. We have therefore assessed the prevalence of anti-TPO Abs in Gorgan, Iran. Methods: This cross-sectional study, conducted from 2015 to 2018 in Gorgan city, Northeast of Iran. The Participants included women with Poly cystic ovary syndrome (PCOs), celiac patients, men with hepatitis C infection, and age and sex-matched controls. ELISA method was used for the analysis of laboratory tests. Results: The number of enrolled subjects in PCOs, celiac disease, and Hepatitis C infection groups were 76, 67, and 60, respectively. Anti-TPO Abs positivity was significantly higher in patients with PCOS than in the control group (18.4% vs. 0.00%; p = 0.000). There were no significant differences in the frequency of anti-TPO Abs positive cases between CD patients and the controls (26.9% vs. 21.1% p =0.413). The incidence of anti-TPO Abs positivity was significantly higher in the control group (10% vs. 25%; P = 0.031). Conclusion: Very high level of anti-TPO Abs was observed in both patients and healthy population in Golestan province. Considering this rate and its association with autoimmune disorders, it is suggested to prioritize screening programs for related disease in this area.

Euglycemic diabetic ketoacidosis and COVID-19 management in a term pregnant patient; a case report.

In this case report, we report a Covid-19 infected female patient with gestational diabetes mellitus with primary manifestation of ketoacidosis at term pregnancy and discuss the management challenges with euglycemia and a high ketone burden.

Decreased Serum Selenium Levels of COVID-19 Patients in Comparison with Healthy Individuals.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the COVID-19 pandemic and is the cause of increased mortality, especially among elderly patients and those who have severe complications, such as chronic pulmonary obstruction, hypertension, diabetes, and cancer. Nutrition, especially micronutrients, plays an important role in reducing mortality and complications from COVID-19 because micronutrients strengthen our immune system and nutritional status is an important factor that affects the outcome of patients with COVID-19. Among micronutrients, selenium has an important effect on both intrinsic and acquired immunity. Host selenium deficiency affects the viral genome and increases the virulence of viruses. We have investigated the serum selenium levels in COVID-19 patients and healthy control individuals. METHODS: A total of 50 patients with COVID-19 infection were included in this study. During hospitalization, 13 patients died (non-survivor group) and 37 patients recovered (survivor group). We assessed the serum selenium levels in 50 COVID-19 patients and 50 healthy individuals by Agilent SpectrAA-240 Z atomic absorption spectrometer. RESULTS: The serum selenium level was significantly lower in COVID-19 patients (77. 8 ± 13.9 µg/L) as compared to healthy control individuals (91.7 ± 16.7 µg/L), but there was no significant difference between the survivor and non-survivor groups. Also, there was no significant relationship between serum selenium levels and laboratory findings of COVID-19 patients. CONCLUSIONS: These results suggest that decreased serum selenium levels may be a risk factor for the COVID-19 infection, but there was no significant relationship between selenium and severity and mortality of COVID-19 disease.

Clinical Presentations of the Survivor and Non-survivor Hospitalized Patients with COVID-19 in the Golestan Province of Iran during the First Peak of the Epidemics.

Background: Considering the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, which causes coronavirus disease 2019 (COVID-19), we aimed to report the clinical features of 427 patients with COVID-19 and the outcomes after one-month admission to major teaching hospitals in the northeast of Iran. Materials and Methods: Data of patients hospitalized with COVID-19 from 20 February 2020 to 20 April 2020 was analyzed using the R software. The cases and their outcomes were monitored up to one month following their admission. Results: Among 427 patients with a median age of 53 years (50.8% male), 81 (19%) were directly admitted to the ICU ward, and 68 (16%) died during the study. The mean (SD) lengths of hospital stay were significantly higher in the non-survivors (6 (9) days) than survivors (4 (5) days) (P = 0.018). Ventilation need was reported in 67.6% of the non-survivors and 0.8% of the survivors (P < 0.001). Cough (72.8%), fever (69.3%), and dyspnea (64.0%) were the most common symptoms. There were more comorbidities in the severe cases (73.5%) and non-survivor (77.5%). Liver and kidney damage were significantly more common in non-survivors. Ninety percent of the patients had at least one abnormal chest CT scan finding, including crazy paving and consolidation patterns (27.1%), followed by the ground-glass opacity (24.7%). Conclusion: Results showed that the patients' age, underlying comorbidities, levels of SpO2, and laboratory findings at the time of admission may predict the progress of the disease and can be considered mortality-related factors.

Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO2) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. EXCLUSION CRITERIA: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours' time of admission. The intervention begins with the administration of dexamethasone based on the SpO2 levels. If the level of SpO2 does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours' time of admission and will be continued for 48-72 hours and then the SpO2 level will be checked. Then, if the level of SpO2 has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO2 level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO2 level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug's bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.

Encapsulation of Leflunomide (LFD) in a novel niosomal formulation facilitated its delivery to THP-1 monocytic cells and enhanced Aryl hydrocarbon receptor (AhR) nuclear translocation and activation.

BACKGROUND: Leflunomide (LFD) is an Aryl hydrocarbon receptor (AhR) agonist and immunomodulatory drug with several side effects. Niosomes are novel drug delivery systems used to reduce the unfavorable effects of drugs by enhancing their bioavailability, controlling their release and targeting specific sites. OBJECTIVES: Here, we prepared niosomal formulations of LFD, evaluated their properties and delivered to THP-1 monocytic cells to study the activation and nuclear translocation of AhR. METHODS: Four types of non-ionic surfactants were utilized to formulate niosomes by thin film hydration (TFH) method. Entrapment efficiency (EE %) of niosomes were quantified and dynamic light scattering (DLS) was performed. Transmission electron microscopy (TEM) was used to identify the morphology of LFD niosomes. Dialysis method was used to measure LFD release rate. MTS assay was adopted to examine the viability of the cells upon each treatment. The nuclear transfer of AhR was investigated by Immunocytochemistry (ICC). The mRNA expression of IL1ß and CYP1A1 were evaluated using quantitative RT-PCR. RESULTS: Span 60: cholesterol (1:1) showed the highest EE% (70.00 ± 6.24), largest particles (419.00 ± 4.16 nm) and the best uniformity with the lowest PDI (0.291 ± 0.007). TEM micrographs of Span 60 (1:1) nanoparticles showed conventional spherical vesicles with internal aqueous spaces. The release rate of LFD from Span 60 (1:1) vesicles was slower. Although the viability of LFD niosome-treated THP-1 cells was decreased, they were associated with lower cytotoxic effects compared with the free LFD counterparts. Both free and niosomal LFD treatments intensified the nuclear translocation of AhR. The mRNA expression of CYP1A1 was overexpressed while IL1ß was downregulated in both free and niosomal LFD treated combinations. CONCLUSION: LFD encapsulation in Span 60: cholesterol (1:1) niosomal formulation could be introduced as a suitable vehicle of transferring LFD to THP-1 cells, with minimal cytotoxic effects, enhancing the AhR nuclear translocation and activation and inducing immunomodulatory properties. Graphical abstract The Graphical abstract; it demonstrates the workflow of the study and summary of results in brief.

Investigation of Risk Factors Associated with Leptospirosis in the North of Iran (2011-2017).

BACKGROUND: The risk factors for infection with leptospirosis in Iran have never been studied. We aimed to determine the risk factors of leptospirosis and the epidemiological pattern of this disease in Golestan Province, Iran during 2011-2017. STUDY DESIGN: A case-control study. METHODS: This case-control study was performed on the population of patients diagnosed with leptospirosis. Controls were selected from the residents of Golestan province, northern Iran and were matched with the cases for gender, age group, and place of residence. After coding the data collected in checklists, the analysis was performed in SPSS using independent t-test, logistic regression, contingency tables, and Fisher exact test. RESULTS: Eighty-seven cases were diagnosed infected with leptospirosis. Most patients were male (69.0%) and residents of rural areas (82.7%). The three leading risk factors for leptospirosis were exposure to stagnant rice paddy water while having a skin scratch/injury (OR=11.21, 95% CI: 3.02, 43.06), washing the face with stagnant rice paddy water (OR=11.33, 95% CI: 5.12, 25.01), and sighting of rats or rat nest in rice paddies (OR=3.30, 95% CI: 1.01, 11.62). CONCLUSION: For farmers working in stagnant and muddy waters of rice paddies, occupational protection measures such as wearing waterproof boots, gloves, support, and socks can reduce the chance of infection with leptospirosis. Health education of the people with susceptible occupations about the transmission and prevention methods can also play a key role in controlling this disease.

Mutations in Hepatitis-B X-Gene Region: Chronic Hepatitis-B versus Cirrhosis.

INTRODUCTION: Specific mutations in Hepatitis-B Virus (HBV) genome would proceed the development of chronic hepatitis B to more serious consequences like cirrhosis and end-stage liver disease. AIM: This study was designed to detect deletion and insertion mutational patterns in the X-gene region in a population of chronic HBV and related cirrhosis patients. MATERIALS AND METHODS: Sixty eight chronic HBV patients and 34 HBV-related cirrhotics were recruited from the eligible cases (N=50) referred to the academic hospitals of Gorgan city, Northeast of Iran, between Jan 2011 to Dec 2013. The HBx region was amplified by semi-nested PCR using serum samples and analyzed by sequencing. RESULTS: Our findings showed deletions and insertions in the C-terminal of HBx of the cirrhotic group and 8 bp found in two chronic HBV cases (2.9%). We detected 15 types of deletions in cirrhotic cases such as 1762-1768, 1763-1770, 1769-1773 and T1771/A1775. CONCLUSION: We found that the frequencies of deletion and insertion mutations in C-terminal of X-gene were more seen in cirrhotic patients comparing to chronic HBV cases in our area of study.

Correlation Between Hepatitis B G1896A Precore Mutations and HBeAg in Chronic HBV Patients.

BACKGROUND: Hepatitis B virus (HBV) infection is an important health concern worldwide, with critical outcomes. Hepatitis B e antigen (HBeAg) negative chronic hepatitis B is frequently caused by a mutation (G1896A) in the hepatitis B virus (HBV) precore (PC) reading frame, which creates a stop codon, causing premature termination of the HBe protein. OBJECTIVES: This study aimed to investigate the G1896A PC mutation and its effect on HBeAg detection in chronic HBV patients. PATIENTS AND METHODS: In this study, 120 chronic HBV patients neither vaccinated or who had benefited from immunoglobulin therapy, were recruited. The HBV-DNA was extracted from plasma and polymerase chain reaction (PCR) was performed. Positive PCR products were subjected to automated sequencing. The HBV serological markers [hepatitis B s antigen (HBsAg), HBeAg] were tested. RESULTS: One hundred out of 120 (83.3%) patients were HBeAg negative and 100% were HBsAg positive. The comparison of nucleotide sequences with the reference sequence (Accession number: AB033559) in HBeAg negative patients showed that there was a high rate of mutations in G1896A (93.18%). CONCLUSIONS: This study indicates that the rate of G1896A mutation at the PC region among HBeAg negative patients, in the Golestan province of Iran, was similar to the average rate encountered in other parts of Iran. The PC stop codon mutation was detected in 93.18% of HBeAg negative patients. Further studies with larger sample sizes are required to elucidate the exact role of these mutations in the clinical course of chronic HBV infection.

Breast tuberculosis in northeast Iran: review of 22 cases.

BACKGROUND: Breast tuberculosis (breast TB) is an extremely rare disease, so case reviews are also rare. METHODS: This study is a retrospective review of patients with breast TB who were treated between 2002 and 2012 at the Health Center of Gorgan City. RESULTS: All 22 patients were females, their mean age was 32.4 years, and all were new cases. Patients presented with swelling of the breast (22%), lump (55%) and excretion from the involved breast (27%), and breast pain (55%). The highest rate of breast TB occurred in 2011 (27%). All patients received the DOTS regimen for a mean duration of 7.3 ± 0.7 months; in addition, segmental resection was performed on 11 patients (50%). CONCLUSIONS: The findings confirmed that breast TB in Iran should be considered as a differential diagnosis of breast masses. All patients in our study received the daily and 'Directly Observed Treatment Short-course' (DOTS) regimens. Anti-tubercular therapy for six months with or without minimal surgical intervention currently is the main treatment.