Potential role of serum vitamin D as a risk factor in pediatric acute lymphoblastic leukemia.

Vitamin D deficiency/insufficiency (VDD, VDI) is common in children yet limited experience exists on the association of VDD and hematologic malignancies amongst this population. Therefore, this study aimed to compare serum vitamin D levels in children with acute lymphoblastic leukemia (ALL) and controls. Moreover, vitamin D levels is compared in subjects with and without relapse and evaluated as a prognostic factor for relapse-free survival (RFS). Children with newly diagnosed ALL were recruited as case group. Data on demographic variables as well as the dietary habits were collected by interview. In addition, serum 25(OH)D3 was measured. The case group was followed up for 36 months to assess RFS. Overall, 358 subjects were included in the study (n = 169 cases, n = 189 controls). The mean levels of 25(OH)D3 were 28.05 ± 18.87 and 28.76 ± 12.99 in cases and controls, respectively (p = .68). VDD was found in 15.4% (n = 26) and 4.2% (n = 8) of the case and control groups, respectively (p < .001). Relapse was seen in 18.34% of patients and vitamin D levels of 20 ng/mL or above were associated with longer RFS (p = .044 by log-rank test). In this study, VDD and VDI amongst children with ALL were significantly higher than controls. In addition, lower levels of Vitamin D were associated with increased risk of relapse.

The prognostic significance of hematogones in childhood B-cell acute lymphoblastic leukemia.

BACKGROUND: Recent studies have demonstrated hematogones (HGs) expansion to be associated with favorable outcomes in hematological diseases, especially in patients with acute myeloid leukemia and patients undergoing hematopoietic stem cell transplantation. Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. As of now, minimal residual disease (MRD) remains the most compelling independent prognostic factor in childhood ALL. There is need for more prognostic tools for evaluating relapse risk. PROCEDURE: The goal of this study was to assess the prognostic value of HGs on relapse-free survival (RFS) and overall survival (OS) in childhood ALL. In this prospective cohort study, a total of 122 subjects with definitive diagnosis of precursor B lymphoblastic leukemia were evaluated. Flow cytometric HG detection was performed in bone marrow aspirates after induction and consolidation therapy. RESULTS: The median follow-up period of patients was 35.5 ± 9.4 (SD) months. Patients who had at least 1.0% HGs had a significantly better RFS (p = .023). Moreover, univariate and multivariate analyses confirmed that positive HGs were independently associated with longer RFS (unadjusted model: hazard ratio = 0.33, 95% CI = 0.12-0.91, p = .031; adjusted model: hazard ratio = 0.30, 95% CI = 0.11-0.82, p = .020). CONCLUSIONS: Along with the role of MRD, our study shows the significance of HGs as an independent prognostic factor. The results indicate the independent prognostic value of HGs on RFS after adjustment for other prognostic factors, and can be beneficial for risk stratification and treatment modifications amongst pediatric B-cell ALL patients.

Post-discharge health assessment in survivors of coronavirus disease: a time-point analysis of a prospective cohort study.

PURPOSE:  The objective of this study was to quantitatively evaluate psychological and quality of life-related complications at three months following discharge in hospitalized coronavirus disease 2019 (COVID-19) patients during the pandemic in Iran. METHODS: In this time-point analysis of prospective cohort study data, adult patients hospitalized with symptoms suggestive of COVID-19 were enrolled. Patients were stratified in analyses based on severity. The primary outcomes consisted of psychological problems and pulmonary function tests (PFTs) in the three months following discharge, with Health-related quality of life (HRQoL) as the secondary outcome. Exploratory predictors were determined for both primary and secondary outcomes. RESULTS: 283 out of 900 (30%) eligible patients were accessible for the follow-up assessment and included in the study. The mean age was 53.65 ± 13.43 years, with 68% experiencing a severe disease course. At the time of the final follow-up, participants still reported persistent symptoms, among which fatigue, shortness of breath, and cough were the most common. Based on the regression-adjusted analysis, lower levels of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio was associated with higher levels of depression (standardized ß = - 0.161 (SE = 0.042), P = 0.017) and stress levels (standardized ß =- 0.110 (SE = 0.047), P = 0.015). Furthermore, higher levels of anti-SARS-CoV-2 immunoglobulin-M (IgM) were associated with significantly lower levels of depression (standardized ß = - 0.139 (SE = 0.135), P = 0.031). CONCLUSIONS: There is an association between lung damage during COVID-19 and the reduction of pulmonary function for up to three months from acute infection in hospitalized patients. Varying degrees of anxiety, depression, stress, and low HRQoL frequently occur in patients with COVID-19. More severe lung damage and lower COVID-19 antibodies were associated with lower levels of psychological health.

Environmental Risk Factors for Pediatric Acute Leukemia: Methodology and Early Findings.

Background: Acute leukemia is the most common type of malignancy in children, and no major environmental risk factors have been identified relating to its pathogenesis. This study has been conducted with the aim for identifying risk factors associated with this disease. Methods: This study was conducted in 2016-2020 among children aged <15 years residing in Isfahan Province, Iran. Children with newly diagnosed Acute lymphoblastic leukemia, including Acute myeloid leukemia (ALL and AML) were considered a case group. The control group was selected among children hospitalized in orthopedic and surgery wards in the same region. Demographic data, parental occupational exposures and educational level, maternal obstetric history, type of feeding during infancy and parental smoking habits, exposure to pesticides, and hydrocarbons besides dietary habits (using a food frequency questionnaire) were evaluated. Results: Overall, 497 children (195 cases and 302 controls) completed the survey. In the initial analysis, there was no significant difference between case and control groups about type of milk feeding (P = 0.34) or parental age (P = 0.56); however, an association between mothers' education and increased risk for ALL was observed (P = 0.02). Conclusions: The results of this study can be helpful in better understanding the environmental risk factors involved in the incidence of acute leukemia. Future publications based on the analysis of the database created in the present study can lead to recognizing these factors. In addition, evaluating the effect of these factors on treatment outcomes is an important step in reducing the burden of the disease.

COVID-19 infection and hospitalization rate in Iranian multiple sclerosis patients: What we know by May 2021.

BACKGROUND: Despite investigations on the effect of disease modifying therapies (DMTs) used in multiple sclerosis (MS) on coronavirus disease 2019 (COVID-19); there are still controversies. OBJECTIVE: We designed this study to evaluate the epidemiological features of covid-19 in a large sample of people with MS (pwMS) in Isfahan, Iran, as well as the association between DMTs, risk of COVID-19 infection and hospitalization. METHODS: In an observational pwMS, we interviewed subjects on their MS and COVID-19 history. RESULTS: 3050 subjects were included (74% female) with a mean age of 41.36. 423 (13.8%) had confirmed COVID-19 which shows that pwMS are at a higher risk of infection compared to the general population, No significant relationship was observed in COVID-19 infection when individual drugs. Dimethyl fumarate and rituximab had the lowest and the highest relative risks for hospitalization rate compared to other drugs, respectively. CONCLUSION: We found no evidence supporting a higher prevalence of COVID-19 in pwMS compared to the general population. However, our results show pwMS to be more prone to hospitalization compared to the general population, Therefore, it is advised to use safer treatment if possible until complete vaccination, and to postpone the use of rituximab.

Safety of Sinopharm vaccine for people with Multiple Sclerosis: Study of adverse reactions and disease activity.

BACKGROUND: The aim of this study was to evaluate the safety of Sinofarm vaccine (BBIBP-CorV) in patients with multiple sclerosis (pwMS). METHODS: This study was conducted on pwMS patients in Isfahan, Iran. All participants received two doses of BBIBP-CorV (Sinopharm vaccine). Demographic information and data on vaccine side effects were collected after each dose using questionnaires. All patients that recorded worsening of MS symptoms were evaluated and those with true relapse were treated with IV methyl prednisolone. RESULTS: Of the 1538 patients, 1151 (74.8%) were female and the mean age was 40.45 ± 9.74. The average disease duration was 10.38±6.81 years and 76.1% of participants had RRMS. 92.8% of the participants were using DMTs and mean EDSS was 2.06 ± 3.16. 54.2% (833 patient) reported at least one adverse event after the first dose of vaccine and 46.8% (720 patient) after the second dose; in both cases going away in a few days. Most prevalent adverse events after both doses were injection site pain, headache, myalgia, fever and fatigue. Adverse events were more prevalent in younger and less prevalent in mildly disabled patients. There were seven cases of Covid-19 infection between the first and second vaccination dose, and eight cases during one-month follow -up after the second dose, none of whom needed mechanical ventilation. Ten patients after first dose and thirteen patients after the second dose experienced acute relapse. A patient had two relapses, one after each vaccine dose that were clinically and radiologically confirmed. The first relapse occurred seven days after the first vaccination with hemiparesis and other relapse, 14 days after the second dose with diplopia, hemiparesis and ataxia. CONCLUSION: Adverse events in pwMS following vaccination with Sinopharm vaccine was similar to the general population, which were more common in younger patients and less common in those with mild disability. As no increase in relapse rate after vaccination was detected, Sinopharm vaccine was safe in MS patients.

Familial Hypercholesterolemia (FH) in Iran: Findings from the Four-Year FH Registry.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant disease. Its diagnosis in Iran was uncommon. Iran registry of FH (IRFH) has been started from 2017 from Isfahan. In this study, we report the four-year FH registry. METHODS: The Iran FH registry is an ongoing study which is followed by a dynamic cohort. It has been started from 2017. The patients are selected from laboratories due to high cholesterol level and who have history of premature cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) criteria are used for the detection of FH. Cascade screening is performed for detection of first-degree relative of patients. RESULTS: Among the 997 individuals included in this registry, they were 522 (mean age 51.41 ± 12.91 year), 141 (mean age 51.66 ± 8.3 year), and 129 (mean age 41 ± 16.5 year) patients from laboratories, premature cardiovascular disease, and relatives, respectively. In total, 263 patients were diagnosed with probable or definite FH, and others were in the possible group. Low-density lipoprotein cholesterol (LDL) level was 141.42 ± 45.27 mg/dl in the laboratory group and 54.9% of patients were on LLT treatment. In patients with premature cardiovascular disease and FH, the LDL level was 91.93 ± 32.58 and was on LLT treatment. The LDL concentration in the first relative of FH patients was 152.88 ± 70.77 and 45.7% of them are on LLT therapy. CONCLUSIONS: Most of FH patients were underdiagnosed and undertreated before their inclusion in the IRFH. Cascade screening helps in the improvement of diagnosis.

CASCADE screening and registry of familial hypercholesterolemia in Iran: Rationale and design.

BACKGROUND: Familial hypercholesterolemia (FH) is one of the most common genetic disorders, which leads to premature coronary artery disease (CAD). It has been suggested that heterozygous FH affects around 1:250 to 1:500 in the general population or even more than this, and homozygous FH affects 1:1000000 of the population. If patients with FH are not diagnosed and treated early in life, many of them will develop premature CAD event. As most of the patients with FH are undiagnosed, it is recommended that the general population be screened for high risks of the events since early treatments can reduce the risk of premature CADs. The clinical diagnostic criteria for FH consist of increased plasma low-density lipoprotein cholesterol (LDL-C), clinical features and family history of CAD. However, deoxyribonucleic acid (DNA)-based detection of FH mutation has high diagnostic values. As there was no screening for FH in Iran up until now, we have started screening and registering patients with FH using the CASCADE method. METHODS: We detected FH subjects in the general population by screening laboratories according to their high LDL-C levels (more than 190 mg/dl or 150 mg/dl if receiving treatments), while our second approach was hospital-based in which one screens hospitalized patients with premature CAD events. RESULTS: We intended to screen families of indexed patients to provide standard care and therapy in order to optimize their LDL-C. CONCLUSION: This article provides detailed information on the rationale and design of this screening and registry in Iran.