Fulminant coronavirus disease 2019 meningitis in Iranian infants: a case series.

BACKGROUND: Pediatric coronavirus disease 2019 infection usually presents with respiratory and gastrointestinal symptoms. In this report we present fulminant meningitis as the main presentation of coronavirus disease 2019 without major signs and symptoms of other organs' involvement in 3 infants. CASES: The first case was a 4 months Iranian male infant with fulminant meningitis as the main presentation of coronavirus disease 2019 without other organ involvement. He was treated as suspected bacterial meningitis but CSF PCR and CSF culture were negative for common meningeal pathogens. On 3rd day, his coronavirus disease 2019 PCR test became positive, while it was negative on 1st day. The second case was a 13 months Iranian male infant with fever, irritability, and photophobia for 24 h before poorly controlled status epilepticus. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. Seizures were controlled with multiple anti-seizure medications. The third case was a 14 months Iranian female infant with fever and seizure1 hour before admission, leading to poorly controlled status epilepticus despite anti-epileptic therapy 10 h after admission. CSF coronavirus disease 2019 PCR became positive while CSF PCR and CSF culture were negative for other common meningeal pathogens. He was controlled with multiple anti-seizure medications. CONCLUSION: Meningitis of coronavirus disease 2019 should be considered in severely ill pediatric cases with poorly controlled seizures and RBC in CSF smear. Also, pediatricians can consider corticosteroids, remdesivir, and IVIG therapy in these cases.

Association of body mass index with COVID-19 outcome in a pediatric tertiary referral hospital in Iran.

BACKGROUND: One of the challenging risk factors for severe COVID-19 infection is obesity and high body mass index (BMI). In this study we assessed the association between BMI and outcomes of hospitalized pediatric patients with COVID-19 in Iran. METHOD: This retrospective cross-sectional study was performed in the biggest referral pediatric hospital in Tehran from March 7 to August 17, 2020. All hospitalized children ≺18 years of age with laboratory-confirmed COVID-19 were included in the study. We evaluated the association of BMI with COVID-19 outcomes (death, severity of clinical course, oxygen therapy, intensive care unit [ICU] admission, ventilator requirement). The secondary objectives were investigating the association of gender, underlying comorbidity, and patient age with COVID-19 outcomes. The limits for obesity, overweight, and underweight were set at BMI >95 percentile, 85≤ BMI ≤ 95, and BMI<5 percentile, respectively. RESULTS: In total, 189 confirmed pediatric cases of COVID-19 (0.1-17 years) with a mean age of 6.4 ± 4.7 years were included. Overall, 18.5% of the patients were obese and 33% were underweight. We found that BMI had no significant relation with COVID outcomes in pediatric cases but after subgrouping the participants, underlying comorbidities and lower BMI in previously ill children were independently associated with a poor clinical outcome of COVID-19. In addition, the previously ill children with higher BMI percentiles were at a relatively lower risk of ICU admission (95% CI: 0.971-0.998, OR: 0.98, p = 0.025) and better clinical course of COVID-19 (95% CI: 0.970-0.996, OR: 0.98, p = 0.009). The BMI percentile had a statistically significant direct relationship with age (Spearman correlation coefficient= 0.26, p<0.001). When we separated the children with underlying comorbidity, the BMI percentile was significantly lower (p<0.001) in comparison to the previously healthy children. CONCLUSION: Based on our results, obesity is not related to COVID-19 outcomes in pediatric patients, but after controlling for confounding effects, underweight in children with underlying comorbidities was more likely to be associated with a poor prognosis of COVID-19.

Estrogen replacement therapy: effects of starting age on final height of girls with chronic kidney disease and short stature.

INTRODUCTION: We investigated the age of starting Estrogen replacement therapy as a key parameter for reaching near normal Final Height (FH) in Chronic Kidney Disease (CKD) girls with growth retardation. METHOD: This open label, quasi-experimental designed and matched controlled clinical trial was performed on CKD girls with short stature and later onset of puberty or delayed puberty according to clinical and laboratory investigations. Participants of group 1 and 2 had been treated with Growth Hormone (GH), and Ethinyl Estradiol (EE). EE was administered from 11 and 13 yrs. old in groups 1 and 2 respectively. Group 3 was selected from patients that did not accept to start GH or EE till 15 years old. The effect of the age of starting EE on FH, GH therapy outcomes, bone density, and calcium profile were evaluated. RESULT: Overall, 16, 22, and 21 patients were analyzed in groups 1, 2, and 3 respectively. Mean Mid-Parental Height (MPH) had no significant difference between the 3 groups. GH therapy significantly enhanced mean FH in groups 1 and 2 in comparison with group 3 (ß = - 4.29, p < 0.001). Also, multivariable backward linear regression illustrated significant negative association between FH and age of starting EE (ß = 0.26, p < 0.001). Mean Para Thyroid Hormone (PTH), mean femoral and lumbar bone density were significantly enhanced after GH and EE therapy (p value: < 0.001). CONCLUSION: We recommend starting EE from 11 yrs. old in CKD short stature girls who have no clinical and laboratory sign of sexual maturity at 11 yrs. to enhance the cost effectiveness of GH therapy.

Investigating the safety and efficacy of hematopoietic and mesenchymal stem cell transplantation for treatment of T1DM: a systematic review and meta-analysis.

BACKGROUND: Stem cell transplantation (SCT) has paved the way for treatment of autoimmune diseases. SCT has been investigated in type 1 diabetes mellitus (T1DM) as an autoimmune-based disorder, but previous studies have not presented a comprehensive view of its effect on treatment of T1DM. METHODOLOGY: After registration of the present systematic review and meta-analysis in the PROSPERO, a search was done according to the Cochrane guidelines for evaluation of clinical trials to find eligible clinical trials that investigated the effect of SCT on T1DM (based on ADA® diagnostic criteria) from PubMed, Web of science, Scopus, etc, as well as registries of clinical trials from January 1, 2000, to September 31, 2019. A search strategy was designed using MeSH and EM-tree terms. Primary outcome included the changes in the insulin total daily dose (TDD) (U/kg) level, and secondary outcomes included the changes in the HbA1c, c-peptide, and adjusted HbA1c levels. The Q Cochrane test and I2 statistic were performed to assess the heterogeneity and its severity in primary clinical trials. The Cochrane ROB was used to determine risk of bias, and Cochrane Handbook for Systematic Reviews of Interventions was used in the full text papers. The meta-analysis was accomplished in the STATA software, and the results were shown on their forest plots. Confounders were evaluated by the meta-regression test. RESULTS: A total of 9452 studies were electronically screened, and 35 papers were included for data extraction. The results of this review study showed that 173 (26.5%) diabetic patients experienced insulin-free period (from 1 to 80 months), and 445 (68%) showed reduction in TDD of insulin after the SCT. Combination of hematopoietic stem cell (HSC) with mesenchymal stem cell (MSC) transplantation were significantly associated with improvement of the TDD (SMD: - 0.586, 95% CI: - 1.204/- 0.509, I2: 0%), HbA1c (SMD: - 0.736, 95% CI: - 1.107/- 0.365, I2: 0%), adjusted HbA1c (SMD: - 2.041, 95% CI: - 2.648/- 1.434, I2: 38.4%), and c-peptide (SMD: 1.917, 95% CI: 0.192/3.641, I2: 92.5%) on month 3 of follow-up, while its association had a growing trend from 3 to 12 months after the transplantation. Considering severe adverse events, HSC transplantation accompanied with conditioning could not be suggested as a safe treatment. CONCLUSION: Most of the clinical trials of SCT in T1DM were single arm. Although meta-analysis illustrated the SCT is associated with T1DM improvement, well-designed randomized clinical trials are needed to clarify its efficacy. RECOMMENDATION: Based on the results of this meta-analysis, the MSC and its combination with HSC could be considered as "Safe Cell" for SCT in T1DM. Furthermore, to evaluate the SCT efficacy, calculation of insulin TDD (U/kg/day), AUC of c-peptide, and adjusted HbA1c are highly recommended.

Acute and sub-acute ocular manifestations in pediatric patients with COVID-19: A systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been the most challenging health problem in the last 2 years. Post-COVID-19 multisystem inflammatory syndrome of children (MIS-C) is a severe post-COVID-19 complication in pediatric patients. Ocular manifestations may be the first presentation of MIS-C, wherein prompt treatment may improve outcomes. In this systematic review, we aimed to summarize the acute and sub-acute ocular manifestations in pediatric patients with laboratory-confirmed COVID-19. Methods: We included all online primary studies, with no language restriction and published between January 1, 2019 and November 18, 2020, reporting any acute or sub-acute ocular manifestations in children with laboratory-confirmed COVID-19. PubMed/MEDLINE was searched using the following MeSH and Emtree terms: "eye," "ophthalmologic," "ocular," "vision," "conjunctivitis," "severe acute respiratory syndrome coronavirus 2," "SARS-CoV-2," "corona," "2019-nCoV," "COVID19," and "COVID." The eligibility and quality of the selected records were assessed by two independent reviewers as per the Cochrane Handbook for Systematic Review. Results: A total of 1,192 records were identified electronically. Seven papers were extracted from the reference lists of the eligible records. Thirty-six papers met the inclusion criteria and were categorized into two subgroups according to acute or sub-acute presentation of ocular manifestations. Among 463 pediatric patients with COVID-19, 72 (15.5%) had acute ocular manifestations. There was one patient with central retinal vein occlusion and another with photophobia and diplopia associated with meningoencephalitis. Among 895 pediatric patients with post-COVID-19 MIS-C, 469 (52.4%) had ocular manifestations, which only included non-purulent conjunctivitis. Conclusions: Ocular manifestations have been reported in less than one-fifth of pediatric patients with acute COVID-19. Furthermore, conjunctivitis was the only ocular manifestation reported in half of the patients with MIS-C, and it may be missed easily due to its non-purulent nature. During the COVID-19 pandemic, pediatricians and health workers must remain vigilant for early detection of signs of this potentially fatal post-COVID-19 inflammatory syndrome.

Red flags of poor prognosis in pediatric cases of COVID-19: the first 6610 hospitalized children in Iran.

INTRODUCTION: COVID-19 clinical course, effective therapeutic regimen, and poor prognosis risk factors in pediatric cases are still under investigation and no approved vaccinehas been introduced for them. METHODS: This cross-sectional study evaluated different aspect of COVID-19 infection in hospitalized COVID-19 positive children (≺18 years oldwith laboratory confirmed COVID-19 infection, using the national COVID-19 registry for all admitted COVID-19 positive cases from February 19 until November 13,2020, in Iran. RESULTS: We evaluated 6610 hospitalized children. Fifty-four percent (3268) were male and one third of them were infants younger than 1 year. Mortality rate in total hospitalized children was 5.3% and in children with underlying co-morbidities (14.4%) was significantly higher (OR: 3.6 [2.7-4.7]). Chronic kidney disease (OR: 3.42 [1.75-6.67]), Cardiovascular diseases (OR: 3.2 [2.09-5.11]), chronic pulmonary diseases (OR: 3.21 [1.59-6.47]), and diabetes mellitus (OR: 2.5 [1.38-4.55]), resulted in higher mortality rates in hospitalized COVID-19 children. Fever (41%), cough (36%), and dyspnea (27%) were the most frequent symptoms in hospitalized children and dyspnea was associated with near three times higher mortality rate among children with COVID-19 infection (OR: 2.65 [2.13-3.29]). CONCLUSION: Iran has relatively high COVID-19 mortality in hospitalized children. Pediatricians should consider children presenting with dyspnea, infants≺ 1 year and children with underlying co-morbidities, as high-risk groups for hospitalization, ICU admission, and death.

Does the reaction size of skin prick test associated with the allergic rhinitis symptom severity?

BACKGROUND: Skin prick test (SPT) has the best positive predictive value to diagnose respiratory atopic diseases, including allergic rhinitis (AR), but the association of severity of allergic symptom and SPT reaction size has not been clearly determined yet. METHODS: In this a cross- sectional investigation, the severity of disease is classified using a visual analog scale for main symptoms, and SPT was conducted according to the principles of the European Academy of Allergy and Clinical Immunology. RESULTS: Thirty seven percent of the participants had at least one severe symptom. Patients with sensitivity to Alternaria (common allergens in humans) or tree pollens had more severe symptoms. We found that in patients who had sensitivity to Russian thistle pollen, wheal size >6 mm, was associated with more severe symptoms. CONCLUSION: Despite previous conflicts to rely on SPT test for starting immunotherapy, we recommend this test especially for patients sensitive to Alternaria, weed pollens, and tree pollens, considering the size of wheal in association with AR symptom severity.

Novel Treatment for Congenital Disorder of Glycosylation in a Patient with Novel Homozygote Mutation of PMM2: A Case Report and Review Literature.

BACKGROUND: In Congenital Disorder of Glycosylation (CDG) type Ia, homozygous mutations of the PMM2 gene cause phosphomannomutase 2 dysfunction. CASE PRESENTATION: Herein, a 10-month-old girl, is presented with severe hypotonia, along with inappropriately normal mental status and normal facies. High 2-ketoglutaric acid was detected in her urine, therefore, the diagnosis of 2-Ketoglutarate dehydrogenase complex (KDHC) deficiency was made for this patient. A high dose of vitamin B1 was administered because thiamine is considered a co-factor in this inborn error of metabolism. She responded very well to the daily administration of 500 mg/day vitamin B1 and stood up without help 5 months later. She had also experienced a seizure, which responded well to pyridoxine. Then, she grew up into a 3.5-years-old child who could talk and walk normally. Recently, whole-exome sequencing was performed for her, which showed homozygote mutation of PMM2, therefore, the diagnosis was changed from KDHC deficiency to PMM2-CDG. CONCLUSION: Paying attention to the pathophysiology of inborn errors of metabolism is necessary while considering the defective enzyme co-factor, which may help us to find an option for the treatment of such rare diseases.

Sulfur Mustard and Immunology; Trends of 20 Years Research in the Web of Science Core Collection: A Scientometric Review.

BACKGROUND: We aimed to use the scientometric approach to evaluate immunological studies on the subject of sulfur mustard over the past 20 years. METHODS: In this scientometric study, the Web of Science Core Collection was searched on the studies about sulfur mustard. The published papers related to the field of immunology were retrieved from these papers. HistCite software and VOSviewer were the applied software packages for bibliometric analysis, information visualization, and creating bibliometric networks. RESULTS: Over the past 20 years, 741 researchers from 22 countries have published 201 scientific papers in 95 journals. Iran and the United States with 93 and 68 published articles ranked at the top. The Journal of International Immunopharmacology, with 33 published papers, 439 Total Global Citation Score (TGCS), and 105 Total Local Citation Score (TLCS) was the most productive and most influential in this regard. The paper entitled "Biomonitoring of exposure to chemical warfare agents: A review" and another paper entitled "Sardasht-Iran Cohort Study of Chemical Warfare Victims: Design and Methods" were the most influential papers in this topic with 200 TGCS and 27 TLCS, respectively. The most productive and the most influential centers were "Immunoregulation Research Center of Shahed University" and "The Janbazan Medical and Engineering Research Center (JMERC)," respectively. CONCLUSION: The result of our report as the unique scientometric evaluation of the research on sulfur mustard and Immunology can be used as a roadmap for authors, researchers, and policymakers to define the best ways to allocate their financial and executive resources.

Safety and efficacy of hematopoietic and mesanchymal stem cell therapy for treatment of T1DM: a systematic review and meta-analysis protocol.

INTRODUCTION: Insulin standard treatment of T1DM cannot cure the patients as different chronic complications occurred subsequently. Investigations on a curative treatment in T1DM propose cell replacement or maintenance instead of exogenous insulin therapy, but different dimensions of this novel treatment are not clarified. METHODS AND ANALYSIS: We will include all clinical trials which have evaluated the efficacy MSC or HSC transplantation in T1DM treatment; electronically search bibliographic databases, country registration data banks, and gray literatures; and hand-search two key journals, two experts' article, and references of the included articles with no language restriction. Primary outcome is the extent of reduction in insulin requirement and secondary outcomes are safety of MSC and HSC therapy, effect of this therapy on diabetic parameters, effect of the rout of transplantation and origin of the MSC or HSC on efficacy of treatment, studies heterogeneity and potential reasons of it. Heterogeneity and its severity will be calculated with Q Cochrane test, P value, and I2 index. STATA software version 12 will be used for meta-analysis. PROSPERO Registration number: CRD42016047176. ETHICS AND DISSEMINATION: We will publish the systematic review in a peer review journal; as it presents an analysis of published literature, the study does not require ethical approval. STRENGTHS AND LIMITATIONS OF THIS STUDY: This systematic review and meta-analysis will investigate the efficacy of MSC and HSC transplantation in T1DM treatment with no language restriction. Also we will evaluate gray literatures after hand searching. This protocol is prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Two reviewers will evaluate screened full texts, extract data, and asses risk of bias of eligible primary studies independently. As there is the possibility that we miss some unpublished primary studies due to negative results, we will use funnel plot to detect this and correct it with fill and trim method.