Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with "Inhibitor" formation.

BACKGROUND: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+IgD-CD27+/non-class-switched CD19+IgD+CD27+ memory B cell subsets and CD19+CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. METHODS: This cross-sectional case-control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. RESULTS: The frequency of CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+IgD-CD27+ class-switched and CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. CONCLUSION: This study is the first to demonstrate a dysregulated proportion of CD19+IgD+CD27+ non-class-switched memory B cells and CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

Iron Overload in Children With Leukemia; Identification of a Cutoff Value for Serum Ferritin Level.

OBJECTIVE: To determine the prevalence of iron overload in children with acute lymphoblastic leukemia (ALL) after treatment cessation and establish a cutoff value for serum ferritin level as an indicator of iron overload. BACKGROUND: Early detection and monitoring of iron overload in patients with leukemia is crucial. METHODS: In this prospective cohort study, 66 pediatric patients with ALL who were treated at a tertiary referral center affiliated with Shiraz University of Medical Sciences in Shiraz, Southern Iran, were investigated from July 2020 to December 2022. Serum ferritin levels were measured 6 months after treatment completion. T2* magnetic resonance imaging of the liver and heart was done for all patients. The receiver operating characteristic curve was used to illustrate the area under the receiver operating characteristic curve to assess the diagnostic value of serum ferritin level and total transfusion volume. RESULTS: A total of 24 patients (36.4%) had iron overload in the heart or liver based on T2 magnetic resonance imaging findings. Serum ferritin level was a highly accurate diagnostic marker for iron overload in pediatric patients with ALL, with a sensitivity of 95.8%, and specificity of 85.7% for a cutoff value of 238.5 ng/mL. Also, blood transfusion was a good predictor of iron overload a sensitivity of 75% and specificity of 81% for a cutoff value of 28.3 mL/kg. CONCLUSION: We identified specific cutoff values for serum ferritin and blood transfusion volume to predict iron overload with high sensitivity and specificity. These markers offer a cost-effective and accessible approach for periodic screening of iron deposition, particularly in resource-constrained settings.

The Prevalence of Obstructive Sleep Apnea and Associated Symptoms among Patients with Sickle Cell Disease: A Systematic Review and Meta-analysis.

Previous studies have shown that patients with sickle cell disease (SCD) are at high risk for obstructive sleep apnea (OSA). In the current study, we aimed to systematically review the literature to address the prevalence of OSA and associated symptoms among patients with SCD. Electronic databases, including Web of Science, Scopus, PubMed, Google Scholar, and Embase were systematically searched to identify the relevant original articles on patients with SCD. Newcastle Ottawa scale was used for quality assessment. Data were pooled by using random effects models. Subgroup analyses were performed by age groups. Thirty-nine studies containing details of 299,358 patients with SCD were included. The pooled results showed that more than half of these patients had OSA with different severities. The prevalence rates of OSA among children with apnea hypopnea index (AHI) cutoffs of above 1, 1.5, and 5 were 51% (95% confidence interval (CI) 36-67%), 29% (95% CI 19-40%), and 18% (95% CI 14-23%), respectively. The prevalence of OSA among adults with AHI cutoff of 5 was 43% (95% CI 21-64%). The pooled rates of snoring, nocturnal enuresis, nocturnal desaturation, and daytime sleepiness were 55% (95% CI 42-69%), 37% (95% CI 33-41%), 49% (95% CI 26-72%), and 21% (95% CI 12-30%), respectively. Given the high prevalence of OSA in patients with SCD, probable greater burden of SCD complications, and irreversible consequences of OSA, screening for OSA symptoms and signs seems useful in these patients. By screening and identifying this heterogeneous disorder earlier, available treatment modalities can be individualized for each patient.

The efficacy of Allium ampeloprasum L. in reducing neutrophil recovery time in childhood cancer with febrile neutropenia: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Febrile neutropenia is a serious complication of cancer chemotherapy that can result in delays in treatment. This study evaluates the efficacy of A. ampeloprasum L. at neutrophil recovery time in children with chemotherapy-associated febrile neutropenia. METHODS: This single-center, parallel-group, double-blind, randomized clinical trial was conducted at an oncology hospital. Patients selected among childhood cancers with febrile neutropenia. Overall, 97 febrile neutropenic children were enrolled. The intervention group (n=49) was given A. ampeloprasum L. in capsules (500 mg twice daily) for seven days plus supportive care. The control group (n=48) was treated similarly with supportive care and placebo capsules. Total white blood cell (WBC) and absolute neutrophil counts (ANC) were checked daily and neutrophil recovery time in both groups was compared. RESULTS: Patients in the intervention group experienced shorter neutrophil recovery compared to the control group (4.02 ± 2.32 days vs. 6.38 ± 2.80 days, respectively, P less than 0.001). The intervention group was discharged from the hospital earlier than the control group with a mean of two days, but it did not reach statistical significance (P=0.133). Mean WBC and ANC were not significantly different in the two groups. Herbal medicine was well tolerated, and no adverse effect was reported. CONCLUSIONS: A fresh, lyophilized extract from deciduous leaves of A. ampeloprasum L. can effectively shorten the ANC recovery time leading to an earlier release from the hospital. The trial was registered in the Iranian Registry of Clinical Trials with registration No. IRCT2015051615666N2 (http://www.irct.ir/).

Investigating the trends of incidence rates of breast cancer in Southern Iran: a population based survey.

BACKGROUND: The overall incidence of breast cancer is different all over the world and even within a nation. The present study aims to investigate the stratum-specific incidence trends of breast cancer in southern Iran. METHODS: In this retrospective cohort study, the data of Fars Population-Based Cancer Registry was used during 2001-2018. New cancer cases with ICD-O-3 codes C50.0 to C50.9 were categorized based on age group, morphology, and topography. Age-specific incidence rates of breast cancer were calculated during 2001-2018. Annual overall and truncated age-standardized incidence rates and their 95% Confidence Intervals (CIs) were also calculated. Afterward, the Annual Percentage Changes (APCs) of the age-specific and age-standardized incidence rates of breast cancer during 2001-2018 were calculated using Joinpoint regression software. RESULTS: An increasing trend was observed in the incidence of breast cancer among women during 2001-2018 (APC of age-standardized incidence rates: 9.5 (95% CI: 7.5, 11.5)).However, the trend was increasing less during the recent years. The APC of age-standardized rates decreased from 15.03 (95% CI: 10.4, 19.8) in 2007 to 6.15(95% CI: 4.0, 8.4) in 2018. The most common morphology of breast cancer was invasive ductal carcinoma (77.3% in females and 75.1% in males) and its trend was similar to the general trend of different types of breast cancer. The most common site of breast cancer was the upper outer quadrant. Most breast cancer cases were female and males accounted for 2.45% of the cases. Among females, 40-55 was the most prevalent age group. CONCLUSION: The incidence of breast cancer among women living in southern Iran showed an increasing trend from 2001 to 2018. However, the rate of increase exhibited a milder slope during the more recent years. Based on the higher prevalence of breast cancer in the 40-55 age group observed in the present study, it offers valuable insight into the potential reduction of the breast cancer screening age from 50 to 40 years for healthy Iranian women. However, before implementing such a policy change, it is crucial to conduct additional studies that specifically examine the cost-effectiveness, as well as the potential benefits and risks associated with this alteration.

Skeletal complications in patients with hemophilia: a single-center experience.

BACKGROUND: Arthropathy is a common complication in patients with hemophilia. We examined the prevalence of this skeletal complication in patients with hemophilia who were registered at a Comprehensive Hemophilia Center in Shiraz, Southern Iran. MATERIALS AND METHODS: In this cross-sectional study, an orthopedic specialist visited 448 patients and conducted screenings for skeletal complications. The assessment included evaluating the type of hemophilia, disease severity, treatment modality, the presence of inhibitors, and the identification of skeletal complications. RESULTS: Ninety patients with hemophilia A, with a mean age (SD) of 31.6 (14.4) years, and 10 patients with hemophilia B, with a mean age of 30.5 (20.6) years, were assessed. The most frequently affected joints were the knee and ankle joints. In the univariate analysis, patients with severe disease were more likely to exhibit synovitis, a target joint, and bone disease compared to patients with non-severe disease. Additionally, a history of treated or active hepatitis and an annual bleeding rate showed significant associations with the target joint. In the multivariable logistic regression analysis, disease severity (OR 14.43, 95% CI 1.6-129.6) and a higher age at diagnosis (OR 1.06, 95% CI 1.00-1.13) increased the likelihood of developing osteoporosis. A history of hepatitis (OR 3.67, 95% CI 1.28-10.48) was identified as an independent risk factor for the target joint. CONCLUSION: Skeletal complications are a common occurrence in hemophilia. Regular consultations with orthopedic specialists, focusing on bleeding control and hepatitis prevention, are essential for reducing the impact of this debilitating complication.

The impact of inhibitors on the quality of life in patients with hemophilia.

Objective: To investigate the association of health-related quality of life in hemophilia patients with inhibitor and clinical and demographic characteristics. Methods: In this multi-center cross-sectional study, 41 male patients with hemophilia A were investigated from May to October 2021. All patients were registered at the Hemophilia Clinic affiliated with Shiraz and Zahedan Universities of Medical Sciences in Iran. Health-related quality of life of the patients was evaluated by the Short Form-36 questionnaire. Results: The patients' mean ± SD of age was 36.9 ± 13.2 (range: 18-76) years. Eleven patients (26.8%) were inhibitor positive. In univariate analysis, physical function, mental health dimension, and total Short Form-36 scores were significantly lower in the inhibitor-positive patients (p < 0.001, p = 0.045, and p = 0.035, respectively). Moreover, patients with severe disease showed significantly lower scores in physical function (p < 0.001), physical health dimension (p = 0.018), and total Short Form-36 (p = 0.031) than those with mild and moderate hemophilia. Also, blood-borne infections showed a significant association with lower score in physical health dimension (p = 0.038). In addition, annual bleeding rate showed significant negative correlations with physical health dimension (rs = -0.609, p < 0.001), mental health dimension (r = -0.317, p = 0.044), and total Short Form-36 (r = -0.455, p = 0.003) scores. In multiple linear regression analysis, disease severity revealed a significant negative relationship with scores in physical function (p = 0.001), role physical (RP) (p = 0.015), general health (GH) (p = 0.006), physical health dimension (p = 0.006), and marginally in total Short Form-36 score (p = 0.054). Also, age of the patients showed a significant negative association with physical function and GH scores (p < 0.001 and p = 0.015, respectively). Conclusion: Disease severity and age were shown as independent factors affecting health-related quality of life, but inhibitor alone was not an independent influencing factor. Reduced health-related quality of life was also observed in hemophilia patients with higher annual bleeding rate and blood-borne infections. Therefore, it is necessary to pay more attention to these subgroups. Further studies with larger sample size are needed for more accurate results.

Correlation of Serum Ferritin Level with Heart T2 MRI in Transfusion Dependent Thalassemia: a Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac complications in patients with transfusion-dependent thalassemia (TDT) are one of the major causes of mortality in these patients which annually impose economic burden on the endemic countries. Heart T2 MRI is a good modality for evaluating iron overload. Our aim was to investigate the pooled correlation between the serum ferritin level and heart iron overload in TDT patients and compare the effect size in different geographical areas. METHODS: PRISMA checklist was used to summarize the literature search. Three major databases were used for the papers and exported into endnote for screening. Data were extracted into an Excel spreadsheet. The data were analyzed using STATA software. CC was considered as the effect size, and the amount of heterogeneity was indicated by I-squared. Meta-regression was used for age. Also, sensitivity analysis was performed. RESULTS: The present study showed a statistically significant negative correlation of the serum ferritin level with heart T2 MRI: -0.30 (95% CI -0.34, -25). This correlation was not significantly affected by the patients' age (p-value: 0.874). Given different geographic area, most of the studies from different countries indicated that the correlation between the serum ferritin and heart T2 MRI was statistically significant. CONCLUSIONS: The pooled analysis showed a significant negative moderate correlation between the serum ferritin level and heart T2 MRI in patients with TDT, regardless of their age. This issue underscores the importance of periodical evaluation of serum ferritin level in patients with TDT in developing countries with low financial supports and limited resources. Further studies are suggested to evaluate the pooled correlation of the serum ferritin level with iron concentration of other vital organs.

Risk Factors for the Occurrence of Asymptomatic Brain Lesions in Patients with ß-Thalassemia: a Systematic Review and Meta-Analysis.

BACKGROUND: Several factors, including increased platelet aggregation, decreased platelet survival, decreased antithrombotic factors cause a hypercoagulable state in thalassemia patients. This is the first meta-analysis designed to summarize the association of age, splenectomy, gender, and serum ferritin and hemoglobin levels with the occurrence of asymptomatic brain lesions in thalassemia patients using MRI. METHODS: This systematic review and meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. We searched four major databases and included eight articles for this review. The quality of the included studies was assessed based on the Newcastle-Ottawa Scale checklist. Meta-analysis was performed using STATA 13. Odds ratio (OR) and standardized mean difference (SMD) were considered as effect sizes for comparing the categorical and continuous variables, respectively. RESULTS: The pooled OR for splenectomy in patients with brain lesions compared to those without lesions was 2.25 (95% CI 1.22 - 4.17, p = 0.01). The pooled analysis for SMD of age between patients with/without brain lesions was statistically significant, 0.4 (95% CI 0.07 - 0.73, p = 0.017). The pooled OR for the occurrence of silent brain lesions was not statistically significant in males compared to females, 1.08 (95% CI 0.62 - 1.87, p = 0.784). The pooled SMD of Hb and serum ferritin in positive brain lesions compared to negatives were 0.01 (95% CI -0.28, 0.35, p = 0.939) and 0.03 (95% CI -0.28, 0.22, p = 0.817), respectively, which were not statistically significant. CONCLUSIONS: Older age and splenectomy are risk factors for developing asymptomatic brain lesions in ß-thalassemia patients. Physicians should consider a careful assessment of high-risk patients for starting prophylactic treatment.

The survival of childhood leukemia: An 8-year single-center experience.

BACKGROUND: The survival of childhood leukemia has improved. We aimed to report the survival rate and the associated factors in children with acute leukemia during an 8-year follow-up. AIMS: This study investigates the 8-year survival rates of children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in Shiraz, the largest oncology center in Southern Iran. We also aimed to assess the independent factors associated with higher mortality in childhood leukemia. METHODS: Children 0-18 years with acute leukemia were followed from 2013 to 2021 in Shiraz, Iran. The 8-year overall survival (OS) and event-free survival (EFS) rates were estimated by the Kaplan-Meier method. Independent factors associated with survival were assessed by the Cox regression hazard modeling. RESULTS: We included 786 children, with 43.5% female, and a mean age of 6.32 ± 4.62 years. Patients with AML compared to ALL experienced more relapse (34.6% vs. 22.5%, p = .01) and death (31.7% vs. 11.3%, p < .001). The cumulative 8-year OS and EFS were 81% (95% confidence interval (CI), 74.3% to 86.1%) and 68.3% (95% CI, 63.5% to 72.7%) in ALL patients and 63.5% (95% CI, 52.1% to 72.9%) and 43% (95% CI, 33.1% to 52.6%) in AML patients. Multivariable analysis revealed that hepatomegaly (hazard ratio = 4, 95% CI, 1.0 to 22.3, p = .05) was the main independent risk factor of death in ALL patients. No definite risk factor was defined for AML patients. CONCLUSION: The survival of childhood leukemia has recently increased dramatically in low-middle income countries. Hepatomegaly was introduced as a potential risk factor for lower survival in ALL patients. Further multicenter studies are needed to confirm the validity of this association.

Thromboprophylaxis Outcome in Childhood SARS-CoV-2 Infection: A Single-Center Experience.

BACKGROUND: The SARS-CoV-2 infection has been associated with potentially endothelial damage and coagulation cascade activation that cause thrombosis. There is limited information on thrombosis and anticoagulant therapy in children with coronavirus disease 2019 (COVID-19). AIMS: This study evaluates the outcome of thromboprophylaxis in children younger than 18-year old with COVID-19 infection. METHODS: A retrospective study was conducted on 184 hospitalized pediatric patients with confirmed COVID-19 infection. A designed questionnaire was made to collect all demographic, clinical, and laboratory data. According to World Health Organization, the patients were classified as asymptomatic/mild, moderate, severe, and critically ill. RESULTS: The mean age of the patients was 7.04±5.9 (1 wk to younger than 18 y). Overall, 33 patients received anticoagulant therapy. All patients who passed away (n=19) belonged to the critical group. One patient (1.28%) was complicated with deep vein thrombosis despite taking thromboprophylaxis, and 1 (1.28%) with pulmonary thromboembolism while the patient did not take an anticoagulant. CONCLUSIONS: Our data showed a lower rate of thrombosis (1.4%) than adult patients with COVID-19. It may underline the role of anticoagulants in moderate to severe/critically ill children with COVID-19 infection. Expert opinion and personal experience are necessary, while we have a significant knowledge gap in understanding COVID-19-associated coagulopathy and thrombotic risk in children.

Cytokine Levels in Patients with ß-Thalassemia Major and Healthy Individuals: a Systematic Review and Meta-Analysis.

BACKGROUND: Cytokine levels in patients with ß-thalassemia major (ß-TM) have been assessed in several studies. Accordingly, a wide variety of immune disturbances has been shown in patients with thalassemia. Recurrent transfusions cause iron overload, which induces an increase in the production of cytokines. However, no systematic approach or meta-analysis has been done to provide a clear feature of cytokine levels in ß-TM. The present meta-analysis aimed to summarize the existing evidence regarding different levels of cytokines in patients with Β-TM compared to healthy controls. METHODS: This study was performed according to the PRISMA checklist. A systematic search was done in Web of Science (ISI), Scopus, and PubMed databases. The quality of the included studies was assessed based on the New-castle-Ottawa Scale. Meta-analysis was run via STATA 13 software. The standardized mean difference was considered the effect size for comparing the continuous variables. RESULTS: This meta-analysis included 16 studies conducted on 805 ß-TM patients and 624 healthy individuals (with the mean age of 16.10 ± 4.33 and 16.22 ± 3.78, respectively). The results showed significantly higher levels of Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and IL-10 in patients with ß-TM compared to the healthy controls. CONCLUSION: The results indicated that the levels of both inflammatory and anti-inflammatory cytokines were higher in patients with ß-TM compared to the healthy population, which could be associated with higher levels of oxidative markers in these patients. Further studies are suggested to evaluate the difference in cytokine levels among different types of thalassemia.

Optical coherence tomography findings in patients with transfusion-dependent ß-thalassemia.

BACKGROUND: Structural ophthalmologic findings have been reported in patients with ß-thalassemia due to chronic anemia, iron overload, and iron chelation therapy toxicity in few previous studies. We aimed to investigate structural ocular findings and their relationship with hematological parameters in patients with transfusion-dependent ß-thalassemia (TDT). METHODS: In this cross-sectional study, from January 2018 to January 2019, 39 patients with TDT over the age of 18 participated. Multicolor fundus imaging, optical coherence tomography (OCT), and blue light fundus autofluorescence imaging were performed for all patients and 27 age- and sex-matched controls. RESULTS: The mean age of patients was 28.6 ± 6.2 years. The central macular thickness and macular thicknesses in all quadrants were significantly thinner in patients than controls (P<0.05). None of the retinal nerve fiber layer (RNFL) measurements were significantly different between TDT patients and controls. There was a significantly negative correlation between hemoglobin with central macula thickness (r=-0.439, P=0.005). All measurements of macular subfield thickness were insignificantly thinner in patients with diabetes mellitus (DM) compared to the non-DM subgroup. CONCLUSIONS: Macular thickness was significantly thinner in central macula and entire quadrants in TDT patients compared to healthy individuals; however, all RNFL measurement thicknesses were comparable between the two groups. Close monitoring of TDT patients by periodic ophthalmologic examinations with more focus on diabetic patients, patients with severe anemia and iron overload should be warranted.

Comparison of post-urethroplasty complication rates in pediatric cases with hypospadias using Vicryl or polydioxanone sutures.

Objective: Hypospadias is a common congenital problem among male newborns. Both rapid absorbable sutures (polyglactin, Vicryl) and delayed absorbable sutures (polydioxanone, PDO) are used in hypospadias repair based on the surgeon's preference. This study was conducted to compare post-urethroplasty complication rates in pediatric patients with hypospadias using Vicryl or PDO sutures. Methods: This is a retrospective study which was designed and performed on 583 children aged 1-7 years old who had undergone hypospadias repair from January 2012 to December 2018. Required data were obtained from the patients' medical records. Results: Overall, post-surgical complications were observed in 60 (10.3%) patients comprising urethro-cutaneous fistula (n=39, 6.7%), meatal stenosis (n=10, 1.7%), urethral stricture (n=7, 1.2%), and glans dehiscence (n=4, 0.7%). The mean age of the children with complications was 3.0±1.3 years. According to Kaplan-Meier estimate, the interval between surgery and development of complications was significantly shorter in the Vicryl group (p=0.037). Overall, complications were more prevalent in Vicryl suture than PDO suture (15.1% vs. 5.3%, p<0.001). Regression model revealed that in comparison to the distal type, proximal hypospadias (odds ratio [OR]:103.9, 95% confidence interval [CI]: 32.2-334.9, p<0.001) and mid-shaft hypospadias (OR: 82.9, 95% CI: 25.9-264.6, p<0.001) while using Vicryl suture instead of PDO suture (OR: 62.4, 95% CI: 21.2-183.8, p<0.001) increased the odds of developing post-urethroplasty complications. Conclusion: We suggest PDO suture in the repair of hypospadias due to its lower complication rate, especially in cases of proximal and mid-shaft hypospadias which can get more complicated than the distal type.

Efficacy and Safety of Sinopharm Vaccine for SARS-CoV-2 and breakthrough infections in Iranian Patients with Hemoglobinopathies: A Preliminary Report.

Background: The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to high morbidity and mortality worldwide. Vaccination against SARS-CoV-2 is a leading strategy to change the course of the COVID-19 pandemic. Aims of the study: Our aim was to investigate the efficacy and side effects of the Sinopharm vaccine in patients with hemoglobinopathies in Iran and the frequency of breakthrough infection after a full course of vaccination. Methods: A multicenter cross-sectional study of 434 patients with hemoglobinopathies (303 ß-thalassemia major, 118 ß-thalassemia intermedia, and 13 sickle-thalassemia) were conducted from March to July 2021 in IRAN. All patients have received the first dose of the China Sinopharm vaccine and received the second dose of the vaccine 28 days apar. Antibody testing: Detection of immunity after vaccination was evaluated by commercial enzyme-linked immunosorbent assay (Pishtazteb ELISA commercial kit), including a surrogate virus neutralization test (sVNT), for detection of SARS-CoV-2 immunoglobulins (IgA, IgM, IgG), total neutralizing antibody (NAb). Results: The mean age of patients was 35.0 ± 8.5 (from 18 to 70) years, and 55.6% were positive for the antibody. Overall, 48.2% of the studied population had at least one side effect after vaccination. The most frequent side effects were fever and chills, dizziness, and body pain. A total of 90 (20.7%) vaccinated patients developed breakthrough infections after two doses of Sinopharm vaccination. Disease severity was recorded, and it was classified as mild in 77.8%, moderate in 13.6%, and severe in 7.4% of patients. One 28-year-old woman with ß-thalassemia major died eight days after diagnosing a breakthrough SARS-CoV-2 infection. Conclusion: No safety concerns were identified in patients who received two doses of the Sinopharm vaccine. Its efficacy was not optimal due to the lack of effect on new variations of the virus. However, our data show that it seems to be protective against the severity of COVID-19 infection in patients with hemoglobinopathies. The frequency of breakthrough infections after two doses of Sinopharm vaccination supports the evolving dynamic of SARS-CoV-2 variants requiring special challenge since such infection may represent a risk for vulnerable patients.

Atopy manifestations in pediatric patients with acute lymphoblastic leukemia: correlation assessment with interleukin-4 (IL-4) and IgE level.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common type of cancer in the age range of under 15 years old and accounts for 25-30% of all childhood cancers. Although conventional chemotherapy regimens are used to improve the overall survival rate, it has been associated with some complications, amongst which allergic manifestations with unknown mechanisms are more common. METHODS: Our study compared serum IgE and IL-4 concentration, as a hallmark of allergic responses in pediatric ALL patients before and after 6 months of intensive (high-dose) chemotherapy, to show whether changes in the level of these markers may be associated with atopy. Serum level of IL-4 and IgE was measured using enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The results showed that the level of IgE and IL-4 increased following chemotherapy in both ALL patients with and without atopy. In addition, post-chemotherapy treatment IgE and IL-4 levels were significantly elevated in patients with atopy compared to those without it. The difference between baseline and post-chemotherapy level of IgE and IL-4 was significantly higher in patients with atopy compared to those without it. CONCLUSIONS: To the best of our knowledge, this is the first study that showed a connection between post-chemotherapy allergic manifestations in pediatric ALL patients and IL-4 and IgE level. Flow cytometry analysis of the T-helper 2 (Th2) lymphocytes and other allergy-related T cell subsets like Tc2 and Th9 as well as the study of the genetic variations in atopy-related genes like IL-4/IL-4R, IL-5, IL-9, IL-13, and high affinity FcεRI IgE receptor and also HLA genes is necessary to clearly define the underlying mechanism responsible for post-chemotherapy hypersensitivity reaction in pediatric ALL patients.

Oncogenic and tumor suppressor genes expression in myeloproliferative neoplasms: The hidden side of a complex pathology.

BACKGROUND: The present study aimed to explore the changes in the expressions of six tumor-related genes in myeloproliferative neoplasms (MPNs). The study population included 130 patients with MPNs (52 with chronic myeloid leukemia (CML), 49 with essential thrombocythemia (ET), 20 with polycythemia vera (PV), and 9 with primary myelofibrosis (PMF)) and 51 healthy individuals. METHODS: The expression profiling of six genes (ADAMTS18, CMTM5, CDKN2B, DCC, FHIT, and WNT5B) in the peripheral blood granulocyte cells was explored by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: The patients with MPNs showed significant downregulation of CMTM5 (EFC = 0.66) and DCC (EFC = 0.65) genes in contrast to a non-significant upregulation of ADAMTS18, CDKN2B, FHIT, and WNT5B genes. Downregulation of DCC was consistent in all subtypes of MPN (EFC range: 0.591-0.860). However, CMTM5 had a 1.22-fold upregulation in PMF in contrast to downregulation in other MPN subtypes (EFC range: 0.599-0.775). The results revealed a significant downregulation in CMTM5 and DCC at below 60-years of age. Furthermore, female patients showed a clear-cut downregulation in both CMTM5 and DCC (EFC DCC: 0.436 and CMTM5: 0.570), while male patients presented a less prominent downregulation with a borderline p-value only in DCC (EFC: 0.69; p = 0.05). CONCLUSIONS: Chronic myeloid leukemia cases showed a significant upregulation of WNT5B, as a known oncogenesis gene. Two tumor suppressor genes, namely DCC and CMTM5, were downregulated in the patients with MPNs, especially in females and patients below 60 years of age.

Comparative Effectiveness of Peg-Asparaginase and L-Asparaginase on Coagulation Markers Among Pediatric Patients with Acute Lymphoblastic Leukemia.

BACKGROUND: Asparaginase (ASP), a chemotherapy component in the acute lymphoblastic leukemia (ALL) treatment, could impair normal coagulation state. Usually, a decline in the levels of several coagulation factors occurs which ultimately could lead to thrombotic events and abnormal coagulation tests. In this study, we aimed to compare the effects of two different subtypes of ASP, pegylated asparaginase (PEG-ASP) and L-asparaginase (L-ASP) on coagulation markers and test among 40 pediatric patients with ALL. METHODS: In this cohort study a total of 40 pediatric patients with newly diagnosed ALL were enrolled and divided into two groups by simple randomization. In group A, 20 patients received PEG-ASP while in group B, 20 patients received L-ASP during the induction treatment. Coagulation markers included prothrombin time (PT), partial thrombin time (PTT), protein-C (Pr-C), protein-S (Pr-S), and antithrombin III (ATIII) and were assessed before start and after of induction chemotherapy. RESULTS: Coagulation profile including PT, PTT, INR, Pr-C, Pr-S, and ATIII before start of treatment were not statistically significant between the two groups. Anticoagulant factors decreased significantly after consuming both drugs. Tests for PT and INR of those who took L-ASP decreased significantly. Overall, when comparing the changes of the six studied factors, ATIII and Pr-C were the significant factors which were different between groups. CONCLUSIONS: ASP has a negative effect on anticoagulant factors including (ATIII, Pr-C, Pr-S). Additionally, the negative effect of L-ASP on anticoagulant factors was more prominent than PEG-ASP. Therefore, the risk of thrombosis probably was negligible in PEG-ASP in comparison with L-ASP.