Palliative care journal publications by country as a metric for palliative care development level.

OBJECTIVE: There is a growing interest in developing a scientific research metric to assess the level of palliative care (PC) development in countries. This study assesses a metric based on publishing in specialised PC journals as an indicator for the level of PC development. METHODS: A 3-year average articles per million population per year (3y-AAMY) metric was calculated using documents published in 19 specialised PC journals indexed in Scopus database. Countries were categorised into six levels starting with level '0' with no publications then levels Q1 to Q5 according to the 3y-AAMY quintiles (Q5=best performance). The relationship between the 3y-AAMY and the level of PC development in countries and opioid consumption figures was tested. RESULTS: During 2016-2018, 6610 eligible documents were published in the selected 19 journals. The median (IQR) 3y-AAMY of 191 countries was 0.0123 (0-0.237). The 3y-AAMY differed significantly among the levels of PC development, being 0 (IQR:0-0) for category 1 (no known activity) countries and 1.129 (IQR:0.286-4.625) for category 4B (advanced integration) countries (Kruskal-Wallis test p<0.000001 and Jonckheere-Terpstra trend test p<0.00001). The correlation between the 3y-AAMY and average opioid consumption was a highly significant positive one (Spearman's ρ=0.681, p<0.0001). Furthermore, opioid consumption differed significantly between the 3y-AAMY categories being highest for Q5 countries (Kruskal-Wallis test p<0.000001 and Jonckheere-Terpstra trend test p<0.00001). CONCLUSION: A metric based on publishing in specialised PC journals correlates significantly with the levels of PC development and opioid consumption in countries and may be used alongside other indicators for the assessment of PC development.

Contribution of Eastern Mediterranean Region countries to palliative care journals from 1991 to 2020 and its relationship to the development of palliative care.

BACKGROUND: Palliative care (PC) is in an early stage of development in the Eastern Mediterranean Region (EMR) of the World Health Organization. A metric based on publishing in specialized PC journals may be useful in assessing PC development. This study was conducted to describe the contribution of EMR countries to PC research and to study the relationship between this contribution and the levels of PC development. METHODS: The Scopus database was used to search 21 PC journals (1991-2020) for articles with at least one EMR-affiliated author independently of his/her position in the article. As an indicator, the 3-year average articles per million population per year (AAMY) was calculated. Changes over time were calculated through a regression analysis. The relationship between the AAMY and the level of PC development and opioid consumption were assessed through Mann-Witney test using the worldmap PC development categories as a proxy, and Spearman analysis, respectively. RESULTS: The number of articles published during the 30-year period was 31,108 of which 402 (1.3%) were EMR-affiliated. There was a steady rise in the AAMY of the EMR (R2 = 0.894). The number of EMR-affiliated articles increased from 3 in the period 1991-1995 to 191 in 2016-2020. The 2018-2020 AAMY was significantly higher in countries with greater PC development than in those without (median [IQR] = 0.0975 [0.0254-0.1802] and 0.0098 [0-0.0256], p = 0.042). Also, it was significantly higher in countries that progressed to a higher level of PC development between 2006 and 2017 (p = 0.0159). There was a significant positive correlation between the average opioid consumption for the years 2017-2019 and the AAMY for the same period (p = 0.0043). CONCLUSIONS: There is a slow steady progress in the contribution of EMR countries to PC journals, which corresponds to the level of PC development and its progress in the region. A metric based on the contribution to specialized PC journals may be a useful indicator of PC development.

The Influence of Interleukin-2 Gene Polymorphisms on the Risk and Clinical Outcome of Non-Hodgkin Lymphoma.

Polymorphisms in the IL-2 gene are associated with various diseases and cancers including non-Hodgkin lymphoma (NHL). The aim of the study is to assess the impact of IL-2 genetic polymorphisms [- 330 T/G (rs2069762) and + 114 T/G (rs2069763)] on the susceptibility and prognosis of NHL. Sixty patients with NHL as well as 60 age and sex matched healthy control subjects are included in this study. IL-2 genotypes were determined by Polymerase Chain Reaction-Restriction Fragment length Polymorphism assay (PCR-RFLP). Our study revealed that both IL-2 rs2069762 and rs2069763 gene polymorphisms are associated with increased risk of developing NHL; OR = 3.609 (95% CI = 1.527-8.417) and 4.142 (95% CI = 1.637-10.538) respectively. Moreover, the simultaneous presence of both polymorphisms is associated with about 6 fold increased risk of developing NHL. Also, IL-2 rs2069762 and rs2069763 gene polymorphisms increase the risk of unfavorable prognosis with OR = 17.300 (95% CI = 3.392-87.725) and 10.424(95% CI = 1.870-58.413) respectively. These findings suggest that IL-2 (rs2069762) and (rs2069763) gene polymorphisms could be involved in the development of NHL.

The Development of FVIII Inhibitors in Relation to IL10 Gene Polymorphism in Hemophilia A Egyptian Pediatric Patients.

BACKGROUND: Development of inhibitors against Factor VIII (FVIII) in hemophilia A patients is a serious complication of therapy. Many cytokines, including interleukin-10 (IL10), may affect inhibitor development; however, literature data are not sufficient to prove this association. The aim of this study was to investigate the relation between FVIII inhibitor formation and IL10-1082A/G polymorphism among Egyptian hemophiliacs. METHODS: Patients were screened for FVIII inhibitors using the Bethesda method. IL10-1082A/G polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Six patients (12%) developed inhibitors. No statistically significant difference was found between inhibitor positive and negative patients regarding IL10-1082A/G genotypes, disease severity, or treatment-related variables (type of FVIII received, treatment regimen, age at first exposure to FVIII, and frequency of replacement therapy). CONCLUSIONS: FVIII inhibitor formation in this group of Egyptian hemophiliacs was not correlated to IL10-1082A/G polymorphism, disease severity, or any of the treatment variables.

Prevalence of Hepatitis C among Egyptian Children with Sickle Cell Disease and the Role of IL28b Gene Polymorphisms in Spontaneous Viral Clearance.

BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) is a major health problem in Egypt with its prevalence estimated to be 14.7% among the general population in 2008. Patients receiving frequent blood transfusions like those with sickle cell disease (SCD) are more exposed to the risk of acquiring HCV. IL28B gene polymorphisms have been associated with spontaneous HCV clearance. This study aims to determine the prevalence of HCV infection among children with SCD and to investigate the relation between IL28B gene polymorphisms and spontaneous HCV clearance. METHODS: Seventy SCD patients were screened for HCV antibody. HCV-positive patients were tested for the level of HCV RNA using quantitative real-time PCR. IL28B polymorphisms (rs 12979860 SNP and rs 12980275 SNP) were detected using TaqMan QRT-PCR and sequence-specific primers PCR respectively. RESULTS: Sixteen patients (23%) were HCV antibody positive, 9 of them (56.3%) had undetectable HCV RNA in serum, and 7 (43.7%) had persistent viremia. Genotypes CC/CT/TT of rs12979860 were found in 30 (42.9%), 29 (41.4%) and 11 (15.7%) patients and rs12980275 AA/AG/GG were found in 8 (11.4%), 59 (84.3%) and 3 (4.3%) patients. There was no significant difference in the frequency of IL28B (rs 12979860 and rs12980275) genotypes among HCV patients who cleared the virus and those with persistent viremia (p=0.308 and 0.724 respectively). CONCLUSION: Egyptian SCD patients have a high prevalence of HCV. Multi-transfused patients still exposed to the risk of transmission of HCV. IL28B gene polymorphismsare not associated with spontaneous clearance of HCV in this cohort of Egyptian children with SCD.

Hepatitis C among Egyptian Patients Referred for Bone Marrow Examination: Seroprevalence and Analysis of Hematological Findings.

Hepatitis C is a significant public health problem in Egypt where the highest prevalence (14.7%) of hepatitis C virus (HCV) exists. HCV prevalence is even higher among clinical populations and groups at risk of exposure to infection. Chronic HCV infection is associated with several hematological complications that may necessitate bone marrow (BM) examination. The aim of this study is to estimate HCV prevalence among patients referred for BM examination and to explore hematological and BM findings among HCV positive patients. One hundred adult patients referred for BM examination were included in the study and screened for HCV antibodies. Patients' clinical, hematological, and BM findings were recorded. The seroprevalence of HCV among patients referred for BM examination was 42%. The most common indication for BM examination among HCV positive patients was peripheral cytopenias (88.1%). The most common cytopenia detected was thrombocytopenia (85.7%). The most common diagnosis among HCV positive patients was hypersplenism (52.4%) followed by B-lymphoproliferative disorders (19%) and then immune thrombocytopenic purpura (11.9%). In conclusion, HCV prevalence among patients referred for BM examination is higher than that estimated in the general population. Patients with unexplained peripheral cytopenias should be tested for HCV.

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, and GSTP1) in Egyptian pediatric patients with sickle cell disease.

Sickle cell disease (SCD) complications are associated with oxidative stress. Glutathione S-transferases (GSTs) are a group of enzymes that protect against oxidative stress. The aims of this study was to evaluate the prevalence of GSTM1, GSTT1, and GSTP1 gene polymorphisms among homozygous sickle cell anemia patients and to investigate the possible association between the presence of these polymorphisms and SCD severity and complications. Genotyping the polymorphisms in GSTT1 and GSTM1 genes was performed using the multiplex polymerase chain reaction (PCR) method. The GSTP1 ILe105Val polymorphism was determined using PCR-restriction fragment length polymorphism. GSTM1 null genotype was significantly associated with increased risk of severe vaso-occlusive crises (VOC) (odds ratio  =  1.52, 95% confidence interval  =  0.42-5.56, P  =  0.005). We found no significant association between GST genotypes and frequency of sickle cell-related pain, transfusion frequency, disease severity, or hydroxyurea treatment. GSTM1 gene polymorphism may be associated with risk of severe VOC among Egyptian SCD patients.

Detection of trisomy 4 and 10 in Egyptian pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: Improvement in cure rates for children with acute lymphoblastic leukemia (ALL) has focused attention on better methods of identifying patients with increased or decreased risk of treatment failure. Chromosome aberrations have a major role in pediatric ALL risk assessment. The aim of this work is to detect the frequency of trisomy 4 and 10 in Egyptian pediatric ALL patients and to analyze their possible prognostic significance. METHODS: Forty newly diagnosed pediatric ALL patients were subjected to bone marrow aspirate morphological examination and immunophenotyping. Detection of copy number of chromosome 4 and 10 was done using Fluorescence In Situ Hybridization (FISH) technique using whole chromosome painting probes. RESULTS: Combined trisomy 4 and 10 was detected in 7 cases (17.5%), all of them were of B-ALL type. Single trisomy 4 or 10 was not detected in any case. Trisomy positive patients had a statistically significant lower total leucocytic count (p = 0.041), higher platelet count (p = 0.018), and lower blast percentage in peripheral blood (p = 0.016) at diagnosis. CONCLUSIONS: Combined trisomy 4 and 10 identifies a group of ALL patients that have good prognostic indicators. Screening of Egyptian pediatric ALL patients for trisomy 4 and 10 may help in "patients' stratification" aiming to develop a risk-adapted therapy in order to minimize therapy related morbidities particularly in children.

Frequency of CYP2C9 and VKORC1 gene polymorphisms and their influence on warfarin dose in Egyptian pediatric patients.

INTRODUCTION: Warfarin is a widely used anticoagulant that shows a high inter-individual variability in the dose needed to achieve target anticoagulation. In adults, common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex (VKORC1) enzymes, in addition to non-genetic factors, explain this dose variability. In children, data about warfarin pharmacogenetics are limited and inconsistent. METHODS: CYP2C9 (*2 and *3) alleles and the VKORC1 (C1173T and G-1639A) polymorphisms were studied by multiplex real time polymerase chain reaction in 41 pediatric patients who received stable warfarin maintenance dose. RESULTS: The allele frequency of the studied genes was CYP2C9*2 (0.085), CYP2C9*3 (0.12), VKORC1 1173T (0.52), and VKORC1 -1639A (0.54). In univariate analysis, patients' age, weight, and height were significantly (p < 0.0001) associated with warfarin maintenance dose. However, CYP2C9 and VKORC1 gene polymorphisms did not affect warfarin dose. In multivariate analysis, age was found to be the only significant determinant of daily warfarin maintenance dose (p = 0.045). CONCLUSION: Age was the most significant determinant of warfarin dosage in this preliminary study including Egyptian pediatric patients. Further studies involving larger numbers of children are warranted to determine the true impact of genetic factors on warfarin doses in pediatric patients.

Plasma annexin A5, anti-annexin A5 antibodies and annexin A5 polymorphism in Egyptian female patients with systemic lupus erythematosus and antiphospholipid syndrome.

BACKGROUND: Annexin A5 exhibits anticoagulant properties that appear to be defective in patients with antiphospholipid syndrome (APS) resulting in repeated thrombosis and recurrent pregnancy loss (RPL). APS occurs frequently in association with systemic lupus erythematosus (SLE). The present study aimed to find out a possible relationship between annexin A5 (gene polymorphism, antibodies or plasma level) and the pathophysiology of SLE, APS and RPL. METHODS: 47 female patients divided into 3 groups (SLE, APS and RPL) and 20 healthy controls are included in the study. Detection of annexin A5 (-1C/T) gene polymorphism was done by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. Anti-annexin A5 antibodies (IgG and IgM) and annexin A5 plasma level were measured by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: The frequency of annexin A5 (-1C/T) polymorphism was significantly higher in SLE related groups (p = 0.02), but it did not correlate with RPL (p = 0.57) or annexin A5 level (p = 0.5). Anti-annexin A5 IgM level was significantly higher among APS patients and was associated with RPL (p = 0.005, odds ratio = 23.75, 95% confidence interval = 2.15 - 262.48). CONCLUSIONS: Annexin A5 (-1C/T) gene mutation may play a role in the pathophysiology of SLE. Anti-annexin A5 IgM was the antibody associated with RPL in this group of APS patients. Annexin A5 plasma levels are not affected by the presence of annexin A5 (-1C/T) polymorphism.

Mesenchymal stem cells from pediatric patients with aplastic anemia: isolation, characterization, adipogenic, and osteogenic differentiation.

Aplastic anemia is a syndrome of bone marrow (BM) failure characterized by peripheral pancytopenia and marrow hypoplasia. Its exact pathophysiology is still not clear. Mesenchymal stem cells (MSCs) play an important role in providing the specialized BM microenvironment for hematopoietic stem cells survival and differentiation. MSCs were isolated from BM of five patients with aplastic anemia and five controls. MSCs were characterized by morphology and immunophenotyping. Their viability, proliferative capacity, and adipogenic as well as osteogenic differentiation potentials were assessed. MSCs from aplastic anemia patients and controls shared similar spindle-shaped morphology and surface marker expression. MSCs derived from patients with aplastic anemia showed lower viability (74.2 ± 4.44% vs. 97.0 ± 1.58, p < 0.0001) and slower expansion rate as indicated by smaller population doubling and smaller cumulative population doubling from passages 1 to 4 (0.70 ± 0.22 vs. 2.34 ± 0.84; p = 0.009). Besides, aplastic anemia MSCs had poor capacity to differentiate into adipocytic and osteocytic lineages.

The association between hepatitis C virus infection, genetic polymorphisms of oxidative stress genes and B-cell non-Hodgkin's lymphoma risk in Egypt.

Hepatitis C virus (HCV) has been postulated to be an etiological agent for lymphoid malignancies. Polymorphisms in oxidative stress genes as; superoxide dismutase (SOD2), glutathione peroxidase (GPX1), catalase (CAT), myeloperoxidase (MPO) and nitric oxide synthase (NOS2) may influence non-Hodgkin's lymphoma (NHL) risk. HCV screening and polymorphisms in these five genes coding for antioxidant enzymes were studied in 100 Egyptian patients with B cell-NHL and 100 controls to clarify the association between HCV infection, oxidative stress genes polymorphisms and B cell-NHL risk. A significantly higher prevalence of HCV infection was detected among NHL patients relative to controls and this carried a 14-fold increased NHL risk (odds ratio (OR)=14.3, 95% confidence interval (CI)=5.4-38.3, p<0.0001). GPX1 and MPO genetic polymorphisms conveyed increase in B-NHL risk (OR=3.3, 95% CI=1.4-7.4, p=0.004 and OR=4.4, 95% CI=1.3-14.2, p=0.009 respectively). Further analyses stratified by HCV infection revealed that concomitant HCV infection and GPX1 gene polymorphism had a synergetic effect on NHL risk with an OR of 15 (95%CI=2.2-69.6, p<0.0001). In addition, combined HCV infection and MPO gene polymorphisms had a pronounced NHL risk (OR=9.2, 95%CI=2.5-33.9, p<0.0001). SOD2, CAT and NOS2 genetic polymorphisms were not found to confer increased NHL risk. This study revealed that HCV infection is a risk factor for NHL in Egypt. Polymorphisms in GPX1 and MPO genes may influence NHL risk in HCV infected Egyptian patients. Larger scale studies are warranted to establish this genetic susceptibility for NHL.

The effect of freezing on the recovery and expansion of umbilical cord blood hematopoietic stem cells.

OBJECTIVES: Cell populations residing in waste tissues (cord blood, umbilical cord, and placenta) may be collected without any medical or ethical contraindications concerning the mother or newborn baby. Cord blood hematopoietic stem cells are routinely used for clinical transplants; however, the low cell dose of the graft limits their therapeutic efficacy as it is associated with increased delayed or failed engraftment. The cell dose can be increased, and the efficacy of cord blood transplant potentially improved, by ex vivo expansion before transplant. MATERIALS AND METHODS: Twelve umbilical cord blood samples were included. The effect of cord blood storage at -80 degrees C on CD34+ cell count (mean -/+ standard deviation [SD]), cell viability (mean -/+ SD percent), and cell cycle status (percent quiescent versus dividing) was estimated. Ex vivo culture of cord blood mononuclear cells was done before storage, and after 1 week of freezing, and after 2 weeks of freezing. Ex vivo liquid culture was performed with media supplemented with stem cell factor, interleukin-3 (IL-3), and both. RESULTS: The count of CD34+ cells in pre-expansion aliquots decreased from 15.00 +/- 9.96 x 106 cells before freezing to 7.70 -/+ 3.20 x 106 cells after 2 weeks of freezing (P = .024). Cell viability in pre-expansion aliquots decreased from 99.5% -/+ 1.0% before freezing, to 52.5% -/+ 27.5% after 1 week of freezing (P = .013) and to 32.5% -/+ 9.5% after 2 weeks of freezing (P = .001). Mean fold of cell expansion and proportion of quiescent versus dividing cells did not change significantly from before to after freezing, and was not significantly different for culture with stem cell factor, IL-3, or both. CONCLUSION: Although freezing decreased cell count and viability, it did not impair the expansion potential of cord blood hematopoietic cells. Whether IL-3 or stem cell factor should be considered as essential components of expansion media is uncertain.

Clinical significance of serum anti-annexin V antibodies in Egyptian patients with scleroderma.

The pathogenesis of scleroderma encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations. We investigated the prevalence of anti-annexin V IgG and IgM antibodies in sera of scleroderma patients and their relation to the presence of other antibodies and development of disease morbidity. Sera of 40 scleroderma patients and 15 healthy controls were examined for IgG and IgM anti-annexin V antibodies by ELISA and anticentromere antibodies by indirect immunofluorescence. Serum level of anti-annexin V IgG antibodies in scleroderma patients was significantly higher than that of the control (P < 0.001) and correlated significantly with the presence of digital ischemia (P = 0.023) and pulmonary fibrosis (P = 0.02). IgM isotype was comparable between patients and controls (P = 0.317). Anticentromere antibodies are more prevalent in the limited cutaneous subtype (P = 0.017). In conclusion, measurement of serum anti-annexin V IgG antibodies in scleroderma patients may be important for early diagnosis of vascular and pulmonary complications.