The association of bacterial biofilm and middle ear mucosa in patients with mucosal chronic suppurative otitis media.

OBJECTIVES: To evaluate the bacterial biofilm's role in mucosal chronic suppurative otitis media (CSOM) utilizing scanning electron microscopy (SEM). METHODS: This study involved 123 participating patients with active and inactive mucosal CSOM who are undergoing tympanomastoid surgery. SEM was used to examine middle ear mucosa biopsies for the development of biofilms. Middle ear discharge or mucosal swabs from patients were cultured to detect any bacterial growth. The biofilm formation was correlated to the culture results. RESULTS: The biofilm was present in 69.9 % of patients (59% of them were with active mucosal CSOM) and absent in 30.1% of the patients (70% of them were with inactive mucosal CSOM), being more statistically significant in active mucosal CSOM (p-value = 0.003). A correlation that was statistically significant was found between active mucosal CSOM and higher grades (3 and 4) of biofilms (p-value <0.05). The mucosal CSOM type and the results of the culture had a relationship that was statistically significant (p-value <0.001). 60% of patients had positive culture (70% of them were with active mucosal CSOM). There was a statistically significant relation between Pseudomonas aeruginosa bacterial growth and active mucosal CSOM (p-value = 0.004) as well as higher grades of biofilms in mucosal CSOM. CONCLUSION: Mucosal CSOM, especially the active type, is a biofilm-related disease. There is a significant relation between the state of mucosal CSOM (active or inactive) and culture results with predominance of Pseudomonas aeruginosa bacterial growth in active mucosal CSOM and in higher grades of biofilms in mucosal CSOM.

Ascitic Fluid Calprotectin And Ratio Of Calprotectin To Total Protein In Spontaneous Bacterial Peritonitis.

Objectives: To evaluate the diagnostic and prognostic role of ascitic fluid calprotectin and its ratio to total protein in spontaneous bacterial peritonitis cases. Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2019 to December 2020, and comprised cirrhotic patients of either gender with ascites. Diagnostic abdominal paracentesis was performed for all patients and ascetic fluid calprotectin was measured. Patients were followed for development of spontaneous bacterial peritonitis or mortality. Data was analysed using SPSS 20. RESULTS: Of the 90 patients, 61(67.7%) were males and 29(32.2%) were females. There were 67(74.4%) patients with spontaneous bacterial peritonitis; 48(71.6%) males and 19(28.3%) females with mean age 60.42±8.3 years. The remaining 23(25.5%) did not have spontaneous bacterial peritonitis; 13(56.5%) males and 10(43.4%) females with mean age 59.7±7.4 years. The patients had significantly higher calprotectin, and calprotectin/total protein ratio (p<0.05). Logistic regression identified ascitic fluid calprotectin as a significant predictor of mortality (p=0.05). The non-survivors had significantly higher ascitic fluid calprotectin and calprotectin/total protein ratio compared to the survivors (p<0.05). CONCLUSIONS: Ascites calprotectin level and itsratio to total protein wasfound to be accurate diagnostic and predictive biomarkers for spontaneous bacterial peritonitis.

Gremlin-1 Level In Polycystic Ovary Syndrome And Its Clinical Correlations; A Case Control Study.

Objectives: To evaluate the involvement of the level of Gremlin-1 in serum and follicular fluid in the diagnosis of polycystic ovary syndrome. Method: The case-controlstudy was conducted at the Kafrelsheikh University Hospital, Egypt, from September 2021 to February 2022, and comprised women with polycystic ovary syndrome and healthy controls. All participants were subjected to a detailed clinical assessment, complete clinical examination and hormonal profile assessment. Gremlin1 concentrationsin plasma and follicular fluid samples were assessed by a double-antibody sandwich enzyme-linked immunosorbent assay kit. Data was analysed using SPSS 20. RESULTS: Of the 90 subjects, 45(50%) were patients with a mean age of 29.53±4.82 years, and 45(50%) were controls with a mean age of 30.89±6.08 (p>0.05). Mean weight, body massindex, waist circumference and waist-hip ratio were significantly higher in patients compared to controls (p<0.05). Serum and follicular fluid Gremlin-1 levels were significantly higher in the patient group (p<0.05). The best cutoff of serum Gremlin-1 in the diagnosis of polycystic ovary syndrome was ≥1.325ng/ml with area under curve 0.857,sensitivity 93.3%,specificity 68.9%, positive predictive value 75%, negative predictive value 91.2% and overall accuracy 81.1%. The best cutoff of follicular fluid Gremlin-1 in the diagnosis of polycystic ovary syndrome was ≥1.725ng/ml with area under curve 0.789,sensitivity 73.3%,specificity 68.9%, positive predictive value 70.2%, negative predictive value 72.1% and overall accuracy 71.1%. CONCLUSIONS: There was a strong correlation between serum and follicular Gremlin-1 levelsin polycystic ovary syndrome patients.

Assessment Of Endometrial Integrin Beta 5 In Women With Unexplained Recurrent Pregnancy Loss.

Objectives: To examine the relationship between endometrial integrin beta 5 level and risk of recurrent pregnancy loss. Method: The descriptive, prospective, observational, case-controlstudy was conducted at the Kafrelsheikh University Hospital, Egypt, from January to May 2022, and comprised women aged up to 35 years with at least 1 live birth delivery beyond 20-week gestation with normal thyroid and prolactin levels. Age-matched normal fertile women were enrolled as controls. All the participants were subjected to detailed history and complete clinical examination. Endometrial integrin beta 5 was assessed using an antibody sandwich enzyme-linked immunosorbent assay. Data was analysed using SPSS 20. RESULTS: Of the 50 subjects, 25(50%) were cases with a mean age of 26.72±2.64 years, and 25(50%) were controls with a mean age of 25.36±2.16 years. The integrin beta 5 level was significantly lower among the cases than the controls (p<0.05). The best cut-off level of serum integrin beta 5 was ≤2.5765 with area under curve 0.886, sensitivity 88%, specificity 76%, positive predictive value 78.6%, negative predictive value 86.4%, and accuracy 82%. CONCLUSIONS: Therewas an inverse correlationbetween endometrial integrinbeta 5 andthe risk ofrecurrentpregnancy loss.

Relation Between Interleukin-6, Interleukin-10 And Interleukin-2 Receptor And Mortality In Severely Ill COVID-19 Patients.

Objectives: To investigate the relation involving soluble interleukin-2 receptor, interleukin-6 and interleukin-10 in hospitalised patients with severe coronavirus disease-2019 infection. Method: This single-centre cohort study was conducted at the Kafrelshiekh University Hospital, Egypt, from January to June 2022, and included all patients of either gender who were hospitalised with severe infection with the coronavirus disease-2019 isolation ward. Chemiluminescence immunoassay method was used to measure levels of procalcitonin, ferritin, soluble interleukin-2 receptor, interleukin-6 and interleukin-10. Data was analysed using SPSS version. 25. RESULTS: Of the 250 patients with median age 57.5 years (interquartile range: 45.8-66.0 years), 147(59%) were males and 103(41%) were females. Of them, 102(40.8%) patients died; 68(66.7%) males, 34(33.3%) females, median age 60.0 years (interquartile range: 48.8-70.0). Among the 148(59.2%) survivors, 79(53.4%) were males and 69(46.6%) were females, while the overall median age was 55.0 years (interquartile range: 41.5-65.8 years). The survivors had significantly lower levels of soluble interleukin-2 receptor, interleukin-6 and interleukin-10 (p<0.001). Correlation analysisidentified significant positive correlation between IL-2R, IL-6 and IL-10 levels and almost all the inflammatory and coagulation parameters, including C-reactive protein, lactate dehydrogenase, procalcitonin, ferritin, D-dimer and fibrinogen (p<0.05). CONCLUSIONS: Elevated levels of soluble interleukin-2 receptor, interleukin-6 and interleukin-10 were found to be associated with greater risk of mortality in coronavirus disease-2019 patients.

Assessment Of Serum Vitamin D Level In Children With Type 1 Diabetes Mellitus: A Cross-Sectional Study.

Objectives: To estimate vitamin D levelsin children with type 1 diabetes, and to evaluate itsrole in the pathogenesis and progress of the disease. Method: The cross-sectional study was conducted at the Paediatric Department of Kafrelsheikh University Hospital, Egypt, from November 2019 to August 2021, and comprised children of either gender aged 3-18 years who were either inpatients or visiting the paediatric outpatient clinic. The subjects were enrolled into 3 groups. Those with newly diagnosed type 1 diabetes were in group A, those with established type 1 diabetes were in group B, and healthy children matched for age and gender and randomly selected were in the control group C. Glycated haemoglobin, serum fasting C-peptide, and serum vitamin D levels were evaluated using quantitative colorimetric determination, an automated analyser, and enzyme-linked immunosorbent assay, respectively. Data was analysed using SPSS 25. RESULTS: Of the 80 subjects, 30(37.5%) were in group A; 17(56.7%) boys and 13(43.3%) girls with mean age 7.77±2.95 years. In group B, there were 30(37.5%) subjects; 14(46.7%) boys and 16(53.3%) girls with mean age 9.6±3.62 years. There were 20(25%) subjects in group C; 10(50%) boys and as many girls with mean age 8.38±2.68 years (p>0.05). Glycated haemoglobin,serum fasting C-peptide and serum vitamin D wassignificantly different between the control group and the treatment groups (p<0.05). Between the treatment groups, group B had better markers than group A (p<0.05). CONCLUSIONS: Serum vitamin D deficiency may play a role in the pathogenesis and insulin sensitivity in cases of type 1 diabetes.

High-resolution Melting Analysis for NOTCH1 c.7541-7542delCT Mutation in Chronic Lymphocytic Leukemia: Prognostic Significance in Egyptian Patients.

The present study aimed to detect the prevalence of NOTCH1 c.7541-7542delCT mutation in Egyptian CLL patients using HRM assay and to assess its relation to patients' survival. The study included 50 newly diagnosed treatment-naïve CLL patients and 50 age and sex matched healthy controls. NOTCH1 c.7541-7542delCT mutation was detected using High-resolution melting (HRM) assay and direct Sanger sequencing. Outcome parameters included progression free survival (PFS) and overall survival (OS). NOTCH1 c.7541-7542delCT mutation was detected in 5 (10.0%) of CLL patients. No controls had NOTCH1 c.7541-7542delCT mutation. Similar results were obtained by direct Sanger sequencing yielding a sensitivity and specificity of 100.0% for HRM in detection of NOTCH1 c.7541-7542delCT mutation in the studied patients. In univariate analysis, predictors of OS included Trisomy 12, high LDH, presence of NOTCH1 c.7541-7542delCT mutation and lack of CR. In multivariate analysis, only lack of CR was found as a significant predictor of OS. HRM analysis is a sensitive method for detection of NOTCH1 c.7541-7542delCT mutation in CLL patients. This mutation may be linked to poor disease prognosis.

Prognostic significance of complement factors in severely ill patients with COVID-19.

Coagulopathy, cytokine release, platelet hyperactivity and endothelial activation are regarded as potential major contributors to COVID-19 morbidity. Complement activation might provide a bridge linking these factors in severe COVID-19 illness. In this study, we investigated the prognostic significance of selected complement factors in hospitalized patients with severe COVID-19 infection. The study included 300 hospitalized adults with severe COVID-19 infection. Complement factors (C3, C3a, C4, sC5b-9) were assessed by commercial ELISA kits. Outcome parameters included mortality, intensive care unit admission and duration of hospital stay. It was found that survivors had significantly higher serum C3 (median (IQR): 128.5 (116.3-141.0) mg/dL vs 98.0 (70.0-112.8) mg/dL, p<0.001) and C4 (median (IQR): 36.0 (30.0-42.0) mg/dL vs 31.0 (26.0-35.0) mg/dL, p<0.001) levels when compared with non-survivors. On the other hand, it was shown that survivors had significantly lower C3a (median (IQR): 203.0 (170.3-244.0) ng/mL vs 385.0 (293.0-424.8) ng/mL, p<0.001) and sC5b-9 (median (IQR): 294.0 (242.0-318.8) ng/mL vs 393.0 (342.0-436.5) ng/mL, p<0.001) levels when compared with non-survivors. Multivariate logistic regression analysis identified C3a (OR: 0.97 (95% CI 0.96 to 0.99), p<0.001) and C4 (OR: 0.92 (95% CI 0.86 to 0.98), p=0.011) levels as significant predictors of mortality. In conclusion, serum levels of complement factors are related to mortality in severely ill patients with COVID-19.

Fecal calprotectin as a predictor of COVID-19 severity

Coronavirus disease 2019 (COVID-19) is highly transmittable through contact with respiratory droplets. The virus is also shed in fecal matter. Some patients may present with effects in more than one system; however, there are no defined biomarkers that can accurately predict the course or progression of the disease. The present study aimed to estimate the severity of the disease, to correlate the severity of the disease with biochemical predictors, to identify valuable biomarkers indicative of gastrointestinal disease, and to determine the cutoff values. A cross-sectional study was conducted on COVID-19 patients admitted to the Kafrelsheikh University Hospital (isolation unit) between July 10, 2020, and October 30, 2020. The diagnosis of COVID- 19 was confirmed via reverse transcription-polymerase chain reaction (RT-PCR), which was employed for the detection of the viral RNA. We conclude that lymphopenia, elevated C-reactive protein (CRP) level, and liver enzymes were among the most important laboratory findings in COVID-19 patients. Statistically significant differences in platelet count, neutrophil count, D-dimer level, and fecal calprotectin levels were observed among patients presenting with chest symptoms only and patients with both chest and gastrointestinal symptoms (p=0.004;<0.001; 0.010; 0.003; and<0.001, respectively). C-reactive protein, D-dimer, and fecal calprotectin levels positively correlated with disease severity. The cutoff value for fecal calprotectin that can predict gastrointestinal involvement in COVID-19 was 165.0, with a sensitivity of 88.1% and a specificity of 76.5%. (AU)

Relation between levels of toll-like receptors 3 and 7 and clinical profile of Child-Pugh B cirrhotic patients.

AIM OF THE STUDY: Growing data show that toll-like receptors (TLRs) have considerable roles in the pathogenesis of many liver diseases. We aimed to study the relation between TLR3 and TLR7 levels and clinical manifestations of liver decompensation among hepatitis C virus (HCV)-infected Child-Pugh B patients. MATERIAL AND METHODS: This study included 60 adult patients with Child-Pugh B liver cirrhosis on top of untreated HCV infection. We performed a two-step clustering algorithm depending on TLR-3 gene expression, TLR-7 gene expression, and other influential patients' characteristics. RESULTS: Patients were optimally divided into 2 clusters, each cluster containing 30 patients. The average silhouette score of the clustering algorithm was 0.52, indicating a good clustering power of the model. Patients in cluster 1 showed lower relative expression of TLR3 (0.188 vs. 0.29). The same was true of TLR7 (0.20 vs. 0.31). All patients within cluster 1 had lower limb edema and 93% of them had ascites. On the other hand, no one within cluster 2 had ascites or lower limb edema. The mean platelet count was lower in patients within cluster 1 (74,000 vs. 100,000 cell/mm3). The mean international normalized ratio (INR) level was higher in cluster 1 (1.61 vs. 1.3). The mean Model for End-Stage Liver Disease (MELD) score was higher in cluster 1 (15 vs. 10). CONCLUSIONS: From these results, we can suggest that lower TLR3 and TLR7 can lead to worse clinical manifestations among patients with HCV-related liver cirrhosis. A deeper exploration of this point can open the door for new approaches for managing decompensated cirrhosis.

Serum Visfatin as a Diagnostic Marker of Active Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) have been reported to be caused by a complex interplay of immunological, infectious, and genetic factors. Previous studies have suggested that adipokines play a role in IBD by inducing proinflammatory cytokines. We aimed to evaluate the role of visfatin in the diagnosis algorithm of active IBD. METHODS: 85 newly diagnosed IBD patients [56 diagnosed with ulcerative colitis (UC) and 29 with Crohn's disease (CD)] and 30 healthy controls were included. IBD phenotypes were described accordingly to Montreal classification. Hemoglobin, total leucocytic count (TLC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, fecal calprotectin and serum visfatin were measured. RESULTS: The serum visfatin level was found to be significantly higher in patients with IBD than those in the control group (p<0.001). It was significantly positively correlated with CRP, ESR, and FC in both IBD groups. Receiver operating characteristic curve analysis of visfatin in diagnosis of UC revealed an area under curve of 0.911. At cutoff ≥1.4 ng/ml, the sensitivity was 92.9% and the specificity was 86.7%.. In CD group, at the same cutoff, AUC was 0.974, sensitivity was 96.6% and specificity was 86.7%. There was a statistically significant elevation of serum visfatin in extensive UC (E3) as compared to the other groups. A cutoff ≥3.25 ng/ml revealed 88.9% sensitivity, and 100% specificity in detection of E3 UC. Serum visfatin was significantly increased in CD stricturing phenotype (B2) as compared to non-stricturing non-penetrating CD (B1). A cutoff ≥3.5 ng/ml revealed 83.3% sensitivity, and 100% specificity in detection of B2. CONCLUSIONS: The serum visfatin level were significantly higher in patients with IBD than in controls. Serum visfatin might be a novel noninvasive marker to detect activity in IBD patients and can be used as predictor of disease extension in patients with UC.

Otitis media with effusion is not a sterile inflammatory process: scanning electron microscope evidence.

PURPOSE: We aimed to demonstrate whether chronic otitis media with effusion (OME) is a sterile condition or biofilms-related disease through direct visualization of middle ear mucosa by Scanning electron microscopy (SEM) and culture of the effusion. METHODS: This case-control study included 60 children in two groups; the case group included 50 patients undergoing ventilation tube insertion (VTI) for Chronic OME (COME), and the control group included ten patients undergoing cochlear implantation (CI) surgery presenting normal middle ear mucosa. Biopsies from both groups' middle ear mucosa were evaluated for biofilm formation using scanning electron microscopy (SEM). Middle ear effusion (MEE) samples from COME patients were cultured on blood agar to detect and identify any bacterial growth. The adenoid size was evaluated and correlated to the biofilm formation in COME patients. RESULTS: There was a significant difference between case and control groups regarding biofilm formation (p-value < 0.001*). Biofilm was evident in 84% of the COME patients (cases group) and absent in the control group. Only 12 COME patients (24%) had positive MEE culture, however, 76.2% of patients with biofilm had a negative culture. Streptococcus pneumonia was the most common otopathogen found either alone or combined with other otopathogens. There was a significant negative correlation between adenoid size and biofilm grade among the studied patients. CONCLUSION: The visual identification of middle ear biofilms indicated their role in chronic OME. Middle ear biofilms need to be expected in children with OME, especially those who do not need adenoid surgery.

Assessment of the effect of platelet rich plasma on the healing of operated sacrococcygeal pilonidal sinus by lay-open technique: a randomized clinical trial.

BACKGROUND: Sacrococcygeal pilonidal sinus disease (PSD) is an infection of the skin and subcutaneous tissue at the upper part of the natal cleft of the buttocks. Excision and healing by granulation "lay-open" method is still more preferable than other methods of midline closure or using flaps but the healing time is lengthy. The present study was performed to assess the healing promotion effect of platelet-rich plasma (PRP) on the pilonidal sinus wounds treated by the lay-open method. METHODS: One hundred patients suffering from PSD were randomly divided into two groups, they were treated by the lay-open method, at General surgery department, Kafr El-Sheik University hospital, Egypt, during the period from December 2018 to December 2019. Group (A) was adopted the regular dressing postoperatively, while group (B) was treated with PRP injection into the wound at 4 and 12 postoperative days. RESULTS: Accelerated rate of wound healing was detected in group (B) in day 10, with a significant difference detected in days 15, 20, 25 and 30 postoperative, with a mean time of complete healing 45 ± 2.6 days in group B, while it was 57 ± 2.4 days in group A with a p-value of 0.001 which indicates considerable effect in the treated group. CONCLUSIONS: PRP injection is an effective new technique in accelerating the healing of pilonidal wound after surgery, with a significant decrease in post-operative pain, complications and an early return to work. TRIAL REGISTRATION: retrospectively registered. TRIAL REGISTRATION NUMBER: 12/35/1016 issued on December 2018 from the Institution Review Board at Kafr El Sheikh University. ClinicalTrials.gov identifier: NCT04430413.

Serum Interleukin-6 Level in Children With Attention-Deficit Hyperactivity Disorder (ADHD).

INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral disorder in children, but its specific etiology and pathophysiology are still incompletely understood. OBJECTIVES: This case-control study aimed to measure the level of serum interleukin-6 (IL-6) as a predictor of the immunologic status in children with ADHD, and to study its correlation with severity of symptoms. SUBJECTS AND METHODS: 60 ADHD children who met the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, criteria for ADHD and 60 control children were subjected to complete history taking, clinical examination, and psychometric tests. Serum interleukin-6 of ADHD patients and control children was measured by enzyme-linked immunosorbent assay. RESULTS: The mean serum level of IL-6 was 22.35 (95% confidence interval [CI], 17.68-26.99) in ADHD patients, and it was 5.44 (95% CI, 4.81-6.06) in controls. A significantly higher level of IL-6 was reported in ADHD patients compared with controls ( P = .001). No significant correlation was found between serum IL-6 level and either the Intelligence Quotient (IQ) or the Conners' Parent Rating Scale score. CONCLUSION: Serum IL-6 values were significantly higher in ADHD patients compared to healthy control children. Increased production of IL-6 may play a role in the pathogenesis of ADHD.

Prognostic Value of Transferrin Receptor-1 (CD71) Expression in Acute Lymphoblastic Leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the commonest childhood cancer. Transferrin receptor 1 (CD71) is a trans-membrane glycoprotein which has important role in iron homeostasis by acting as a gatekeeper regulating iron uptake from transferrin and is an attractive target for anti-cancer agents, particularly those that aim to induce lethal iron deprivation in malignant hematopoietic cells. AIM OF THE WORK: To assess the prognostic value of Transferrin receptor -1 (CD71) in children with newly diagnosed ALL. PATIENTS AND METHODS: This study was carried out on 75 patients with newly diagnosed ALL. Transferrin receptor-1 expression was analyzed on the bone marrow blasts by flow cytometry at time of diagnosis with positive CD71 expression is considered when ≥20% of malignant cells express this marker while negative expression is considered when <20% of malignant cells express this marker. RESULTS: Transferrin receptor-1 positive expression was detected in 45 patients (60%) while negative expression was found in the remaining 30 patients (40%). CD71 expression was significantly higher on T- ALL patients compared with B-ALL patients. Positive CD71 expression at diagnosis was significantly associated with bad clinical and laboratory prognostic factors as lymphadenopathy, higher white blood cell count, higher hemoglobin level, lower platelets count, and higher blast cells in peripheral blood and bone marrow and higher lactate dehydrogenase levels'. There were significant differences in disease free survival (DFS) and overall survival (OS) between positive and negative CD71 expression groups with significantly shorter DFS and OS in positive CD71 expression group compared to negative group. CONCLUSION AND RECOMMENDATIONS: 'Positive Transferrin receptor -1 (CD71) expression in patients with ALL is adverse prognostic factor and should be taken in consideration in designing future therapeutic strategies based on patient- specific risk factors'.

Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis.

Children with end-stage renal disease (ESRD) suffer from dyslipidemia and hyperuricemia that might play a causal role in the progression of cardiovascular disease (CVD). The aim of the study is to assess the effects of Vitamin C supplementation on uric acid, ascorbic acid, and serum lipid levels among children on hemodialysis (HD). This prospective study was conducted in the pediatric nephrology unit at Menoufia University Hospital. The study included a total of 60 children with ESRD on maintenance HD therapy. They were divided into two groups: Group I (supplemented group, n = 30) received intravenous Vitamin C supplementation and Group II (control, n = 30) received placebo (intravenous saline) for three months. The results are shown as a mean ± standard deviation. Statistical evaluation was performed by SPSS software (version 11.5) using paired t-test. After supplementation with Vitamin C, the serum Vitamin C and high-density lipoprotein levels increased significantly with a significant reduction in the levels of serum uric acid, cholesterol, low-density lipoproteins, and triglyceride at the end of the study period. No significant changes were observed in the control group. Vitamin C can serve as a useful urate lowering medicine in HD patients to avoid complications of hyperuricemia. Furthermore, it had favorable effects on the lipid profile. This improvement can be considered as a preventive strategy in the progression of CVD in HD patients. Vitamin C supplementation improves ascorbic acid deficiency in these patients.

Prognostic Impact of Neuropilin-1 Expression in Egyptian Children with B-lineage Acute Lymphoblastic Leukemia.

BACKGROUND: Neuropilins are transmembrane glycoproteins that act as receptors for vascular endothelial growth factors and are involved in the process of tumor angiogenesis. OBJECTIVE: The aim of this work was to study the prognostic value of Neuropilin-1 (NRP-1) expression in Egyptian children with B-lineage acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: This study was conducted on fifty children with newly diagnosed B-lineage ALL, admitted to Oncology Unit, Pediatric Department, Tanta University Hospitals in the period from August 2010 to March 2014. This series included 32 males and 18 females with ages ranging from 3-17 years and a mean value of 9 ± 3.5 years. Twenty healthy children, age and sex matched, were also included in this study as a control group. For all patients, the following examens were done: Bone marrow aspiration, cytochemistry, immunophenotyping and estimation of Neuropilin-1 expression on blast cells by flow cytometry. RESULTS: The present study revealed highly significant differences in Neuropilin-1 expression between B-lineage ALL lymphoblasts and control lymphocytes. A significant higher Neuropilin-1 expression was found in pre-B ALL (74.04%) compared with early pre-B (23.55%). Neuropilin-1 positive expression was associated with significantly higher white blood cells count (Mean = 69.3±18.53 ×10(3)/mm(3) versus 32.5±11.64 ×10(3)/mm(3) and p=0.003), bone marrow blasts percentage (Mean=76.12±21.4 % versus 41.2±19.71% and p= 0.003), serum lactate dehydrogenase levels (Mean=1992.2 ± 58.6 unit/L versus 955.1± 234.7 unit/L and p=0.001) at diagnosis compared with negative Neuropilin-1 expression. The levels of Neuropilin-1 on BM blasts at diagnosis were higher in patients who subsequently relapsed (Mean=53.8 ± 27.1) or later died (Mean=81.51 ± 9.94) during the period of follow-up compared to those who achieved and maintained complete remission (Mean=18.17 ± 10.4) with p value of 0.001. Furthermore, patients with higher Neuropilin-1 expression had significantly shorter overall survival (Median 27.99 months and p= 0.0133) and disease-free survival (Median=10.23 months and p= 0.0002) than patients with low Neuropilin-1 expression (Median disease-free survival was 38.7 months). CONCLUSION: Our findings suggest that Neuropilin-1 is a poor prognosis factor in children with B-lineage ALL and so we recommend the inclusion of Neuropilin-1 as a prognostic marker in children with B-lineage ALL. Its presence at high levels suggests a poor prognosis, and the necessity of intensive therapeutic intervention.

Prognostic value of protease activated receptor-1 in children with acute lymphoblastic leukemia.

BACKGROUND: Acute Lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that proliferate and replace the normal hematopoietic cells of the bone marrow. Protease-activated receptors (PARs) comprise a family of trans-membrane G-protein coupled receptors. Protease-activated receptor 1 (PAR-1) is a typical member of this family of receptors that mediate cellular responses to thrombin and related proteases. PAR1 is expressed by a wide range of tumor cells and can promote tumor growth, invasion and metastasis. The aim of this work was to study the role of PAR-1 expression in newly diagnosed ALL patients. PATIENTS AND METHODS: This study was conducted on 44 children with newly diagnosed ALL who were admitted to Hematology Unit, Pediatric department, Tanta University Hospital including 24 males and 20 females with their age ranged from 4-17 years and their mean age value of 9.06±3.26. All patients were subjected to complete history taking, thorough clinical examination, bone marrow aspiration and flow cytometric analysis for detection of PAR-1 expression by malignant cells. RESULTS: PAR-1 was positive in 18 cases (41%) and negative in 26 cases (59%) of studied patients. This study showed no significant relation between PAR-1 expression and age, sex and most of the clinical data including hepatomegaly, splenomegaly and purpura while generalized lymphadenopathy was significantly higher in PAR-1 positive group. PAR-1 positive expression was associated with some bad prognostic laboratory parameters including higher hemoglobin, higher white blood cells, higher peripheral blood and bone marrow blast cells, higher serum LDH and lower platelets count. No significant association was detected between PAR-1 expression and immunophenotyping. There were significantly higher remission rates in PAR-1 negative group and significantly higher relapse and death rates in PAR-1 positive group. CONCLUSION: From this study, it could be concluded that PAR-1 expression on ALL cells represents an important adverse prognostic factor. RECOMMENDATIONS: PAR-1 expression should be routinely investigated for better prognostic assessment of ALL patients at diagnosis and should be taken in consideration in designing future therapeutic strategies based on patients- specific risk factors.

HLA-G expression as a prognostic indicator in B-cell chronic lymphocytic leukemia.

BACKGROUND: The expression of human leukocyte antigen (HLA)-G was studied in certain malignancies and its role in escaping from immunosurveillance in cancers was proposed since HLA-G is a non-conventional HLA class I molecule that protects the fetus from immunorecognition during pregnancy. Some particles involved in the regulation of an immune system might represent prognostic value for B-cell chronic lymphocytic leukemia (B-CLL). The identification of novel prognostic factors in B-CLL may help define patient subgroups that may benefit from early therapeutic intervention. OBJECTIVE: To evaluate the prognostic significance of HLA-G expression in B-CLL patients and its relationship with other well-established prognostic markers. METHODOLOGY: Thirty B-CLL patients diagnosed by clinical, morphological and immunophenotyping criteria were studied for HLA-G expression by flow cytometry. The relationship between HLA-G expression and some known prognostic markers was evaluated. RESULTS: HLA-G was expressed in 36.7% of CLL patients at diagnosis, with a mean expression level of 35.31 ± 12.35%. A significant association between HLA-G expression and common prognostic markers of progressive disease was detected. The group of patients with positive HLA-G expression showed significantly higher absolute lymphocyte counts and serum levels of LDH and ß2-microglobulin, lower platelet counts, positive CD38 expression and advanced stages of Binet clinical staging. CONCLUSION: The present study demonstrated that HLA-G expression correlates with prognostic markers of a poor B-CLL outcome, mainly Binet clinical staging and CD38 expression by B-CLL cells, which indicates that this parameter may play a role as an important prognosticator of disease progression and consequently targeted therapy in B-CLL.

Effect of iron deficiency anemia and its treatment on cell mediated immunity.

Iron deficiency anemia (IDA) is one of the most prevalent micronutrient deficiencies particularly in the developing countries. While there is evidence of an altered immune profile in iron deficiency, the exact immunoregulatory role of iron is not known. Knowledge particularly in children, who are vulnerable to iron deficiency and infection, is lacking. We aimed to study the effects of IDA and its treatment with oral iron supplementation on cell-mediated immunity. The levels of T-lymphocytes, their CD4(+), CD8(+) and CD1a(+) subsets, transferrin receptor (CD71) and serum ferritin were evaluated in 40 iron-deficient and 40 healthy children. The impact of oral iron supplementation for three months on the same parameters was also noted in children with IDA. The level of mature T-lymphocytes (CD4(+) and CD8(+)) was significantly lower (P<0.001) while that of the immature T-cells (CD1a(+)) was significantly higher (p<0.001) in IDA children compared to the control. The mature T-cell count was significantly improved after iron therapy. In spite of significant reduction in the immature T-cells (CD1a(+)) level after iron supplementation, it was significantly higher than the control. The present study demonstrated that T-lymphocytes maturation was defective in IDA and improved partially after 3 months of iron supplementation. Therefore, longer time of iron therapy may be required to induce complete maturation of T-lymphocytes.