Late onset neonatal sepsis: Can plasma gelsolin be a promising diagnostic marker?

Plasma gelsolin (pGSN) correlates with clinical improvement in septic patients. We aimed to investigate pGSN levels as a diagnostic and prognostic marker of neonatal late-onset-sepsis (LOS). A case-control study was done on 184 neonates (92 with LOS and 92 controls). All participants were subjected to detailed history taking, full clinical evaluation, sepsis workup, and pGSN enzyme-linked immunosorbent-assay measurement. We detected significantly lower pGSN level among cases compared to controls (90.63 ±â€…20.64 vs 451.83 ±â€…209.59). It was significantly related to the severity of sepsis and mortality, with significantly lower values among cases with septic shock and multiorgan failure and non-survivors. Follow-up pGSN significantly increased after sepsis improvement in survivors compared to admission values. pGSN might be a reliable diagnostic and prognostic marker for LOS.

Genetic variant of endothelial protein C receptor genes and its serum level in B thalassemic children.

BACKGROUND: Due to their chronic hypercoagulable status, thalassemic individuals are at an elevated risk of developing thromboembolic sequence consequences. The goal of the current study is to assesses the EPCR gene polymorphism and soluble EPCR in Egyptian thalassemic children and its role in hypercoagulable state. RESEARCH DESIGN AND METHODS: Eighty children diagnosed as thalassemia major and 80 healthy youngsters as a control group. The EPCR gene was identified using a restriction fragment length polymerase chain reaction (RFLP PCR). Additionally, we assessed the soluble EPCR levels using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Frequency of 1651C-G EPCR, the GC genotype was strongly related with an increased risk of coagulation (OR = 1.83 (0.64-5.26), P = 0.0.016). In addition, soluble EPCR was considerably higher in patients with thalassemia than in controls, P value <0.001. Our study revealed significance difference between soluble EPCR and different genotypes. CONCLUSION: Polymorphisms in the EPCR gene and an elevated soluble EPCR level in patients with ß-thalassemia major may contribute to these patients' hemostatic derangement in thalassemic Egyptian children.

Vitamin D status and healthy Egyptian adolescents: Where do we stand?

ABSTRACT: Vitamin D deficiency is a worldwide public health problem. Low vitamin D and its consequences among children and adolescents could be considered as one of the most important health-related problems. This study aimed to estimate the prevalence of vitamin D deficiency in healthy Egyptian adolescents and investigate factors associated with vitamin D status.A cross-sectional study was conducted on 572 school children (270 males and 302 females) aged 14 to 18 years, who were randomly selected from high schools in one governorate in Egypt. Data were collected through a self-administered questionnaire. Vitamin D level, serum calcium, phosphorus, alkaline phosphates were measured.Vitamin D deficiency was almost present in all the studied Egyptian healthy adolescents (99%), 94.8% had vitamin D deficiency and 4.2% had vitamin D insufficiency. Girls had a higher prevalence of vitamin D deficiency than boys. There was a significant association between lack of physical activity, sun exposure, and vitamin D deficiency.Vitamin D deficiency and insufficiency are highly prevalent. In sunny countries, the special pattern of conservative clothing and the lack of outdoor physical activity might be the underlying factors for the high prevalence in females. Vitamin D supplementation seems to be mandatory to halt the problem.

Serum endocan and endothelial dysfunction in childhood acute lymphoblastic leukemia survivors: a tertiary center experience.

BACKGROUND: An increased risk of cardiovascular complications is reported in survivors of childhood acute lymphoblastic leukemia (ALL). Early identification of impaired vascular health may allow for early interventions to improve outcomes. AIM: The study was conducted to assess the endothelial dysfunction in ALL survivors using a new marker, serum endocan, and measurement of the mean common carotid arteries intima media thickness (cIMT). METHODS: A case-control study was conducted on 100 childhood ALL survivors (aged 6-18 years), with 80 healthy age and sex-matched children as a control group. Lipid profile, hepatitis markers, and serum ferritin where measured, in addition to the measurement of serum endocan. and cIMT by B-mode high-resolution ultrasonography for all study participants. RESULTS: Triglycerides, total cholesterol, post prandial glucose, and serum ferritin were significantly higher in ALL survivors than controls (p < 0.05). Dyslipidemia was detected in 6% of ALL survivors. ALL survivors showed statistically higher serum endocan levels (470.41 ± 556.1 ng/l, versus, 225.94 ± 185.2 ng/l, respectively) and increased cIMT levels compared with the control group (0.650 ± 0.129 mm versus 0.320 ± 0.095 mm, respectively) p < 0.05. Serum endocan was positively correlated with cIMT and blood cholesterol. CONCLUSIONS: The survivors of childhood ALL demonstrated an elevated level of serum endocan and increased cIMT. These can be used as predictors of endothelial dysfunction, and, as a consequence, the risk of developing premature atherosclerosis.

Genetic polymorphism of vitamin D receptors and plasminogen activator inhibitor-1 and osteonecrosis risk in childhood acute lymphoblastic leukemia.

BACKGROUND: Osteonecrosis (ON) is one of the major therapy-related complications in childhood acute lymphoblastic leukemia (ALL). The purpose of the current study is to assess the frequency of ON in children with ALL and to detect whether polymorphisms in vitamin D receptor gene (VDR) and plasminogen activator inhibitor-1 (PAI-1) gene can affect the risk of ON. PATIENTS AND METHODS: Nighty-six ALL children were enrolled. Serum 25-hydroxyvitamin D 25(OH)D levels were performed in addition to the detection of polymorphisms in PAI-1and VDR genes by polymerase chain reaction. RESULTS: Ten out of 96 patients had ON (four males and six females aged above 10 years) and had an insufficient level of 25(OH)D. Fifty-two percent of patients had PAI-1 GG genotype while 48% had PAI-1 GA genotype. PAI-1 polymorphism was detected in 60% of all ON cases. The frequencies of VDR genotypes were CT (56.3%), CC (39.6%), and TT (4.2%). Osteonecrosis was found in eight patients with CC genotype and in two patients with CT genotype. CONCLUSION: Osteonecrosis can develop early during the therapy of ALL. Older age and insufficient level of 25(OH)D were considered important risk factor for the development of osteonecrosis. PAT-1 and VDR gene polymorphism may be a genetic risk factor in its pathogenesis.

Propionic and Methylmalonic Acidemias: Initial Clinical and Biochemical Presentation.

PA and MAA have numerous nonspecific presentations, potentially leading to delayed diagnosis or misdiagnosis. In this paper, we present the clinical and biochemical characteristics of MMA and PA patients at initial presentation. Results. This is a retrospective review of 20 patients with PA (n = 10) and MMA (n = 10). The most observed symptoms were vomiting (85%) and refusing feeding (70%). Ammonia was 108.75 ± 9.3 µmol/l, showing a negative correlation with pH and bicarbonate and positive correlation with lactate and anion gap. Peak ammonia did not correlate with age of onset (r = 0.11 and p = 0.64) or age at diagnosis (r = 0.39 and p = 0.089), nor did pH (r = 0.01, p = 0.96; r = -0.25, p = 0.28) or bicarbonate (r = 0.07, p = 0.76; r = -0.22, p = 0.34). There was no correlation between ammonia and C3 : C2 (r = 0.1 and p = 0.96) or C3 (r = 0.23 and p = 0.32). The glycine was 386 ± 167.1 µmol/l, and it was higher in PA (p = 0.003). There was a positive correlation between glycine and both pH (r = 0.56 and p = 0.01) and HCO3 (r = 0.49 and p = 0.026). There was no correlation between glycine and ammonia (r = -0.435 and p = 0.055) or lactate (r = 0.32 and p = 0.160). Conclusion. Clinical presentation of PA and MMA is nonspecific, though vomiting and refusing feeding are potential markers of decompensation. Blood gas, lactate, and ammonia levels are also good predictors of decompensation, though increasing levels of glycine may not indicate metabolic instability.

Factor VIII inhibitor development in Egyptian hemophilia patients: does intron 22 inversion mutation play a role?

BACKGROUND: Hemophilia A (HA) is an X-linked recessive bleeding disorder characterized by qualitative and quantitative deficiency of factor VIII (FVIII). The development of inhibitor antibodies against FVIII is the most challenging complication of treatment. Mutations in the FVIII gene is one of the genetic factors that leads to development of FVIII inhibitors especially intron 22 inversion (Inv22). OBJECTIVES: This study was carried out to assess the frequency of Inv22 of FVIII gene in Egyptian patients with hemophilia A and its role as a risk factor for developing inhibitors. PATIENTS AND METHODS: Seventy-two patients with severe HA and 48 patients with moderate HA were enrolled in the current study. All patients were treated on demand with either plasma-derived factor VIII or recombinant factor VIII concentrates. Genotyping of FVIII Inv22 was performed by LD-PCR while the presence and magnitude of inhibitor activity in blood was determined by the Bethesda assay. RESULTS: Around 23% of all hemophilia cases had positive Inv22. Intron 22 inversion mutation was detected in 6 and 33% of patients with moderate and severe HA respectively. Twenty-one cases (18%) of all hemophilic patients developed inhibitors. Thirty-7% of patients with Inv22 had inhibitor in their blood, almost all, but one, had severe HA. The risk of an inhibitor development during replacement therapy was four folds higher among Inv22 positive cases as compared with mutation negative peers (OR 4.3, 95% CI 1.6-11.9, P = 0.003). CONCLUSIONS: The prevalence of Inv22 of F VIII in Egyptian hemophiliacs is nearly like that of other population. This mutation was more frequently detected among severe hemophilic patients as compared with moderately affected peers. The presence of Inv22 mutation significantly predispose to FVIII inhibitor development.

Conventional intensive versus LED intensive phototherapy oxidative stress burden in neonatal hyperbilirubinaemia of haemolytic origin.

Background: Phototherapy causes oxidative stress which is of particular importance in neonates because of the increased susceptibility of neonatal red blood cell membranes to oxidative damage.Aim: To evaluate the oxidant/antioxidant status in neonates with haemolytic hyperbilirubinaemia before and after exposure to two different intensive phototherapy light sources.Patients and Methods: A randomised controlled study was undertaken in 54 full-term neonates with indirect haemolytic hyperbilirubinaemia admitted to a neonatal intensive care unit in the first week of life. They were randomly divided into two equal groups. Group 1 infants were exposed to intensive conventional phototherapy (Bilisphere 360) and Group 2 were exposed to an intensive light-emitting diode (LED) phototherapy device (Bilitron bed 3600). Total serum bilirubin (TSB), total oxidative stress (TOS), total antioxidant capacity (TAC) and the oxidative stress index (OSI) were measured before and 48 hours after initiation of phototherapy.Results: There was a significant decrease in TSB after phototherapy in both groups (p < 0.001). The TOS and OSI were significantly increased after phototherapy in both groups (p < 0.001) but more so in Group 1 with conventional phototherapy (p = 0.05 and 0.01, respectively). TAC was significantly decreased after phototherapy in both groups (p < 0.00) but more so in Group 1 (p = 0.03).There were significant increases in the incidence of dehydration, hyperthermia and skin rash in the conventional compared with the LED phototherapy group (p = 0.02, 0.01 and 0.02, respectively). However, there was a significant increase in the incidence of hypothermia in the LED compared with the conventional phototherapy group (p = 0.001).Conclusion: Both intensive conventional and LED phototherapy are equally effective in decreasing TSB, but intensive LED phototherapy is safer than intensive conventional phototherapy with regard to oxidative stress and oxidant/antioxidant imbalance.Abbreviations: DSB: direct serum bilirubin; G6PD: glucose-6-phosphate dehydrogenase enzyme; LED: light-emitting diode; OSI: oxidative stress index; TAC: total antioxidant capacity; TOS: total oxidative stresses; TSB: total serum bilirubin.

Maternal vitamin D level and vitamin D receptor gene polymorphism as a risk factor for congenital heart diseases in offspring; An Egyptian case-control study.

Vitamin D & vitamin D receptor (VDR) signaling play a very crucial role in early embryonic heart development. We construct this case-control study to investigate the association between maternal serum vitamin D level & VDR gene Fok1 polymorphism and risk of congenital heart defects (CHD) in offspring. Fifty mothers who had term neonates with CHD were considered as cases. Fifty age-comparable healthy mothers who had neonates without CHD were contemplated as controls. Maternal serum 25 hydroxyvitamin D [25(OH) D] level was tested using ELISA. Maternal VDR gene Fok1 polymorphism was analyzed using PCR-based RFLP-assay. There was a significant decrease in maternal vitamin D level (P = 0.002) and a significant increase in vitamin D deficient status (P = 0.007) among cases when compared to controls. VDR gene Fok1 genotypes distribution frequency were in accordance with Hardy Weinberg equilibrium (HW) among controls. A significant increase in VDR gene Fok1 F/f & f/f genotypes and f allele were observed in cases compared to controls with estimated odds ratio (95% confidence interval) & P-value of 3 (1-8) & P = 0.006, 11 (1-97) & P = 0.01 and 3 (2-6) & P = 0.001 respectively. There was a significant decrease in maternal vitamin D level in neonates with cyanotic CHD (P = 0.000) compared to those with a cyanotic CHD while there was no significant difference in VDR Fok1 genotype (P = 0.18) & allele (P = 0.05) distribution between two groups. We concluded that maternal vitamin D deficiency and VDR gene Fok1 F/f, f/f genotype and f allele were associated with increased risk of CHD in offspring.

Does implementing a regime of dexamethasone before planned cesarean section at term reduce admission with respiratory morbidity to neonatal intensive care unit? A randomized controlled trial.

AIM: To assess the effectiveness of dexamethasone before planned cesarean section (CS) at term in reducing admission with respiratory morbidity to neonatal intensive care units (NICU). METHODS: A prospective randomized controlled trial which was conducted at an Egyptian teaching hospital. Participants at ≥38 weeks gestation who were planned to have planned CS were recruited. They were randomized into a treatment group (636 women) who received three intramuscular (IM) doses of dexamethasone 8 mg, 8 h apart, and control group (636 women) who have not received dexamethasone, before having planned CS. The primary outcome was admission to NICU with respiratory morbidity, which was analyzed by intention to treat. RESULTS: A total of 1272 planned CS's were carried out in this trial. They were associated with less admission to NICU with respiratory morbidity in women treated with dexamethasone than in women not treated (13 (2.0%) versus 21 (3.3%), respectively). However, the difference between the two groups failed to show a statistical significance (p = .88). CONCLUSION: Dexamethasone administration before planned CS at term, as compared to routine management without antenatal steroids, was not associated with a statistically significant reduction in the incidence of admission to NICU with respiratory morbidity.

Premature atherosclerosis in children with beta-thalassemia major: New diagnostic marker.

BACKGROUND: Early vascular alteration, atherosclerosis and coronary artery disease have emerged as important cardiovascular complications among beta-thalassemia major (B-TM) patients. The aims of the current study were to assess the prevalence of premature atherosclerosis among our B-TM patients, and to investigate the diagnostic value of serum Osteoprotegerin assay as an early biomarker for atherosclerosis. METHODS: This cross-sectional study was conducted at Hematology unit - Pediatric Department, Zagazig University Children Hospital- Egypt in the period from March 2014 to March 2015. A total of 115 children were enrolled in the current study; as sixty-five (65) children with beta thalassemia major aged 5-18 years, on regular blood transfusion regimen represented the patient group. While fifty (50) healthy children, with comparable age and gender, were assigned as control group. All participants were subjected to history taking, thorough clinical examination and laboratory investigations including; complete blood count, liver and kidney function tests, C- reactive protein, lipid profile, serum ferritin and serum Osteoprotegerin (OPG) assay. Also, carotid artery intima media thickness (CAIMT) was performed by duplex ultrasound for patients and controls. RESULTS: Our B-TM patients were transfusion-dependent for as long as 8.5 ± 3.8 years with significantly higher serum ferritin levels (2490 ± 1579 ng/dl vs 83 ± 32 ng/dl, p = 0.001), C-reactive protein (5.7 ± 5.7 vs 0.9 ± 0.9), liver enzymes and bilirubin when compared to controls. Significantly higher serum triglyceride (128 ± 20 vs 101 ± 7 mg/dL, p = 0.009) and atherogenic index of plasma (0.45 ± 0.12 vs 0.22 ± 0.04, p = 0.001) were recorded in patients than comparisons. On the contrary, total serum cholesterol (116 ± 16 vs 143 ± 5, p < 0.001), low density lipoprotein-cholesterol (LDL-C) (44 ± 9 vs 73 ± 6, p < 0.001) and high density lipoprotein cholesterol (HDL-C) (39 ± 2 vs 61 ± 5, p < 0.001), were significantly lowered in patients versus normal peers. Carotid arteries intima media thickness (CAIMT) of both side were significantly increased for patients (Rt 0.62 ± 0.2 vs. 0.29 ± 0.07 mm, p = 0.001 & Lt 0.66 ± 0.17 vs 0.29 ± 0.05 mm, p = 0.001) when compared with healthy controls, and showed positive correlation with, serum triglyceride, atherogenic index of plasma, and serum Osteoprotegerin levels. ELISA assay of serum Osteoprotegerin (OPG) revealed significantly higher levels for thalassemia patients than matched healthy controls (427 ± 102 vs. 324 ± 126 pg/ml, p = 0.02). Of particular interest is the obvious positive correlation between OPG levels and CAIMT of both sides (Rt r 0.54, p = 0.001 &Lt r 0.479, p = 0.001) and also with serum triglycerides (r 0.374, p = 0.03). CONCLUSIONS: Subclinical atherosclerosis started prematurely in children with beta- thalassemia. Carotid artery intima media thickness represented a simple, accurate and non-invasivemodality for early detection ofatherosclerosis. It was correlated well with serum Osteoprotegerin; this finding highlighted the possible validity of OPG assay as an early predictor of atherosclerosis in thalassemia children.

Reducing ventilator-associated pneumonia in neonatal intensive care unit using "VAP prevention Bundle": a cohort study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a serious health care-associated infection, resulting in high morbidity and mortality. It also prolongs hospital stay and drives up hospital costs. Measures employed in preventing ventilator-associated pneumonia in developing countries are rarely reported. In this study we tried to assess the efficacy of our designed "VAP prevention bundle" in reducing VAP rate in our neonatal intensive care unit (NICU). METHOD: This prospective before-and-after study was conducted at university hospital NICU, all neonates who had mechanical ventilation for ≥ 48 h were eligible. VAP rates were evaluated before (phase-I) and after (phase-II) full implementation of comprehensive preventive measures specifically designed by our infection control team. RESULTS: Of 143 mechanically ventilated neonates, 73 patients developed VAP (51%) throughout the study period (2500 mechanical ventilation days). The rate of VAP was significantly reduced from 67.8% (42/62) corresponding to 36.4 VAP episodes/1000 mechanical ventilation days (MV days) in phase-I to 38.2% (31/81) corresponding to 23 VAP/1000 MV days (RR 0.565, 95% confidence interval 0.408-0.782, p = 0.0006) after VAP prevention bundle implementation (phase-II). Parallel significant reduction in MV days/case were documented in post-intervention period (21.50 ± 7.6 days in phase-I versus 10.36 ± 5.2 days in phase-II, p = 0.000). There were a trend toward reduction in NICU length of stay (23.9 ± 10.3 versus 22.8 ± 9.6 days, p = 0.56) and overall mortality (25% versus 17.3%, p = 0.215) between the two phases but didn't reach statistical significance. The commonest micro-organisms isolated throughout the study were gram-negative bacteria (63/66, 95.5%) particularly Klebsilla pneumonia (55/66, 83.4%). CONCLUSION: Implementation of multifaceted infection control bundle resulted in reduction of VAP rate, length of stay in our NICU.