Long noncoding RNAs (CTC-471J1.2, NeST) as epigenetic risk factors of active juvenile lupus nephritis: a case-control study.

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.

Virtual Surgical Guidance Improves Quality of Life Following Scapular Free-Flap Reconstruction of Maxillary Defects.

BACKGROUND: The best approach to maxillary reconstruction with negative impact on the patient's quality of life (QOL) remains the subject of debate. PURPOSE: This study was designed to evaluate the QOL outcomes following maxillary reconstruction using a scapular-free flap, with and without the computer-aided design and computer-aided manufacturing (CAD/CAM) technique. STUDY DESIGN, SETTING, SAMPLE: A prospective randomized controlled clinical trial was performed following the CONSORT checklist. To be included, patients suffering from maxillary defects without previous surgery or lymph node involvement were selected. Patients with poor oncological prognosis, deficient performance status, preoperative chemotherapy, or radiotherapy, besides vascular contraindications, were excluded. PREDICTOR VARIABLE: The predictor variable was the reconstruction technique, grouped into two equal categories. Patients were randomly assigned to reconstruction with a scapular-free flap, with the control group not utilizing a guide and the study group utilizing a CAD/CAM-customized guide. MAIN OUTCOME VARIABLE: The primary outcome variable was the various domains of QOL, measured using the University of Washington Quality of Life score, 12 months after reconstruction. COVARIATES: Age; sex; scapular flap side; and maxillary defect tumour type, histopathology, side, length, class, sagittal, and axial differential areas were considered. ANALYSES: Shapiro-Wilk and Kolmogorov-Smirnov tests were performed for normality. For comparisons between the two groups, Student's t-test and Mann-Whitney test were used. The category variables were compared using the χ2 test. P ≤ .05 was considered statistically significant. RESULTS: The sample was composed of twenty-two eligible patients, eleven in each group. The mean age of the control group was (50.09 ± 17.14) years, and 45.45% were male, while in the study group, the mean age was (48.36 ± 14.14) years, with 36.36% male. All the patients were evaluated, showing statistically significant differences between control and study groups in terms of pain, appearance, chewing, swallowing, speech, and shoulder (P ≤ .05), indicating that the scapular-free flap with a CAD/CAM osteotomy guide had improved the patient's QOL. CONCLUSION AND RELEVANCE: The findings of this study indicate that virtual surgical planning with a CAD/CAM customized osteotomy guide using a scapular-free flap can improve QOL in maxillary reconstruction in terms of pain, appearance, chewing and swallowing food, pronouncing words, and shoulder QOL outcomes.

Right Ventricular Strain Analysis By Tissue Tracking Cardiac Magnetic Resonance Imaging In Pediatric Patients With End-Stage Renal Disease.

PURPOSE: To investigate right ventricular (RV) volume and mass by cardiac magnetic resonance (CMR) and the added value of tissue tracking strain analysis as markers of RV dysfunction in pediatric patients with end-stage renal disease (ESRD) and preserved RV ejection fraction. MATERIALS AND METHODS: Twenty-five children with ESRD and preserved RVEF (>50%) and 10 healthy control children were enrolled. Tissue tracking CMR was used to assess Global Longitudinal, circumferential (GCS), and radial short and long axes (GRS SAX and GRS LAX) RV strains in the patients group compared with controls. Correlations between strain parameters and other CMR parameters and clinical biomarkers were assessed. Binary logistic regression was used to test the independence of cofounders and detect their significance. RESULTS: RV end-diastolic volume and mass (RVMi) were significantly higher in patients (97.2±19.3 mL/m 2 and 26.6±7gr/m 2 ) than control (71±7.8 mL/m 2 and 11.9±2 gr/m 2 , P values 0.000). All RV global strain parameters were significantly impaired in patients compared with control (all P values <0.05). RV Global Longitudinal was significantly correlated to LVEF (r=-0.416, P =0.039), LVEDVi (r=0.481, P =0.015), LVMi (r=0.562, P =0.004), and systolic blood pressure index (r=0.586, P =0.002). RV GRS (LAX) was significantly correlated to LV GCS (r=-0.462, P =0.020) and LV GRS (SAX) (r=0.454, P =0.023). GRS (SAX) and GCS demonstrated the highest diagnostic accuracy (area under curve: 0.82 and 0.81) to detect strain impairment. Univariate binary logistic regression with patients versus control as dependent variables identified LVMi, RV end-diastolic volume, RVMi, weight, body surface area, RV GCS, RV GRS (LAX), RV GRS (SAX), LV GCS, and LV GRS (SAX) as significantly correlated to patients with ESRD. When adjusted to other cofounders in the multivariable model, only RVMi remained as an independent significant cofounder (Odds ratio:0.395, P =0.046). CONCLUSION: RV global strain, volume, and mass by CMR are markers of RV dysfunction in ESRD pediatric patients with preserved RVEF.

Aesthetic Reconstruction of Onco-surgical Mandibular Defects Using Free Fibular Flap with and without CAD/CAM Customized Osteotomy Guide: A Randomized Controlled Clinical Trial.

BACKGROUND: Reconstruction of mandibular defects following ablative surgery remains a challenge even for experienced surgeons. Virtual planning and guided surgery, including computer-aided design/computer-aided manufacturing (CAD/CAM), afford optimized ways by which to plan complex surgery. This study aimed to evaluate and compare aesthetic outcome and surgical efficiency of free fibular flap (FFF) with and without CAD/CAM customized osteotomy guide (COG) for reconstruction of onco-surgical mandibular defects. METHODS: Twenty-two patients indicated for segmental mandibulectomy were randomly assigned to either CAD/CAM with COG group or that without COG- Model based reconstruction (MB group) at a 1:1 ratio. Aesthetic outcomes were evaluated by means of morphometric assessment and comparison for each differential area (DAr) and angle (DAn) in the affected side to the contralateral side of the mandible using computerized digital imaging analysis (CDIA) based on the post-operative 3D CT-scan. Subjective evaluation was performed using the Visual Analogue Scale (VAS) and Patient's Satisfaction Score (PSS). Surgical efficiency was a secondary outcome and evaluated as total operative time and ischemia time. RESULTS: The mean sagittal DAr was significantly lower in the COG group (277.28 ± 127.05 vs. 398.67 ± 139.10 mm2, P = 0.045). Although there was an improvement in the axial DAr (147.61 ± 55.42 vs. 183.68 ± 72.85 mm2), the difference was not statistically significant (P = 0.206). The mean differences (Δ) in both sagittal and coronal DAn were significantly lower in the COG group than in the MB group (6.11 ± 3.46 and 1.77 ± 1.12° vs. 9.53 ± 4.17 and 3.44 ± 2.34°), respectively. There were no statistically significant differences in the axial DAn between the two groups (P = 0.386). The PSS was significantly higher in the COG group, reflecting better aesthetic satisfaction than in the MB group (P = 0.041). The total operation and ischemia time were significantly shorter in favor of the COG group with a mean of (562.91 ± 51.22, 97.55 ± 16.80 min vs. 663.55 ± 53.43, 172.45 ± 21.87 min), respectively. CONCLUSION: The CAD/CAM with COG is more reliable and highly valuable in enhancing aesthetic outcomes and surgical efficiency of mandibular reconstruction by FFF compared to that without COG (MB reconstruction). TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov . REGISTRATION NUMBER: NCT03757273. Registration date: 28/11/2018.

Primary Malignant Peripheral Nerve Sheath Tumor of the Breast: A Rare Case Report and Review of Literature.

Primary breast sarcomas are uncommon and primary mammary malignant peripheral nerve sheet tumors (MPNST) are exceptionally rare. MPNSTs are malignant variants of peripheral nerve sheath tumors. These neoplasms are often associated with neurofibromatosis type I (NF-I) but can also occur sporadically. They tend to occur in the deeper soft tissues, trunk, and extremities. A 60-year-old Asian female was referred to our surgical clinic for evaluation of a left breast mass and an abnormal mammogram. The patient noticed the mass in the left breast three months earlier and was referred for mammography by her primary physician. Mammography reported partially defined masses in the superior aspect of the left breast, and ultrasound showed a solid mass measuring 5.2 X 3 cm. The mass was 11 cm on clinical exam. Subsequent core biopsy of the left breast lesion showed high-grade malignant neoplasm. Workup showed no evidence of metastatic disease, and the patient underwent modified radical mastectomy. The neoplastic cells were positive for CD99, S-100, SOX-10, neuron specific enolase, p53, vimentin, focally positive for neurofilament, D2-40, p63, and negative for epithelial, melanoma and other sarcoma markers. The tumor was triple negative estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), with Ki-67 at 61%. A diagnosis of primary high grade malignant peripheral nerve sheath tumor of the breast was rendered. The patient does not have a history of NF-1. An accurate diagnosis of this rare entity is necessary because it plays a crucial role in the therapeutic options and prognosis. In our case the patient underwent modified radical mastectomy. The purpose of presenting this unique case is to provide awareness of the existence of this entity among pathologists and clinicians for better patient care.

Aesthetic reconstruction of onco-surgical maxillary defects using free scapular flap with and without CAD/CAM customized osteotomy guide.

BACKGROUND: Reconstruction of the maxillary defects following tumor ablation remains to be a challenge for surgeons. Virtual surgical planning (VSP), intraoperative cutting guides and stereolithographic models provides the head and neck reconstructive surgeon with powerful tools for complex reconstruction planning. Despite its use in fibular osteocutaneous reconstruction, application to the scapular free flap has not been as widely reported. The aim of this study was to compare aesthetic results and operation time of free scapular flap, with and without computer-aided design and computer-aided manufacturing (CAD/CAM) customized osteotomy guide, for reconstruction of maxillary defects. METHODS: In this prospective randomized controlled clinical trial study, we randomly assigned 22 patients with maxillary defects who were scheduled to undergo maxillary reconstruction with either free scapular flap with CAD/CAM customized osteotomy guide; study group (n = 11) or free scapular flap without CAD/CAM customized osteotomy guide; control group (n = 11). All patients were followed up for 3 months. The aesthetic outcome, operation and ischemic times were evaluated and compared. RESULTS: Aesthetic outcomes were evaluated objectively by means of differential surface area (sagittal and axial) measurement, which showed improved aesthetic outcome (contour symmetry) in the study group with a mean of (241.39 ± 113.74 mm2), compared to patients in control group with a mean of (358.70 ± 143.99 mm2). There were significant differences between the two groups (P < 0.05). Aesthetic outcomes were also evaluated subjectively by means of visual analogue scale (VAS) and patient's satisfaction score (PSS). The postoperative aesthetic appearance was better in the study group with more patients satisfied than that in control group and there were statistically significant differences (P = 0.039). The mean total operative time was 678.81 min and 777.18 min in the study group and control group respectively (P < 0.05) and the mean ischemia time was 133.18 min and 195.72 min for study group and control group respectively (P < 0.05). The ischemia time and total operative time were shorter in the study group compared to those in the control group and there were no flap losses in both groups. CONCLUSION: The use of CAD/CAM prefabricated cutting guides facilitates scapular flap molding and placement, minimizes ischemic time and operating time as well as improves aesthetic outcomes. Trial registration This trial was registered at ClinicalTrials.gov. REGISTRATION NUMBER: NCT03757286. Registration date: 28/11/2018.

Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population.

Permanent systemic inflammation is a defining feature of systemic lupus erythematosus (SLE), which affects multiple organs. Gelatinase B/matrix metalloproteinase-9 (MMP-9) is an essential protease investigated in inflammation that has been linked to SLE. The study's objective was to investigate the relationship between the rs3918249 T/C and rs17576 A/G SNPs in the MMP-9 gene with SLE. The study was conducted with 100 SLE cases and 100 age/sex-matched healthy individuals. TaqManTM SNP was used for genotyping by real time PCR on the Artus Rotor-Gene Qiagen equipment. Haplotypes (TG: OR = 0.226, 95% CI = 0.119−0.429) and (CA: OR = 0.36, 95% CI = 0.2206−0.631), both with a p-value < 0.001 were substantially linked to a lower incidence of SLE. Conversely, the risk of SLE was not associated with the individual SNPs studied. The haplotype analysis was more significant than the SNP analysis and may correlate with the decreased risk of SLE in children and adolescents in Egypt.

Predictors of recurrence of peritoneal carcinomatosis among patients with colorectal cancer following cytoreductive surgery alone versus cytoreductive surgery plus HIPEC

Background: Peritoneal carcinomatosis (PC) is a lethal regional progression in patients with colorectal cancer (CRC). Treatment with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) achieves better local control than systemic palliative chemotherapy. Objectives: To assess the efficacy on the prognosis of CRS and HIPEC compared with CRS only and to identify possible clinicopathological factors associated with the recurrence of PC. Methods: The present retrospective study included all colorectal carcinoma cases with PC subjected to CRS with or without HIPC from January 2009 to June 2018 at the National Cancer Institute (NCI), Cairo University, Cairo, Egypt. The outcome is evaluated in terms of recurrence-free survival (RFS) and its predictors. Results: Out of the 61 patients, 45 patients (73.8%) underwent CRS plus HIPEC, and 16 (26.2%) underwent CRS alone. The 1-year RFS was 55.7%, with a median of 12 months. The risk factors for recurrence identified in the univariate analysis were T4 primary tumor, high-grade, positive lymphovascular invasion (LVI), positive extracapsular nodal spread, and patients treated with CRS only, without HIPEC. In the multivariate analysis, the independent risk factors for recurrence were high grade and patients treated with CRS only. Conclusion: T4 primary tumor, high grade, positive LVI, and positive extracapsular nodal spread seemed to be important predictors of recurrence following the treatment of PC. Our study also demonstrated that the addition of HIPEC to CRS improved the RFS. (AU)

Association of CD14 genetic variants and circulating level with systemic lupus erythematosus risk in Egyptian children and adolescents.

Aim: To demonstrate whether sCD14 and CD14 (rs2569190 A/G and rs2569191 C/T) genetic variants are associated with systemic lupus erythematosus (SLE) risk, for the first time, in Egyptian pediatrics and adolescents. Materials & methods: sCD14 concentrations were determined in plasma of 95 SLE cases and 98 healthy controls using ELISA assay. Genotyping was performed using TaqMan technology. Results: sCD14 levels were elevated in SLE. Individuals with T, CT and TT genotypes in rs2569191 were of significant risk (odds ratio = 1.471-2.035, 95% CI = 1.138-3.471) and those with combined CT+TT and haplotype GT were of higher risk of SLE (odds ratio = 1.660-1.758, 95% CI = 1.003-3.106, p < 0.05). sCD14 levels and CD14 polymorphism were not correlated with SLE clinical and laboratory features. Conclusion: In SLE, sCD14 levels are associated with rs2569190 A/G. Genotype CT+TT in rs2569191 C/T and haplotype GT are associated with SLE risk in Egyptian pediatric and adolescents.

Plasma interleukin-22 level, variants in interleukin-22 gene polymorphism, and the severity of systemic lupus erythematosus among Egyptian pediatric and adolescents.

OBJECTIVES: Our purpose was to investigate, for the first time, genotypes and alleles distribution of two single nucleotide polymorphisms (SNPs) of interleukin 22 (IL-22) (rs1012356 and rs2227485) in Egyptian pediatric and adolescents with systemic lupus erythematosus (SLE) and to evaluate the plasma IL-22 levels and their association with gene polymorphism and SLE risk and severity. METHODS: The TaqMan™ SNP genotyping assay on a real-time polymerase chain reaction (PCR) system was employed to evaluate the polymorphism's genotypes. Plasma IL-22 levels were determined by using an enzyme-linked immunoabsorbent assay (ELISA). RESULTS: The frequencies and genotypes of rs2227485 and rs1012356 in IL-22 between SLE patients and controls also haplotypes formed by the same SNPs revealed no statistically significant difference (p > 0.05). Otherwise, logistic regression analysis revealed that patients carrying rs1012356 "TA + AA" genotype had increased risk for prediction of SLE activity (OR = 1.610, 95% CI = 1.339-2.760, p = 0.034) by lowering plasma IL-22 level. CONCLUSIONS: Among Egyptian pediatric and adolescents, we confirm a combined model "TA + AA" in rs1012356 (A/T) of IL-22 in regression analysis, as an independent predictor for SLE activity by lowering IL-22 plasma levels. Despite neither SNP rs2227485 A/G in IL-22 gene nor haplotypes formed by the same two SNPs (rs2227485 A/G and rs1012356 A/T) were significantly associated with the clinical and/or laboratory manifestations of SLE.

Genetic Polymorphisms in Genes Involved in the Type I Interferon System (IFIH1/MDA-5, TNFAIP3/A20, and STAT4): Association with SLE Risk in Egyptian Children and Adolescents.

PURPOSE: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune inflammatory disease that is influenced by both genetic and environmental factors and associated with dysregulation of type I interferon (INF) response. This study aimed to investigate the effects of single nucleotide polymorphisms (SNPs) of the IFIH1, TNFAIP3, and STAT4 genes in the type I INF system on SLE risk in Egyptian children and adolescents. PATIENTS AND METHODS: We recruited 94 SLE individuals and 94 healthy subjects. SNPs of IFIH1 rs3747517 C/T, TNFAIP3 rs610604 G/T, and STAT4 rs7574865 G/T were evaluated using TaqMan™ SNP genotyping assay. RESULTS: Individuals with the TT, CT+TT genotypes, and T allele of rs3747517 in the IFIH1 gene were protective for SLE patients (OR = 0.429, 95% CI = 0.191-0.962, P = 0.040), (OR = 0.685, 95% CI = 0.477-0.984, P = 0.041), and (OR = 0.705, 95% CI = 0.527-0.944, P = 0.019), respectively. Also, individuals with the TT, GT+TT genotypes, and T allele of rs7574865 in the STAT4 gene were associated with SLE risk (OR = 3.945, 95% CI = 1.303-11.947, P = 0.015), (OR = 1.536, 95% CI = 1.058-2.231, P = 0.024), and (OR = 1.522, 95% CI = 1.113-2.082, P = 0.009), respectively. In the case of TNFAIP3 rs610604, no significant association of genotypes or alleles with SLE were detected, while the three SNPs did not show any significant association with the SLE clinical or laboratory features. CONCLUSION: Our findings indicated that rs3747517 in IFIH1 was protective for SLE in Egyptian children and adolescents. Moreover, rs7574865 in STAT4 not rs610604 in TNFAIP3 was associated with SLE risk.

Assessment of bone density and stability with immediately loaded dental implants with the All-on-Four technique in free vascularized fibular grafts used for mandibular reconstruction.

BACKGROUND: Following free fibula flaps (FFF) reconstruction of mandibular defects the patients need an early dental rehabilitation to regain their masticatory function and enhance their feeding and nutrition. METHODS: This study included 10 patients, with mandibular defects previously reconstructed with FFF that span the area between the two mandibular angles. They received a full arch fixed restoration supported by four implants using a pilot drilling guide to perform a flapless operation. The stability of the placed dental implants was assessed along with the changes in bone density. RESULTS: There was a statistically significant increase in stability after 3 and 6 months, and there was a decrease in density after 6 months. The patient satisfaction improved over the follow-up period. CONCLUSION: The All-on-Four technique is reliable and economic for early functional rehabilitation of resected jaws reconstructed with FFF; however, further studies are needed to investigate the changes in fibula bone density over time and with function.

Genetic variability of CYP2D6, CYP3A4 and CYP3A5 among the Egyptian population.

Aim: This study investigated major allelic variants of CYP2D6, CYP3A4 and CYP3A5 in Egyptians, an Arabic population for which there is little information regarding these important pharmacogenes. Patients & methods:CYP2D6*2, *4, *5, *10, *41 and gene copy number variation, as well as CYP3A4*22 and CYP3A5*3 were determined with commercially available TaqMan assays in 145 healthy study participants. Results: The CYP2D6 alleles identified suggest that the prevalence of poor metabolizers is low as none were found among the 145 subjects investigated. The frequency for CYP3A5 nonexpressers was 74.5% and the CYP3A4*22 allele frequency was low at 2.0%. Conclusion: These preliminary findings indicate that pharmacogene variation in Egyptians is different from those of other Middle Eastern/Arabic populations and warrants further investigation.

Clinicopathological Impact of Gene Polymorphism of Nephrin and Glucocorticoid Receptor Genes in Egyptian Children with Nonfamilial Nephrotic Syndrome.

Idiopathic nephrotic syndrome (NS) is one of the most common primary glomerular diseases in children. In this study, we investigate the association of single-nucleotide polymorphisms of nephrin gene and glucocorticoid receptor gene (NR3C1) and susceptibility to develop NS and the response to steroid therapy in 100 Egyptian children with NS using polymerase chain reaction-restriction fragment length polymorphism. We also analyzed the correlation between the genotypes and clinicopathologic features of the patients. Thirty-four patients (34%) were initial steroid nonresponders, renal biopsy findings of those patients were available, of which 22 (64.7%) showed minimal change NS and 12 (35.3%) had focal segmental glomerulosclerosis. The distribution of the genotypes was comparable between the patient and control groups, allele frequencies showed no significant difference between the patient's group and the control group. The genotypes showed no correlation with the age of onset of NS, initial steroid responsiveness, renal pathologic findings, estimated glomerular filtration rate (eGFR), and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene. These data suggested that the nephrin gene and NR3C1 gene SNPs do not affect the development of NS, initial steroid responsiveness, renal pathological lesion, eGFR, and serum albumin. However, 24-h protein in urine showed a significant association with the NR3C1 gene in Egyptian children with NS.

Effect of Everolimus versus Bone Marrow-Derived Stem Cells on Glomerular Injury in a Rat Model of Glomerulonephritis: A Preventive, Predictive and Personalized Implication.

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

Single-nucleotide polymorphisms (SNPs) of antioxidant enzymes SOD2 and GSTP1 genes and SLE risk and severity in an Egyptian pediatric population.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased oxidative stress that participates in immune dysregulation, and injury resulting in loss of immune tolerance and increased auto-antibody production. This study was designed to investigate the effects of genetic polymorphisms of the antioxidant enzymes genes that code for SOD2 (rs2758332) and GSTP1 (rs1695) on SLE risk and severity in Egyptian children and adolescents cohort from Delta region. METHODS: The frequencies of these genes polymorphic variants were compared between 100 SLE children and adolescents and 100 healthy control subjects. Single-nucleotide polymorphisms (SNPs) of the two antioxidants were determined using TaqMan SNP genotyping assay. RESULTS: Individuals with the TT and CT genotypes of rs2758332 in the SOD2 gene were of significant risk for SLE patients (OR = 1.831, 95% CI = 1.082-3.101, P = 0.024) and (OR = 1.864, 95% CI = 1.136-3.059, P = 0.014), respectively. Cases who have combined CT + TT genotype were of significant higher risk of SLE (OR = 1.851, 95% CI = 1.156 - 2.962, P = 0.010). While, they did not show any significant association between SOD2 genotypes or alleles with SLE clinical features. In case of the SNP rs1695 in the GSTP1 gene, no significant associations of genotypes or alleles with SLE risk or with SLE clinical features were detected. CONCLUSIONS: This study among Egyptian children and adolescents showed a strong association of the SOD2 rs2758332 not GSTP1 rs1695 polymorphism with the risk of SLE disease.

The contralateral based submental island flap for reconstruction of tongue and floor of mouth defects: Reliability and oncological outcome.

BACKGROUND: Submental artery island flap (SIF) is a viable alternative to free flaps for selected oral-cavity defects, however, concerns about its oncologic safety still exists. A novel harvesting technique and its outcome is described in here. METHODS: This is a prospective study for patients with lateralized oral tongue and/or floor of mouth (FOM) cancers who undergone reconstruction using pedicled SIF based on contralateral submental vessels (CSIF) following resection. RESULTS: Forty-one patients were included. Twenty-four patients had T2, 13 had T3, and 4 had T1 tumors. The largest flap skin paddle was 15 × 9 cm. One patient sustained complete and five sustained partial flap loss. Three patients developed tongue tethering. Median follow-up was 13.6 months. Locoregional recurrence occurred in 11 patients (26.8%); 6 oral-cavity recurrences (14.6%), 6 ipsilateral, and 1 contralateral neck recurrences (2.4%). CONCLUSION: CSIF is a reliable flap that addresses the oncologic controversy and overcomes the disadvantages of ipsilateral flap.

Postdiarrheal hemolytic uremic syndrome in Egyptian children: An 11-year single-center experience.

Hemolytic-uremic syndrome (HUS) is a leading cause of childhood acute kidney injury (AKI) worldwide, with its postdiarrheal (D+HUS) form being the most common. Scarce data are available regarding D+HUS epidemiology from developing countries. This study aims to reveal the characterization of D+ HUS in Egyptian children. This is a retrospective study of all children with D+HUS admitted to a tertiary pediatric hospital in Egypt between 2007 and 2017. The study included epidemiological, clinical and laboratory data; management details; and outcomes. A cohort of 132 children aged 4months to 12 years was analyzed. Yearly incidence peaked in 2017, and spring showed the highest peak. All cases had a diarrheal prodrome that was bloody in 83% of the cases. Edema and decreased urine output were the most frequent presentations (50.3% and 42.4%, respectively). Escherichia coli was detected in 56 cases. Dialysis was performed in 102 cases. Eight patients died during acute illness, while five patients experienced long-term sequels. Lactate dehydrogenase (LDH) positively correlated with serum creatinine and negatively correlated with reticulocytic count. Univariate analysis showed that longer anuria duration, short duration between diarrheal illness and development of AKI (P = 0.001), leukocyte count above 20 × 109 cells/L (P ≤ 0.001), platelet count below 30 × 109 cells/L (P = 0.02), high LDH levels (P = 0.02) and hematocrit above 30% (P = 0.0001), need for dialysis (P = 0.03), and neurological involvement (P ≤ 0.001) were associated with unfavorable outcomes. This is the first report with a detailed insight into the epidemiology of D+HUS in Egyptian children. The incidence of D+HUS is increasing in our country due to increased awareness of the disease and the poor public health measures. Anuria duration, leukocyte count, and neurological involvement are predictors of poor outcome in the current work, and LDH is introduced as a marker of disease severity.

Effect of tranilast in comparison with beclomethasone in chronic murine model of asthma.

AIM OF THE STUDY: The current investigation was taken to scrutinize the action of tranilast on the airway remodeling in chronic asthma in mice. MATERIALS AND METHODS: Intraperitoneal injection of ovalbumin was applied to mice for sensitization and subsequent inhalation of 1% ovalbumin three times week for 10 weeks for challenge. Beclomethasone or tranilast were given daily for the 10 week challenge period. At the end of the study, lung weight index, total collagen content, bronchoalveolar lavage level of total and differential cell counts, interleukin-13, in addition to lung tissue nitrate/nitrite and transforming growth beta-1 were measured. Also, histological analysis was done. RESULTS: Asthmatic mice demonstrated apparent fibrotic changes. Significant airway fibrosis was demonstrated by hyperplasia of goblet cells and thickening of airway epithelium, increased content of lung collagen, lung and bronchoalveolar lavage of transforming growth factor beta-1 and interleukin-13 mutually accompanied by reduction in nitrate/nitrite generation. CONCLUSIONS: Beclomethasone influence on airway remodeling was mediated mainly via suppression of eosinophilic recruitment into the airways and reduction of interleukin-13 cytokine levels. Whereas, tranilast effects on airway remodeling was found to be mainly mediated via its inhibitory effect on transforming growth beta-1. Both beclomethasone and tranilast influence airway remodeling by different degrees and mechanisms.

Airway Inflammatory Biomarker: Could It Tailor the Right Medications for the Right Asthmatic Patient?

Asthma is a heterogeneous disease, in which asthmatic patients present with different clinical phenotypes, variable endotypes, and different response to asthma medicines. Thus, we are faced with an asthma paradox; asthma is diagnosed subjectively by clinical history and treated with biologically active drugs. To solve this paradox, we need objective airway biomarkers to tailor the proper medications to the proper patient. Biomarkers should have one or more of the following characteristics:1) A biomarker that could differentiate poor symptoms perceivers from over perceivers, 2) A biomarker that could predict disease activity and hence disease outcome, 3) A biomarker that could clarify responders from non-responders asthma phenotypes, and finally 4) A biomarker that could characterize different clinical asthma phenotypes. In conclusion, we have conducted a review of literature trying to apply those four parameters to different airway inflammatory biomarkers. We found that FeNO fulfilled the four proposed clinical parameters of airway inflammatory biomarkers whereas; serum periostin was the single best systemic biomarker of airway luminal and tissue eosinophilia in severe uncontrolled TH2 asthma phenotype. Thus, this may be considered a trial towards tailoring the proper medication to the proper patient. However, application of biomarkers in clinical practice requires easier and cheaper techniques together with standardized methods for sample collection and analysis.