Egyptian Patients Research Articles

Evaluation of Safety and Efficacy of Emicizumab Prophylaxis in Egyptian Pediatric Patients with Hemophilia A: Single Center Cross Sectional Study.

Hemophilia A (HA) is an X-linked hereditary bleeding disorder caused by deficiency of coagulation factor VIII activity. Emicizumab is a bispecific monoclonal antibody that replaces the function of activated FVIII and prevents bleeds in patients with hemophilia A. Emicizumab is expected to reduce the risk of severe bleeds in those patients with their subsequent complications. However, data about its safety and efficacy in patients with hemophilia A is limited. We aimed to evaluate safety and efficacy of Emicizumab prophylaxis in Egyptian pediatric patients with HA. A prospective cohort study was conducted on 88 HA patient who received prophylaxis with Emicizumab. Breakthrough bleeding episodes as well as annualized bleeding rate(ABR) were reported for all patients before and after Emicizumab prophylaxis. All adverse events during prophylaxis were reported to evaluate the safety of Emicizumab. Joint bleeds were present in 94 % of the patients. 58% of them had one target joint, 36.4% had more than one target joint while 5.6% had no target joints. 17% of patients were positive for FVIII inhibitors. The median annualized joint bleeding rate (AJBR) was reduced remarkably after Emicizumab prophylaxis (36 before versus zero after Emicizumab. Also, the median ABR was 48 before Emicizumab versus zero after Emicizumab. Eight patients developed mild breakthrough bleeding episodes. The most common adverse events were local reaction at the injection sites, headache, arthralgia, fever and diarrhea. Emicizumab prophylaxis was associated with significantly lower rate of bleeding events in patients with HA with and without inhibitors. The majority of patients had zero bleeds with Emicizumab prophylaxis.

One pot multi-component synthesis of novel functionalized pyrazolo furan-2(5H)-one derivatives: in vitro, DFT, molecular docking, and pharmacophore studies, as coronavirus inhibitors.

New and facile one-pot approach for the syntheses of 12 derivatives of 3,5-disubstituted furane-2(5H)-one (4a-l) from easily available starting materials. The suitable synthetic procedures for selective synthesis of diverse furane-2(5H)-one derivatives were achieved via multi-component condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1), pyruvic acid and different aromatic amines 3a-l in good to high yields and short reaction time by refluxing in acetic acid as well as obtained by another method (method B) when unsaturated arylidene pyruvic acid 6 was refluxed with different aromatic amines in acetic acid but in smaller yield than method A. Structures of the prepared compounds were elucidated by elemental analysis and spectral data as mass, IR, 1H-NMR and 13C-NMR spectroscopy. The antiviral efficacy of compounds 4a-l against SARS-CoV-2 was evaluated using the MTT assay. It was demonstrated that synthetic compounds 4c-e and 4h-j have a potent and selective inhibitory effect on SARS-CoV-2, a strain obtained from Egyptian patients. We utilized density-functional theory (DFT) analyses to deduce the molecular structures and topologies of the more energetic molecules. Molecular docking studies were performed against the SARS-CoV-2 main protease (PDB ID: 6Y84) and the SARS-CoV-2 Nsp9 RNA binding protein (PDB ID: 6W4B) to study the binding mechanism, non-bonding interactions, and binding affinity. Lastly, a hypothetical pharmacophore model was constructed by applying the Molecular Operating Environment (MOE) tool and eleven pharmaceuticals with proven antiviral activity.

The clinical importance of IFN-γ and human epididymis protein 4 in Egyptian patients with epithelial ovarian cancer combined with HPV infection

BackgroundHigh-grade Epithelial Ovarian Cancer (HGEOC) is an aggressive disease that usually presents at an advanced stage. Thus, detecting the circulating cytokines (IFNγ and TNF-α) may serve as a biomarker to identify malignancy and manage therapeutic decisions. ObjectivesAssessing the clinical importance of inflammatory mediators and tumor markers in EOC Egyptian patients compared with benign cases. Moreover, identifying the distinct inflammatory mediators in EOC patients combined with HPV infection. MethodsThis study was conducted on 61 Egyptian patients, divided into 25 patients with HGEOC, 22 patients with LGEOC, and 14 benign ovarian tumor cases. Measurements of serum HE4, CA125, CEA, and CA19-9 were determined by Roche Elecsys immunoassays. Serum levels of TNF-α and IFN-γ were measured using quantitative sandwich ELISA. Quantitative genotyping of HPV DNA types 16, 18, and 45 was assessed for the HPV DNA-positive samples. ResultsHPV DNA was detected in 25.53 % of malignant cases, HPV 16 was detected in 50 % of HPV-positive cases, and only 1 case of HPV 18 was detected out of 12 positive cases. The Human Epididymis protein 4 (HE4) was statistically different between patients with EOC and benign cases (p-value = 0.007) and between HPV DNA positive and HPV DNA negative cases (p-value = 0.008). The serum levels of IFN- γ were statistically different between HGEOC and LGEOC (p-value < 0.001), while the serum levels of TNF-α didn’t differ statistically between the two groups. ConclusionIFN-γ could be used as a biomarker to discriminate HGEOC and LGEOC. Initial evidence for the possible association between HE4 and the progression of HPV-associated EOC was speculated.

Association of glutamine synthetase polymorphisms rs2296521, rs10911021 and rs12136955 with plasma ammonia concentration in valproic acid-treated Egyptian epilepsy patients.

The use of valproic acid (VPA) in the treatment of some psychiatric and neurological disorders such as bipolar disorder, migraines, and epilepsy is associated with hyperammonemia. However, the mechanism of this negative effect of VPA is unclear. In this study, we investigate gene glutamate-ammonia ligase (GLUL) polymorphisms for the glutamine synthetase (GS) enzyme, a key enzyme that catalyzes the removal of ammonia by incorporating it with glutamate to form glutamine, and we investigate whether it has a relationship with the emergence of hyperammonemia during VPA-based therapy. We enrolled 180 Egyptian epilepsy patients in this study. Patient history, general and neurological examination and blood samples from arm veins were taken. Real time TaqMan PCR polymorphism for three polymorphism SNPs (rs2296521, rs10911021 and rs12136955) of GLUL was done. We assessed the relationship between the patient features, including three GLUL polymorphisms, and the development of hyperammonemia during VPA-based therapy. We found that the ammonia levels showed a positive correlation with VPA treatment duration (p = 0.015) and a negative correlation with carbamazepine total dose per day (p = 0.027) and with WBCs count (p = 0.026). Also, female patients having rs2296521 SNPs with the A allele and patients having rs10911021 SNPs with the C allele were at high risk for elevated plasma ammonia levels. Moreover, patients having rs12136955 SNPs with the A allele or associated hypertension as a co-morbidity were at high risk for elevated plasma ammonia levels. Female patients who have rs2296521 with the A allele, rs10911021 with the C allele, or rs12136955 with the A allele, are independent risk factors for elevated plasma ammonia levels during VPA-based therapy. Moreover, carbamazepine combined therapy may protect against the development of hyperammonemia in VPA-treated patients.

Relation between vitamin D and COVID-19 in Egyptian patients

BackgroundInsufficient vitamin D (VD) levels have been linked to a higher vulnerability to acute respiratory infections and the severity of COVID-19 sickness.ObjectiveThe purpose of this research is to investigate whether or not there is a connection between the amounts of VD produced by patients from Egypt and the severity of COVID-19, as well as the consequences of the disease.MethodsThis research used a case–control design and included a total of 90 adult patients who had been diagnosed with COVID-19, as well as 90 healthy controls who were matched in terms of age and sex. Patients were classified into mild, moderate, and severe categories according to clinical and radiological criteria. The study included measuring levels of VD and analyzing their relationships with illness severity, inflammatory markers, radiological findings, and outcomes.ResultsCOVID-19 patient(s) had notably reduced levels of serum VD versus the control group (11.78 ± 3.24 ng/mL vs. 20.88 ± 7.76 ng/mL, p < 0.001). Lower VD levels were associated with more severe disease (p < 0.001), dyspnea (p < 0.001), radiological abnormalities (p = 0.001), and higher mortality (p < 0.001). A serum VD level ≤ 14.8 ng/mL could differentiate COVID-19 patients from controls with 86.67% sensitivity and 77.78% specificity (AUC = 0.881).ConclusionsCOVID-19 patients often had a deficiency of VD, which was linked to more severe illness, respiratory issues, aberrant radiological findings, and higher fatality rates. VD levels may be used as a biological surrogate marker to assess the risk and predict the outcome of COVID-19.

Cognitive assessment of a sample of Egyptian patients with amyotrophic lateral sclerosis

BackgroundCognitive and behavioral changes in ALS are featured as an integral part of the disease. A noticeable proportion of ALS patients present with a full-blown picture of frontotemporal dementia, which is considered the most common form of cognitive impairment in ALS.ResultsA total of 30 ALS cases and 30 sex, age and education matched healthy controls were enrolled; their sociodemographic data were statistically insignificant as regards (age, sex, education). Regarding cognitive and behavioral assessment using the ECAS-EG, both ECAS mean total score and subdomains mean scores were significantly lower in ALS patients compared to controls (p-value < 0.001), with statistically significant relation between ALS clinical staging and ECAS total scores (p-value < 0.001). Furthermore, it was found that mean scores of nearly all ECAS domains are lower in early-onset group with longer duration of illness than late onset with short duration of illness but with a non-statistically significant difference.ConclusionALS causes significant cognitive impairment, with relation between functional status and clinical staging of the disease with the severity of cognitive and behavioral dysfunctions and although early-onset cases had lower score on ECAS compared to those with late onset, but it was non-significant.

Genomic landscape of hepatocellular carcinoma in Egyptian patients by whole exome sequencing

BackgroundHepatocellular carcinoma (HCC) is the most common primary liver cancer. Chronic hepatitis and liver cirrhosis lead to accumulation of genetic alterations driving HCC pathogenesis. This study is designed to explore genomic landscape of HCC in Egyptian patients by whole exome sequencing.MethodsWhole exome sequencing using Ion Torrent was done on 13 HCC patients, who underwent surgical intervention (7 patients underwent living donor liver transplantation (LDLT) and 6 patients had surgical resection}.ResultsMutational signature was mostly S1, S5, S6, and S12 in HCC. Analysis of highly mutated genes in both HCC and Non-HCC revealed the presence of highly mutated genes in HCC (AHNAK2, MUC6, MUC16, TTN, ZNF17, FLG, MUC12, OBSCN, PDE4DIP, MUC5b, and HYDIN). Among the 26 significantly mutated HCC genes—identified across 10 genome sequencing studies—in addition to TCGA, APOB and RP1L1 showed the highest number of mutations in both HCC and Non-HCC tissues. Tier 1, Tier 2 variants in TCGA SMGs in HCC and Non-HCC (TP53, PIK3CA, CDKN2A, and BAP1). Cancer Genome Landscape analysis revealed Tier 1 and Tier 2 variants in HCC (MSH2) and in Non-HCC (KMT2D and ATM). For KEGG analysis, the significantly annotated clusters in HCC were Notch signaling, Wnt signaling, PI3K-AKT pathway, Hippo signaling, Apelin signaling, Hedgehog (Hh) signaling, and MAPK signaling, in addition to ECM-receptor interaction, focal adhesion, and calcium signaling. Tier 1 and Tier 2 variants KIT, KMT2D, NOTCH1, KMT2C, PIK3CA, KIT, SMARCA4, ATM, PTEN, MSH2, and PTCH1 were low frequency variants in both HCC and Non-HCC.ConclusionOur results are in accordance with previous studies in HCC regarding highly mutated genes, TCGA and specifically enriched pathways in HCC. Analysis for clinical interpretation of variants revealed the presence of Tier 1 and Tier 2 variants that represent potential clinically actionable targets. The use of sequencing techniques to detect structural variants and novel techniques as single cell sequencing together with multiomics transcriptomics, metagenomics will integrate the molecular pathogenesis of HCC in Egyptian patients.

Effect of immunogenetics polymorphism and expression on direct-acting antiviral drug response in chronic hepatitis C

The prevalence of HCV infection in Egypt has decreased following the introduction of direct-acting antiviral therapy. However, treatment response is influenced by various factors, particularly host immunogenetics such as IL-28B and FOXP3 polymorphisms. The current study examined the impact of SNPs in the FOXP3 gene promoter region on HCV-infected Egyptian patients, along with SNPs in the IL28B gene.This study involved 99 HCV patients who achieved SVR12 after a 12 week DAA treatment while 63 HCV patients experienced treatment failure. IL28B rs12979860 SNP was identified using real-time PCR, while IL28B rs8099917, FOXP3 rs3761548, and rs2232365 SNPs were analyzed using RFLP-PCR. Serum levels of IL28B and FOXP3 were quantified using ELISA technique in representative samples from both groups. The IL28B rs12979860 T > C (P = 0.013) and FOXP3 rs2232365 A > G polymorphisms (P = 0.008) were found to significantly increase the risk of non-response. Responders had higher IL28B serum levels (P = 0.046) and lower FOXP3 levels (P < 0.001) compared to non-responders. Regression analysis showed an association between IL28B rs12979860 and FOXP3 rs2232365 with treatment response, independent of age and gender. A predictive model was developed with 76.2% sensitivity and 91.9% specificity for estimating DAAs response in HCV patients.Our findings confirmed the IL28B rs12979860 T > C and FOXP3 rs2232365 A > G polymorphisms significantly affect DAA treatment response in HCV Egyptian patients. Lower levels of IL-28B along with higher levels of FOXP3 are linked to poor response. Our results may lead to new insights into DAA responsiveness contributing to personalized medicine and improving therapeutic decision-making for HCV patients.Graphical abstract

Evaluation of the incidence, predictors, risk assessment scores and outcomes of thromboembolism in a cohort of Egyptian NHL patients - Real World Experience

Non-Hodgkin’s Lymphoma (NHL) is the most common subtype of lymphoma. The incidence of venous thromboembolism (VTE) in aggressive NHL was estimated recently to be 11%. Several risk assessment scores and factors are available to help identify cancer patients at risk for developing VTE. Patients with a pathologically confirmed diagnosis of NHL were identified at the Oncology Center of Mansoura University. The study included 777 patients: 719 with DLBCL-NOS, 26 with Anaplastic-B-cell, and 32 with T-cell-rich-NHL. Data were retrospectively collected from electronic medical records, including clinical, radiological, and laboratory information related to VTE and NHL. The median age at NHL diagnosis was 53 years, (range: 18–98). There was a male predominance, 51.4% of the cases. At initial lymphoma diagnosis, VTE was identified in 46 (5.9%) patients, and 61 (7.9%) patients experienced VTE while undergoing chemotherapy. According to logistic regression analysis, a PS (performance status) ≥ 2, bulky lesions, and mediastinal masses were significant predictors of VTE at presentation, with P-values of 0.022, 0.002, and < 0.001, respectively. Meanwhile, NHL patients who developed VTE during chemotherapy had significantly poorer PS, higher absolute neutrophilic counts (ANC), neutrophil/lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lactate dehydrogenase (LDH) levels than lymphoma patients without VTE, with P-values of 0.003, 0.034, 0.049, 0.01 and 0.007, respectively, as determined by multivariate analysis. The ROC curve identified the cut-off values of 4.875 × 109/L for ANC, 2.985 for NLR, 144.85 for PLR, and 417.5 U/L for LDH as potential markers for predicting VTE in NHL patients. Patients with a PS ≥ 2 and values exceeding these cut-offs for ANC, NLR, and PLR experienced significantly higher incidences of VTE than other groups, with P-values of 0.003, < 0.001, < 0.001, and < 0.001, respectively. At the end of the follow-up, the overall survival was significantly shortened by VTE occurring during chemotherapy, hypoalbuminemia, intermediate-high and high international prognostic index (IPI) scores (intermediate-high and high), responses other than CR and relapse, all with P-values < 0.05. ECOG PS and Inflammatory markers such as NLR, PLR, and neutrophilic count could serve as predictors of the development of thrombotic events in patients with NHL-DLBCL. Additionally, the occurrence of VTE during chemotherapy is an independent poor prognostic marker for overall survival (OS).

MiR-146a (rs2910164) Gene Polymorphism and Its Impact on Circulating MiR-146a Levels in Patients with Inflammatory Bowel Diseases.

MicroRNA-146a (miR-146a) has been involved in the pathophysiology of inflammatory bowel disease (IBD). However, the precise processes are still not entirely understood. Contradictory studies suggest that miR-146a expression could be influenced by the miR-146a rs2910164 C > G polymorphism. This case-control study aimed to investigate the association ofmiR-146a rs2910164 C > G gene polymorphism and its impact on circulating miR-146a expression levels in Egyptian IBD patients. We included 40 IBD patients and 30 matched healthy controls. Genotyping of miR-146a rs2910164 polymorphism and assessment of miR-146a expression level were done using quantitative real-time PCR in all participants. MiR-146a rs2910164 GG genotype and the G allele were reported in 47% and 70% of the IBD patient group, respectively. And they were associated with increased IBD risk. All the IBD patients with the CC genotype (100%) and most of those with the CG genotype (66.67%) had an inactive disease, while most IBD patients with the GG genotype (73.68%) had an active disease. The miR-146a expression level was the highest with the CC genotype and the lowest with the GG genotype. Also, miR-146a expression level decreased significantly in IBD patients than controls and with disease activity. Combined detection of fecal calprotectin with miR-146a expression level improved the diagnostic sensitivity and the negative predictive value in differentiating IBD patients with active disease from those inactive.Our study identified a strong association of miR-146a rs2910164 GG genotype and G allele with IBD-increased susceptibility and activity in the Egyptian population. The miR-146a rs2910164 polymorphism can reduce miR-146a expression levels in these patients as well. Further research on a larger sample size and different ethnic populations can be the key to progress in establishing this genetic association.

National Recommendations for Pharmacoeconomic Evaluations Reporting for Reimbursement and Procurement of New Pharmaceutical Applications in Egypt.

To improve resource allocation within our healthcare system, the Egyptian Authority for Unified Procurement, Medical Supply and the Management of Medical Technology (UPA) and Universal Health Insurance Authority (UHIA) established a joint economic evaluation process to support UHIA reimbursement decisions and UPA procurement decisions. The main objective of this study is to describe the developed national pharmacoeconomic guidelines in Egypt, especially for reimbursement and procurement for new pharmaceuticals. A focus group was formed as a national initiative activity by governmental authorities in Egypt. The aim of this focus group was to develop national pharmacoeconomic guidelines for the evaluation of innovative and high-budget pharmaceutical products. This group consisted of various stakeholders with experience in health economics, outcomes research, public health, and pharmacy practice. To develop our national pharmacoeconomic guidelines, three steps were taken. First, the focus group reviewed the European Network for Health Technology Assessment (EUnetHTA) methods for health economic evaluations for new pharmaceuticals as well as the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines and the Academy of Managed Care Pharmacy (AMCP) Format for Formulary Submissions. Second, the focus group used the EUnetHTA guideline as a reference and adapted it to our local context. The focus group added the value assessment component, using the CADTH and AMCP guidelines. Third, the focus group collected input and feedback from key stakeholders through a focus group by using the quasi-Delphi panel approach. The results of the focus group are a main structure of national pharmacoeconomic guidelines for the evaluation of innovative and high-budget pharmaceutical products, consisting of seven main topics. Economic evaluation is a core element of Health Technology Assessment, (HTA); therefore, the UHIA and UPA were encouraged to produce unified joint pharmacoeconomic guidelines for innovative products as an initial step in their commitment to implement the use of HTA in decision-making. This standardization of guidelines not only ensures transparency but also guarantees an accurate and transparent process to support evidence-based decision-making. These guidelines are expected to help decision-makers improve their process and attain better health outcomes for Egyptian patients.

Demographic and Characteristics of Primary Headache in Egyptian Epileptic Patients

Demographic and Characteristics of Primary Headache in Egyptian Epileptic Patients

Serum Fibroblast Growth Factor 21 as a Marker of Pre-diabetes in Obese Egyptian Patients

Serum Fibroblast Growth Factor 21 as a Marker of Pre-diabetes in Obese Egyptian Patients

The evaluation of IL-4 VNTR intron 3 and TNF-α (rs1799964) gene polymorphisms in Egyptian patients with alopecia areata: a case–control study

BackgroundAlopecia areata (AA) is a non-scarring hair loss condition that usually affects the scalp. The exact pathogenesis is poorly understood; however, multiple factors like genetics, environmental, psychological, and immunological factors may have a role. The purpose of this study was to look into possible links between the functional interleukin-4 (IL-4) gene intron 3 variable number of tandem repeats (VNTR) and TNF-(rs1799964) gene polymorphism and AA susceptibility. This case–control study consisted of 79 unrelated patients and 156 age- and sex-matched healthy individuals as a control group. The Severity of Alopecia Tool was used to assess the extent of hair loss from the scalp. Polymerase chain reaction (PCR) with specific primers was used to determine IL-4 gene 70-bp VNTR polymorphism while polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) was used to investigate TNF-α (rs1799964) gene polymorphism.ResultsNone of the selected polymorphisms for both genotypes and alleles had statistical significance when patients and controls were compared with each other (p-values for IL-4 VNTR were 0.11, 0.74, 0.052 and 0.27 and for TNF-α polymorphism was 0.71, 0.43, 0.65 and 0.55, respectively, for codominant, dominant, recessive and overdominant models of inheritance, respectively). Furthermore, the same results were retrieved when the genotypes were compared with the patient’s clinical and demographic data (p-value > 0.05).ConclusionThe findings indicate that IL-4 VNTR intron 3 and TNF-α (rs1799964) gene polymorphisms are not linked to the development of AA in the Egyptian population.

Predictors of short-term mortality in cardiogenic shock: insights from an Egyptian multicenter registry

BackgroundCardiogenic shock (CS) remains a major cause of morbidity and mortality, particularly in developing countries where there are limited resources and a lack of data on CS outcomes. This study aimed to investigate 30-day all-cause mortality in Egyptian patients with CS at tertiary referral centers.ResultsThis prospective, observational multicenter registry analyzed 16,681 patients from six cardiac centers, to evaluate the incidence, causes and predictors of CS-related mortality. Among the 529 diagnosed CS patients, 68.2% had an ischemic etiology. No discernable variations were observed in clinical or laboratory features, as well as mortality rates, between ischemic and non-ischemic CS patients. Within 30 days, 210 deaths (39.7%) occurred. Non-survivors with ischemic CS had a higher prevalence of diabetes, worsening renal function, and were more likely to receive multiple inotropes. Mortality did not significantly differ between acute coronary syndrome patients with ST elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (42.7% vs. 43.7%, p < 0.887). However, anterior STEMI patients had significantly higher mortality than those with inferior STEMI (49.5% vs. 21.6%, p < 0.003). Multivariate regression analysis identified predictors of mortality in CS, including the median hospital stay duration, leucocyte count, alanine transaminase levels, highest creatinine levels, resuscitated cardiac arrest, and use of norepinephrine, epinephrine, and dopamine.ConclusionIn an Egyptian cohort, CS incidence was 3.17%, with no mortality difference based on the underlying etiology. Independent predictors of 30-day all-cause mortality included worsening renal function, leucocyte count, resuscitated cardiac arrest, and use of multiple inotropes/vasopressors.Graphical abstract

Impact of cerebral microbleeds on bleeding and outcome after stroke thrombolysis

BackgroundCerebral microbleeds may be responsible for bleeding and poor functional outcome following thrombolysis of acute ischemic stroke. We tried to assess the association between cerebral microbleeds, hemorrhagic complication and functional outcome following intravenous thrombolysis in Egyptian acute ischemic stroke patients. We evaluated 66 acute ischemic stroke patients treated with intravenous thrombolysis for cerebral microbleeds using T2* weighted Magnetic Resonance Imaging Gradient echo. Distribution, number, and predictors of microbleeds were assessed. The effect of microbleeds presence and burden on development of hemorrhage after thrombolysis and 90 days functional outcome was evaluated.ResultsOut of 66 stroke patients treated with intravenous thrombolysis, 33 patients had microbleeds. Multivariate analysis shows that hypertension, diabetes mellitus, atrial fibrillation, smoking and leukoaraiosis were independently associated with microbleeds. Post-thrombolysis symptomatic intracerebral hemorrhage occurred in 12/66 (18.1%). Multivariate analysis shows that high burden microbleeds (≥ 10), leukoaraiosis, stroke severity, delayed thrombolysis were independently associated with intracerebral hemorrhage. Post-thrombolysis hemorrhage was statistically higher in microbleeds group (51.5%) than non-microbleeds group (9.1%) (p < 0.001). Parenchymal hemorrhage represents (58.8%) of hemorrhagic cases in microbleeds group in comparison to (33.3%) of non-microbleeds group (p = 0.62). Parenchymal hemorrhage represents (50%) of hemorrhagic cases with microbleeds < 10, while it represents (100%) of hemorrhagic cases with microbleeds ≥ 10. Favorable modified Rankin Scale (0–2) was more prevalent in non-microbleeds group (72.7%) than microbleeds group (45.5%) at 90 days (p = 0.024). Favorable outcome at discharge and at 90 days was statistically more prevalent in patients with microbleeds < 10 (p = 0.004).ConclusionHigh burden cerebral microbleeds should be considered a risk for parenchymal hemorrhage following intravenous thrombolysis. The presence and burden of microbleeds may affect prognosis 90 days after thrombolytic therapy.

Association of PLCE1 (rs7922612) and COL4A3 (rs375290088) Genetic Variants with the Risk of Nephrotic Syndrome in Egyptian Pediatric Patients.

Nephrotic syndrome is one of the most prevalent pediatric kidney illnesses seen in pediatric nephrology clinics. Steroid resistance in children with nephrotic syndrome is a primary cause of renal failure and is characterized by nephrotic range proteinuria that does not respond to conventional steroid therapy. The current work was intended to investigate the possible role of the Phospholipase C epsilon 1 (rs7922612) and collagen4 alpha 3 (rs375290088) single nucleotide polymorphisms as risk factors for developing nephrotic syndrome among Egyptian children. The study was conducted on 100 children with nephrotic syndrome and 100 age- and sex-matched healthy individuals. Geno typing was performed by two methods of polymerase chain reaction for the analysis of PLCE1 (rs7922612) and COL4A3 (rs375290088) variants. We observed a higher percentage of the heterozygous and homozygous variant genotypes of PLCE1 (rs7922612) SNP in NS patients in comparison with the controls (P < 0.001 for both). The frequencies of the PLCE1 (rs7922612) variant showed a statistically significant elevated risk of NS using several genetic models, including the dominant (OR = 9.12), recessive (OR = 2.31), and allelic (OR = 1.62) models (P < 0.001 for each). In addition, the PLCE1 (rs7922612) genotypes and alleles frequencies did not differ significantly between SRNS compared to SSNS cases. Furthermore, there was no significant difference regarding COL4A3 (rs375290088) polymorphism, neither between the NS and control groups nor between SDNS and SRNS. PLCE1 (rs7922612) is considered an independent risk factor for nephrotic syndrome in Egyptian pediatrics.COL4A3 (rs375290088) polymorphism is not correlated to Egyptian NS patients.

Ocular Damage Index, Ocular Pain and Subjective Visual Rating in Patients with Behçet’s Uveitis: A Study of Impact on Health-Related Quality of Life

ABSTRACT Purpose The aim of our study is to assess subjective disease burden parameters (SVR and OP) as well as objective ones (BCVA and ODI) as predictors of HRQoL in Egyptian patients with BD uveitis. Methods Ninety-six patients with BD uveitis were recruited in this cross-sectional study from the Rheumatology Department, Cairo University Hospital. HRQoL was assessed using RAND-36 item health survey 1.0, subjective visual rating (SVR) was measured on a 6-point Likert scale. Ocular pain (OP) was rated on a numeric rating scale. The Ocular Damage Index (ODI) was calculated using the ocular domain of the BD damage index. Linear regression was performed to determine predictors of HRQoL metrics. Results SVR predicted Vitality (β = 0.15, p = 0.004), Emotional Well-being (EW) (β = 0.13, p = 0.005), General Health (β = 0.18, p = 0.012) and Mental Component Summary (β = 0.22, p = 0.002). OP predicted Social Function (β = -3.18 p < 0.001), General Health (β = −1.55, p = 0.004), Physical Component Summary (β = -2.00, p = 0.007) and Mental Component Summary (β = -1.53, p = 0.005). BCVA predicted Physical Function (β = 31.1, p = 0.02) and Emotional Well-being (β = 7.94, p = 0.01). ODI failed to predict any HRQoL metrics. ODI was independent predictor of legal blindness adjusted for uveitis duration and severity. Legally blind patients had worse HRQoL metrics than patients with better vision. Conclusion In BD uveitis patients, subjective disease burden parameters were more informative about HRQoL metrics than objective ones. Longitudinal studies are needed to elucidate the utility of ODI as an outcome measure in BD uveitis. Precis In Behcet’s uveitis patients, health-related quality of life was related to visual outcome, ocular pain, and subjective visual rating. Ocular damage was an independent predictor of legal blindness, adjusted for uveitis duration and severity.

Prevalence and Risk Factors of Cerebral Microbleeds among Egyptian Patients with Acute Ischemic Stroke.

Cerebral microbleeds (CMBs) are markers of underlying hemorrhage-prone cerebral small vessel disease detected on MRI. They are associated with a heightened risk of stroke and cognitive decline. The prevalence of CMBs among Egyptian patients with ischemic stroke is not well studied. Our aim was to detect the prevalence of CMBs and associated risk factors among Egyptian patients with ischemic stroke. A prospective, cross-sectional, single-center study of consecutive patients with ischemic stroke. Patients were recruited between January 2021 and January 2022 at the Assiut University Hospital in the south of Egypt. Patients with known bleeding diathesis were excluded. All participants underwent full neurological assessment, urgent laboratory investigations, and MRI with T2* sequence. The study included 404 patients, 191 (47.3%) of them were females. The mean age of the study population was 61 ± 1 years, and the mean NIHSS on admission was 12 ± 5. The prevalence of CMB was 26.5%, of whom 6.5% were young adults (age ≤45 years). CMBs were detected in 34.6% of patients with stroke caused by large artery atherosclerosis, 28.0% with small vessel disease stroke subtype, 25.2% with stroke of undetermined cause, and in 12.1% with cardioembolic stroke. History of AF, hypertension, dyslipidemia, Fazekas score &gt;2, dual antiplatelet use, combined antiplatelet with anticoagulant treatment, and thrombolytic therapy remained independently associated with CMBs following multivariable regression analyses. The high number of identified CMBs needs to inform subsequent therapeutic management of these patients. We are unable to determine whether the association between CMBs and antithrombotic use is a causal relationship or rather confounded by indication for these treatments in our observational study. To understand more about the underlying cause of this finding, more studies are needed.

A novel MALT1 variant in an Egyptian patient presenting with exfoliative dermatitis: a case-based review.

Inborn errors of the CARD11-BCL10-MALT1 (CBM) signalosome have recently been shown to underlie severe combined immunodeficiency (SCID) and combined immunodeficiency (CID) with variable immunological and clinical phenotypes, and patients usually present with recurrent bacterial, viral, and fungal infections, periodontal disease, enteropathy, dermatitis, and failure to thrive. In the present study, we describe the clinical and immunological characteristics of an Egyptian patient with a mutation in the MALT1 gene. The patient suffered from an itchy exfoliative skin rash and eczematous lesions over his face and flexural surface of the limbs. He also had dental enamel erosion, repeated attacks of diarrhea, and pneumonia. He had elevated serum IgE and normal B- and T-lymphocyte subset counts, but there was an arrest in the B-cell maturation. DOCK8 expression on the lymphocytes by flow cytometry was normal. Next-generation sequencing revealed a novel homozygous variant in the MALT1 gene (c.762dup in exon 5 of 17; p.Ile255TyrfsTer10); this variant is likely pathogenic, thus supporting the genetic diagnosis of immunodeficiency-12 (IMD12). Although the presence of eczema, recurrent sinopulmonary, and staphylococcal infections are suggestive of DOCK8 deficiency, they are also a finding in CARD11 and MALT1 deficiency. Thus, whenever DOCK 8 has been excluded, the molecular diagnosis is mandatory as this could lead to discovering more patients hence better understanding and reporting of the phenotype and natural history of the disease especially since there are very few documented cases. Early diagnosis will also enable the proper patient management by hematopoietic stem cell transplantation (HSCT) prior to the establishment of infections and pulmonary damage leading to a better outcome.