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Shaimaa E Kabil,1 Rania Abdelshafy,1 Ahmed Ismail Abbas Ahmed,1 Alhassan Mostafa Zahran,2 Mahmoud Attalah,2 Yossra Sallam,1 Aisha Ghanem Abd El Lateef3 1E. N. T Department, Faculty of Medicine Cairo, Al-Azhar University, Cairo, Egypt; 2Pediatric Department, Faculty of Medicine Cairo, Al-Azhar University, Cairo, Egypt; 3Psychiatric Department, Faculty of Medicine Cairo, Al-Azhar University, Cairo, EgyptCorrespondence: Shaimaa E Kabil, Email Shaimaa.kabil@azhar.edu.egObjective: Language disorders (LD) in autism spectrum disorders (ASD) are highly variable and has a severe impact on the level of functioning in autistic children. Early diagnosis of these language disorders is essential for early interventions for children at risk. The electrophysiological measurements are considered valuable tools for determining language disabilities in children with ASD. This study aimed to study and compare ABR and MMN in autistic children with language disorders.Methods: This study included a group of typically developing children and a group of children diagnosed with autistic spectrum disorders and language disorders. Both groups were matching according to age and gender. After confirming bilateral normal peripheral hearing sensitivity, ABR was done and both absolute and interpeak wave latencies were correlated. MMN using frequency oddball paradigms were also obtained and correlated.Results: More abnormalities were reported in ABR test results in the form of delayed absolute latencies and prolonged interpeak intervals. Also, we reported prolonged latencies of MMN. Consequently, both ABR and MMN are complementary test in evaluating autistic children with language disorders.Conclusion: Our results support the hypothesis of remarkable dysfunction in basic auditory sound processing that may impact the linguistic development of autistic children.Keywords: Autism spectrum disorders, Language Disorders, Auditory brain stem response, Mismatch negativity

Asmaa M Zahran,1 Omnia El-Badawy,2 Lamiaa M Kamel,3 Amal Rayan,4 Khalid Rezk,5 Mona H Abdel-Rahim2 1Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 2Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 4Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 5Surgical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, EgyptCorrespondence: Amal Rayan Email amal3774rayan@gmail.com; amalrayan@aun.edu.egBackground and Aim: The present study was conducted to evaluate the number of Tregs in triple negative breast cancer (TNBC), in normal breast parenchyma and in the peripheral blood of these patients and controls, in addition to their correlations with the clinico-pathologic features and the outcomes of TNBC.Methods: Thirty adult treatment-naïve women with non-metastatic TNBC were recruited. In addition, 20 ages matched healthy females participated as a control group. Peripheral blood samples were collected from all participants in tubes containing heparin, fresh tumor tissues were also obtained from all patients undergoing surgery, and 20 normal breast tissue samples were obtained from the same patients’ areas adjacent to the safety margins; all these samples were taken for flow cytometric detection of Tregs.Results: The mean percentages of CD4+CD25+highT cells and Tregs were higher in TNBC peripheral blood than healthy controls and in malignant tissue than normal tissue. Moreover, the frequencies of tumor-infiltrating CD4+T cells and Tregs were exceeding those in the peripheral blood of cancer patients. Only tumor-infiltrating Tregs have shown increasing levels with the increase in the tumor size and were significantly higher in patients with local recurrences than those without recurrence. In addition, Tregs showed significant inverse relation with DFS and direct relation with the level of the peripheral Tregs.Conclusion: The findings of the current study support the possibility that TNBC microenvironment conveys specific characteristics on Tregs distinguishing them from those in normal breast tissue or Tregs in peripheral blood, improving the capabilities of tumor-infiltrating Tregs to enhance tumor growth, local recurrence and reduce the DFS.Keywords: triple negative breast cancer, Tregs, disease free survival, recurrences

Helal F Hetta,1,2,* Alaa AA Mohamed,3,* Asmaa M Zahran,4,* Safaa A Mahran,3 Marwa MY Sayed,5 Mohamed GA Saleh,6 Khaled Abdelazeem,6 Gaber El-Saber Batiha,7 Salim Al-Rejaie,8 Yasir Waheed,9 Khalid Muhammad,10 Manal M Hassanien3 1Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 2Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 3Rheumatology and Rehabilitation Department, Faculty of Medicine, Assiut University, Assiut, Egypt; 4Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 5Department of Cardiology, Faculty of Medicine, Assiut University, Assiut, Egypt; 6Department of Ophthalmology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; 7Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicines, Damanhour University, Damanhur, 22511, Egypt; 8Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 9Foundation University Medical College, Foundation University Islamabad, Islamabad, 44000, Pakistan; 10Department of Biology, College of Science, United Arab Emirates University, Al Ain, 15551, United Arab Emirates*These authors contributed equally to this workCorrespondence: Helal F HettaDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, 71515, EgyptEmail helalhetta@aun.edu.egBackground and Aim: The data about the role of regulatory B cells (Breg) in Behcet Disease (BD) are scarce. We aimed to evaluate the frequency of total B lymphocytes and Breg cells in different BD phenotypes and therapies attempting to unravel their function.Methods: This cross-sectional study included 35 BD patients and 39 healthy controls (HCs). The demographic data of the study subjects were collected including age and gender. Current medications including disease-modifying anti-rheumatic drugs (DMARDs) were recorded. All patients underwent testing for baseline laboratory investigations including full blood count, liver and kidney function tests, erythrocyte sedimentation rate (ESR) by Westergren blot and C-reactive protein (CRP). Measurement of the total B lymphocytes and their subtypes B regulatory lymphocytes by flow cytometric assay. Assessment of BD activity was done using the revised Behçet’s Disease Current Activity Form (BDCAF) 2006 and Behçet’s Syndrome Activity Score (BSAS) 1111111111. All participants were assessed for the presence of erectile dysfunction using the International Index of Erectile Function (IIEF-5 score), and for depression using the Beck Depression Inventory.Results: A dramatic drop in the number of B cells, total and regulatory, was observed in the patients compared to the HCs. Regulatory cells (Bregs) tend to be upregulated with genital ulcers or vascular disease. Bregs but not B lymphocytes were associated with BSAS and ESR. Neither the total B lymphocytes nor the Bregs correlated with CRP or the sexual function or depression scores. Of all the used medications, low-dose aspirin was seen with markedly high Bregs proportions.Conclusion: This study supports the role of B cells in BD pathogenesis and strongly suggests a possible role for Bregs in the resolution of different BD manifestations.Keywords: Behcet’s disease, B lymphocytes, Breg

Khaled Elzorkany,1,2 Mahmoud Abd-Elaziz Kora,1 Aliaa Sabry Abdel Wahed,3 Hassan El-Sayed Zaghla,3 Ahmed Mohamed Zahran,1 Yassein Salah Yassein,1 Asmaa Zaki El Naggar,4 Abdallah Essa,5 Abdelnaser Abdelaty Gadallah1 1Internal Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, Egypt; 2Internal Medicine Department, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia; 3Hepatology and Gastroenterology Department, National Liver Institute, Menoufia University, Shibin El- Kom, Egypt; 4Menshawy Hospital, Tanta, Egypt; 5Tropical Medicine Department, Faculty of Medicine, Menoufia University, Shibin El-Kom, EgyptCorrespondence: Khaled ElzorkanyInternal Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, EgyptTel 00201002827630Email khaledelzorkany@med.menofia.edu.egPurpose: Direct acting antiviral agents (DAAs) have greatly improved the clearance of hepatitis C virus (HCV) infection. The effect of DAAs on renal function in post-liver transplant HCV-positive patients remains questionable, especially considering the possibility of drug interactions between immunosuppressants and DAAs.Patients and methods: A retrospective observational study included 84 post-liver transplant patients with HCV infection. Patients were divided into two groups: group I received sofosbuvir plus ribavirin for 24 weeks, group II received sofosbuvir plus daclatasvir for 12 weeks. Laboratory data and eGFR were determined before, at the end, and 6 months after completion of treatment.Results: The treatment was well tolerated with 100% sustained virologic response (SVR 12). There was no statistically significant difference between the two groups regarding clinical and laboratory data before treatment. Mean eGFR significantly reduced from 87.36 mL/min to 76.16 mL/min in group I (P=0.001). However, within 6 months after treatment, mean eGFR recovered to 81.51 mL/min, which was not significant when compared to baseline eGFR (P=0.09). Mean eGFR in group II showed non-significant change. There were no significant changes in immunosuppressive drug levels and eGFR in either group of patients, who received either ciclosporin or tacrolimus before and at the end of treatment.Conclusion: DDAs in post-liver transplant patients with HCV infection were well tolerated and associated with stable renal function. Moreover, sofosbuvir plus daclatasvir regimen showed relatively better renal safety compared to sofosbuvir plus ribavirin.Keywords: renal function, hepatic transplantation, direct acting antiviral agents, hepatitis C treatment

Asmaa M Zahran,1 Sohair K Sayed,2 Heba A Abd El Hafeez,2 Walaa A Khalifa,3 Nahed A Mohamed,4 Helal F Hetta5,6 1Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt; 2Department of Clinical Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt; 3Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt; 4Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Assiut, Egypt; 5Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 6Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA Background: Circulating microparticles (MPs) contribute to the pathogenesis of atherothrombotic disorders and are raised in cardiovascular diseases. Herein, we aimed to investigate the effect of moderate metabolic abnormalities in an early stage of metabolic syndrome (MetS) on the level of MP subpopulations and to study relationships between MP subpopulations and both oxidative stress and coagulation markers. Methods: Flow cytometry used to evaluate circulating MPs subpopulations in 40 patients with an early stage MetS and 30 healthy controls. ELISA was used to quantify plasminogen activator inhibitor type 1/tissue plasminogen activator (PAI-1/TPA) while plasma glutathione peroxidase (GPx) activity was measured spectrophotometrically. Results: Total MPs were significantly elevated in MetS (P

Noura H Abd Ellah,1,2 Esraa A Ahmed,3 Rasha B Abd-ellatief,3 Marwa F Ali,4 Asmaa M Zahran,5 Helal F Hetta6,7 1Division of Pharmaceutical Sciences, James L Winkle College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267, USA; 2Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt; 3Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt; 4Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71515, Egypt; 5Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt; 6Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0595, USA; 7Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71526, Egypt Background: The inflammatory basis of diabetes mellitus directed the researchers’ attention to the immune system for better management and prevention of complications. Metoclopramide (MCA; the only US Food and Drug Administration-approved for gastroparesis) has the ability to restore immune function through increasing prolactin secretion. This study aimed to test the effect of BSA/MCA nanoparticles (NPs) on modulating immune response. Methods: BSA/MCA NPs were fabricated by desolvation and evaluated in vitro via measuring loading efficiency, particle size, and surface charge. The selected formula was further evaluated via differential scanning calorimetry and release behavior. Then, NPs were injected into rats (25 mg MCA/kg/week) for 3 weeks to be evaluated histopathologically and immunologically via measuring proinflammatory cytokines, such as IL1β, IL6, and TNFα, in addition to measuring regulatory T-cell frequency. Results: MCA was successfully loaded on BSA, achieving high encapsulation efficiency reaching 63±2%, particles size of 120–130 nm with good polydispersity, and a negative surface charge indicating that entire positively charged drug was encapsulated inside NPs. Differential scanning calorimetry thermography of selected NPs showed an obvious interaction between components and cross-linking of BSA molecules using glutaraldehyde, resulting in sustained release of MCA (around 50% within 3 days). MCA NPs significantly restored the immune response via decreasing proinflammatory cytokines and increasing regulatory T-cell frequency when compared to control and free MCA (drug not loaded in NPs)-treated groups. Histopathological examination of this MCA NPs-treated group did not show the characteristic lesions of diabetes, and apoptosis nearly disappeared. Conclusion: BSA/MCA NPs could be considered a new modality for treatment of gastroparesis, in addition to management of diabetes itself and preventing its complications via an MCA-immunomodulatory effect. Keywords: metoclopramide, bovine serum albumin, diabetes, immunity, nanoparticles, gastroparesis

Asmaa M Zahran,1 Amal Rayan,2 Hussein Fakhry,3 Alia M Attia,4 Ahmed M Ashmawy,5 Ahmed Soliman,6 Azza Elkady,7 Helal F Hetta8,9 1Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt; 2Department of Clinical Oncology, Assiut University Hospital, Assiut University, Assiut, Egypt; 3Department of Surgical Oncology, South Egypt Cancer Institute, Assiut, Egypt; 4Department of Radiation Oncology, South Egypt Cancer Institute, Assiut, Egypt; 5Department of Internal Medicine, Assiut University Hospital, Assiut, Egypt; 6Department of General Surgery, Faculty of Medicine, Assiut University, Assiut, Egypt; 7Sohag University Medical Administration, Sohag, Egypt; 8Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt; 9Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA Background and aim: Colorectal cancer is one of the most common malignant tumors worldwide. As CD133 and CD44 are notable markers of cancer stem cells (CSCs) identity, it is thought to be a predictive indicator for colorectal cancer. The aim of this study was to investigate the cell cycle state of CD133+ CD44+ and CD133− CD44−cells, isolated from primary human colorectal tumors, and to assess the clinical impact of CD133+ CD44+ CSCs on patients’ outcome regarding disease-free survival (DFS) and overall survival (OS).Materials and methods: Tissue samples were collected from 50 primary colorectal cancer patients. Flow cytometric analysis was performed to isolate tissue CD133+ CD44+ CSCs and CD133− CD44− tumor cells from primary colorectal cancer tissue to compare the cell cycle of both types of cells. Also circulating CSCs were assessed by flow cytometry.Results: Higher percentage of tissue CD133+ CD44+ CSCs isolated from colorectal cancer patients was found in G0/G1 phase. However, tissue CD133− CD44− tumor cells were predominantly found in the S phase; there were significant negative correlations between tissue CD133+ CD44+ CSCs and DFS and OS (r=−0.470, P

Data demonstrated the role of natural killer (NK) cells in systemic lupus erythematosus (SLE). We aimed to determine the immunophenotype and frequency of NK cells and their subsets, CXCR3, CD161 expression in blood and renal tissue of SLE patients with and without lupus nephritis and their relationship with disease activity. The study included 31 SLE patients and 11 controls. Study participants underwent full history and thorough clinical examination. SLE patients underwent routine laboratory investigations. Renal tissue biopsies were taken from patients with lupus nephritis. The frequency of NK cell subsets in blood of patients and controls and renal tissue from patients was performed by flow cytometry. An increase in circulatory CD56bright NK cells and its CD56bright CD16dim subtype was associated with the severity of systemic manifestations in SLE patients. Total CD56bright NK cells and its CD56bright CD16bright subtypes in renal tissues were related to renal damage. We detected decreased CD161 expression on NK cells related to renal damage and severity of systemic manifestations in SLE patients. Decreased expression of CXCR3 on NK cell surface in renal tissues causes misdirected trafficking of NK cells that seems to reduce the severity of lupus nephritis. In conclusion, our results paved the way to understanding the role of NK cells in the pathogenesis of SLE which may represent a future target for immune therapy of SLE. NK and CD56dim subset were decreased in the blood and increased in renal tissue of SLE patients, while the CD56bright subset was increased in blood and decreased in renal tissue reflecting their effects on renal damage and severity of manifestations in SLE., (Copyright© by the Egyptian Association of Immunologists.)

Chronic renal failure (CRF) is an incurable disease with unique challenges. Anemia is a frequent complication affecting dialysis patients. Erythropoietin (EPO) is used to treat anemia, but a poor response may result. We investigated genetic polymorphisms of store-operated calcium channel (SOC) signaling, an important erythropoietin-activated pathway that may induce EPO resistance in patients with renal failure. A total of 108 end stage renal disease (ESRD) patients were selected for this study. Patients were divided into two groups according to their erythropoietin resistance index (ERI): 39 patients with an ERI>10 and 69 patients with an ERI<10. We selected four tagging single nucleotide polymorphisms (tSNPs) in STIM1 and five in ORAI1 in our study. A polymerase chain reaction was performed, and genotyping against EPO resistance was correlated. Patients with the AG genotype of rs1561876 in STIM1, the TC genotype of rs6486795 in ORAI1, and the TG or GG genotypes of rs12320939 in ORAI1 were associated with an increased risk of erythropoietin resistance. Overall, we reported a moderately significant relationship between genetic polymorphisms of STIM1 and EPO resistance. We also reported a highly significant relationship between genetic polymorphisms of ORAI1 and EPO resistance. The (A-A-G) haplotype of STIM1 and the (G-T-G-T-A, G-C-G-C-G, or G-T-T-C-G) haplotypes of ORAI1 were significantly associated with EPO resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The current study was conducted to explore the impact of macrophages and programmed cell death protein 1 (PD-1) expression on tumor-infiltrating lymphocytes (TILs) on treatment outcomes and to define the interaction between these factors and the clinicopathologic features of advanced cholangiocarcinoma (CCA) patients., Methods: Twenty-five patients with metastatic CCA were recruited for the current study from El-Rajhi Hospital and the Clinical Oncology Department of Assiut University. Additionally, 19 healthy controls were included. Before the flow cytometric detection of immune cells, the diagnosis and staging of CCA were performed based on surgical intervention, imaging, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) determinations. This was followed by flow cytometric detection of CD4 + , CD8 + , CD4 + PD-1 + , CD8 + PD-1 + , and CD11b + CD68 + macrophages in the peripheral blood of both patients and controls., Results: The current results revealed higher levels of CD4 + , CD8 + , and CD11b + CD68 + macrophages in controls compared to patients. At the same time, PD-1 expression was significantly higher in patients compared to controls. CD4 + was correlated with improved progression-free survival (PFS), while CD8 + PD-1 was associated with shorter PFS. In general, CD4 + and CD8 + levels progressively increased with improved response to treatments, differentiation, single organ site metastasis, and surgical interventions. On the contrary, PD-1 expression and macrophages progressively increased with worsening response, dedifferentiation, multiple organ sites, and surgical interventions. The median PFS was 12 months, and the mean ± standard error (SE) was 13.1 ± 1.3., Conclusions: CCA has a desmoplastic microenvironment with complex immunologic topography and tumor-reactive stroma. The immune landscape of the peripheral blood mononuclear cells (PBMCs) in CCA patients before treatment could reflect the state of systemic immune function and response to treatments. Our results revealed that T-lymphocytes correlated with better prognosis while macrophages and PD-1 + expression were associated with poor outcomes., Competing Interests: All authors declared that they had no conflict of interest., (Copyright 2024, Zahran et al.)

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by an isolated decrease in platelets below 100 × 10 9 /l after the exclusion of other conditions associated with thrombocytopenia. We investigated the role of different memory T-cell subsets, including T stem cell memory (T SCM ), in children diagnosed with primary ITP and its association with therapeutic duration. This case-control study included 39 pediatric patients with acute ITP admitted to the Children's Hospital at Assiut University. Using a FACSCanto flow cytometer, CD8 + and CD4 + T-lymphocytes were gated. Five different subsets were characterized in each of these cells according to CD45RO and CD45RA expression. Afterward, gating was performed based on CCR7, CD95, and CD27. Examination of the CD8 + T cells subpopulation showed that Central memory T (T CM ) and CD8 + Naïve T (T N ) cells were significantly lower in ITP patients than in healthy children (p < 0.0001) and (p = 0.01), respectively. In addition, CD8 + T EMRA was significantly higher in ITP children than in controls (p = 0.001). CD4 + T CM cells were significantly lower in the ITP patient group (p = 0.04). However, CD4 + T EM was significantly higher in patients than controls (p = 0.04). Our research found that ITP patients had an imbalance in the ratio of CD4 + to CD8 + T cells in the peripheral blood and that T CM cells may be involved in the pathogenetic mechanism of ITP. T CMs could help in prediction of patients with higher risk of developing ITP., (© 2024. The Author(s).)

Pregnancy results in an increase in immune cells, especially monocytes, which enhances the innate immune system. The increase of inflammatory cytokines in pregnant women's amniotic fluid, can cause uterine contraction, is linked to preterm labor. These inflammatory responses are controlled by Toll-like receptors (TLRs), which are largely expressed on neutrophils and monocytes. This study aimed to determine the role of neutrophils and monocyte subsets, as well as their expression of TLR-2 and TLR-4 in women with preterm and full-term delivery. The study involved a total of 74 women, comprising of 29 preterm labor, 25 full-term labor, and 20 non-pregnant women. The distribution of three monocyte subsets, namely (CD14++CD16-), (CD14+CD16+), and (CD14-/dim CD16++) was measured. Also, the expression of TLR2 and TLR4 in monocytes and neutrophils was analyzed using flow cytometry. Non-classical monocytes and intermediate monocytes were significantly higher in the preterm group than the control and full-term groups (p=0.041, p=0.043, and p=0.004, p= 0.049, respectively). Women in the preterm group showed significantly TLR2 expression on nonclassical monocytes compared to the control and full-term groups (p=0.002, and p=0.010, respectively). Also, preterm group expression of TLR4 was significantly higher in classical monocytes and nonclassical monocytes in comparison to the control group (p=0.019, and p≤0.0001, respectively). Besides, TLR4 expression was significantly up regulated in the preterm group compared to full-term in non-classical monocyte subset (p < 0.0001). Moreover, the expression of TLR-4 in neutrophils from the preterm group was statistically higher than expression from the full-term labor and control groups (p < .0001 for both). Such findings highlight the important role of monocyte subsets and neutrophils in activating the innate immune system and initiating strong pro-inflammatory responses that induce preterm labor. Additionally, TLR4 and TLR2 expressions on non-classical monocytes may be used as a marker to assess the probability of preterm labor., (Copyright© by the Egyptian Association of Immunologists.)

Ethnopharmacological Relevance: Although burn wound management in medical practice has improved, the challenge still exists and demands multidisciplinary participation. Wheat has been extensively used as a remedy of different skin conditions especially burns in almost all parts of Italy. However, the mechanism is still unclear., Aim of the Study: To examine the effects of different wheat bran extracts on the healing of burn wound estimated grossly, histopathologically, and immunologically., Materials and Methods: Wistar male rats were divided into 5 groups; (control) saline treated group, Mebo (Moist Exposed Burn Ointment), cold-water extract, hot-water extract and methanolic extract groups. After the burn, four groups from the experimental groups were treated with Mebo, cold-water extract, hot-water extract and methanolic extract, respectively, but the negative-control group was treated daily with saline only. The observation was made along days 0, 5, 9, 13, 17 and 21. At the end of the study, rats were sacrificed, and blood samples were collected for biochemical and cytokines estimation in addition to wound samples were collected for histopathological and immunohistochemical studies., Results: The histopathological examination showed that the inflammation was significantly decreased in all extract-treated groups when compared with saline and Mebo-treated groups. Epithelial tissue and granulation tissue formation most significantly appeared in the cold water extract-treated group., Conclusions: Cold water and methanolic extract groups showed the most rapid and effective healing of the burn wound. Particularly the cold-water extract, due to the sufficient concentration of zinc and phenolic components., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression. Our study included 73 hospitalized COVID-19 patients, of which 33 were moderately affected and 40 suffered from severe infection. A flow cytometric analysis was used to analyze the frequency of T-regulatory cells (T-regs), CD39+ T-regs, and CD39+CD4+ T-cells. Plasma concentrations of adenosine, IL-10, and TGF-β were quantified via an ELISA. An RT-qPCR was used to analyze the gene expression of CD73 and adenosine receptors (A1, A2A, A2B, and A3). T-reg cells were higher in COVID-19 patients compared to healthy controls (7.4 ± 0.79 vs. 2.4 ± 0.28; p < 0.0001). Patients also had a higher frequency of the CD39+ T-reg subset. In addition, patients who suffered from a severe form of the disease had higher CD39+ T-regs compared with moderately infected patients. CD39+CD4+ T cells were increased in patients compared to the control group. An analysis of serum adenosine levels showed a marked decrease in their levels in patients, particularly those suffering from severe illness. However, this was paralleled with a marked decline in the expression levels of CD73. IL-10 and TGF-β levels were higher in COVID-19; in addition, their values were also higher in the severe group. In conclusion, there are distinct immunological alterations in CD39+ lymphocyte subsets and a dysregulation in the adenosine signaling pathway in COVID-19 patients which may contribute to immune dysfunction and disease progression. Understanding these immunological alterations in the different immune cell subsets and adenosine signaling provides valuable insights into the pathogenesis of the disease and may contribute to the development of novel therapeutic approaches targeting specific immune mechanisms.

Objective: Data regarding the imbalance in follicular helper T (Tfh) and follicular regulatory T (Tfr) cell responses in patients having chronic rhinosinusitis with nasal polyps (CRSwNP) is so far limited. Thus, we aimed to assess the changes in circulating Tfh and Tfr in CRSwNP patients., Methods: This case-control study included 21 patients having CRSwNP and 20 age and sex-matched healthy blood donors as a control group. Lund-Mackay staging system was used for radiologic scoring of chronic rhinosinusitis. Two milliliters of peripheral blood samples were collected from all participants into EDTA-containing vacutainer tubes to assess the levels of Tfh and Tfr cells using flow cytometry., Results: Patients having CRSwNP did not show significant differences in the percentages of CD4+ T cells and total CD4+CXCR5+ T cells from healthy controls. Meanwhile, levels of both activated circulating Tfh and Tfr showed a marked rise in patients than controls. In addition, a positive correlation was observed between the levels of both activated Tfh and Tfr cells., Conclusion: An imbalance in circulating Tfh/Tfr levels was detected in patients having CRSwNP. A significant rise in the levels of Tfh and Tfr was detected in patients proposing a possible role of this imbalance in disease pathogenesis.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4 + and CD8 + memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8 + T cells and effector memory-expressing CD45RA CD8 + T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4 + T cells, CD8 + T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8 + TSCMs and CD4 + TNs cells, while female patients had a significantly higher percentage of effector CD8 + CD45RA + T cells. Moreover, altered percentages of CD8 + TNs and memory CD8 + CD45RO + T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Background: Secondary iron overload, alloimmunization, and increased risk of infection are common complications in patients with transfusion-dependent thalassemia (TDT). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune response. This research aimed to study the interaction between Tregs and MDSCs in TDT patients and to evaluate the association of these cell types with disease severity., Methods: This case-control study included 26 patients with TDT and 23 healthy, age- and sex-matched controls. All patients were investigated for complete blood count (CBC), serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets., Results: A significant increase was observed in the frequencies of Tregs and MDSCs, particularly monocytic MDSCs (MO-MDSCs), in TDT patients compared with controls. The frequencies of these cells showed a direct association with ferritin level and total leukocyte count and an inverse association with hemoglobin level. Furthermore, a positive correlation was observed between Tregs and each of the total MDSCs and MO-MDSCs., Conclusions: Levels of Tregs and MDSCs increased in TDT and may probably have a role in suppressing the active immune systems of TDT patients., Competing Interests: None to declare., (Copyright 2023, Zahran et al.)

The study included 32 women with PAS and 20 with normally implanted placenta as a control group. Vascular endothelial cell growth factor (VEGF), Soluble FMS Like Tyrosine Kinase (sFLT-1/sVEGFR1), and Endoglin (ENG) were measured in placenta tissue by ELISA. Granzyme B (GrzB) expression in trophoblastic and stromal mesenchymal cells was evaluated by immunohistochemistry. MAIT, NK, and NKT cells were assessed in blood and placenta by flow cytometry. Alterations were observed in levels of MAIT cells, NK cell subsets, and NKT cells in patients compared with controls. Several significant correlations were detected between these cells and GrzB scores, VEGF, ENG, and sFLT-1 levels. This is the first study analysing these cells in PAS patients and correlating their levels with changes in some angiogenic and antiangiogenic factors implicated in trophoblast invasion and with GrzB distribution in trophoblast and stroma. Interrelation between these cells probably plays an important role in pathogenesis of PAS., (© 2023. The Author(s).)

Rationale: GeneXpert MTB/RIF (Mycobacterium tuberculosis/rifampicin) assay is a method for detecting rifampicin resistance (RR-MTB) in suspected samples in less than 2 hours with high sensitivity and specificity yield. This study aimed to use the GeneXpert MTB/RIF assay to determine the frequency of RR-MTB and to study the possible influencing correlates associated with positive results., Subjects and Methods: This is a retrospective cross-sectional study of patients who visited TB clinic in 5 years (2016-2021). According to the data sheet of the patients, all the collected specimens were divided into 2 parts one for diagnosis by Ziehl-Neelsen stain and the other part for GeneXpert analysis. GeneXpert was also used to look for evidence of RR., Results: Out of the 2605 total samples screened, 718 (27.6%) tested positive for MTB on GeneXpert assay; of them 633 (88.4%) were sensitive to Rifampicin, 83 (11.6%) were resistant to Rifampicin and 2 cases were undetermined. Factors contributing to RR-MTB were: smoker/ex-smoker, with 2.5 times more risk (p = 0.013.0, p = 0.001); recurrence cases had a 4-fold increased risk (p < 0.001); patients with very low M. tuberculosis detected on the GeneXpert MTB/RIF test were 8 times more likely to have RR-TB (P = 0.004)., Conclusion: This study disclosed a high-rate MTB in Egyptian probable TB cases. Smoking, recurrence and cases with a very low M. tuberculosis burden noticed on the GeneXpert MTB/RIF test had augmented risk of RR-TB., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2022 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: The function of different populations of the immune system in bladder cancer (BCa) is well established. However, the cohesive role of the immune cell profile of schistosomal BCa at systemic and tissue levels is still lacking, especially in endemic countries. The balance hypothesized between protumorigenic and antitumor molecules determines the prognosis of tumor progression. This study aimed to investigate the frequency of T cell subsets at both blood and tumor tissue, regulatory T(Treg), regulatory B cells (Breg) and proinflammatory cytokines in S. haematobium-related BCa patients in Egypt., Methodology/principal Findings: The frequency of T cell subsets at both blood and tumor tissue, regulatory T(Treg), regulatory B cells (Breg) were studied by flow cytometry and proinflammatory cytokines by ELISA in S. haematobium-related BCa patients in Egypt. The results indicated a significant increase in the activity of T-cell populations, particularly CD3+, CD4+, and regulatory T cells (Tregs), and a decrease in cytotoxic CD8+ T cells in the patient group. An increased proportion of CD19+CD24+CD38+ Bregs and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) was also observed. However, T-cell subpopulations in the tumor microenvironment showed a significant reduction in cancer patients compared to controls. Moreover, positive correlations were observed between the frequencies of Bregs and Tregs, suggesting the promotion of cancer progression besides their relation to the intensity of schistosomal infection., Conclusions/significance: Trapped Schistosoma haematobium eggs in bladder tissue might lead to persistent inflammation that contributes to immunomodulation and promotes tumor progression, as evidenced by the increase in peripheral T helper, Tregs, Bregs and serum tumor-promoting cytokines. Considering the role and integrated functions of specific immune responses in BCa could help future diagnostic and therapeutic implications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mohammed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

There are conflicting data regarding the relationship between coronavirus disease 2019 (COVID-19) severity and Caspase-1 (Casp-1), interleukin-1ß (IL-1β), and IL-18. Our study sought to quantify the levels of IL-18, IL-1ß, and Casp-1 as indicators for inflammasome activation in COVID-19 patients at Assiut University Hospitals and to correlate their levels with parameters of disease severity in COVID-19 patients. Serum levels of Casp-1, IL-1β and IL-18 were measured in 63 COVID-19 patients and 26 normal controls by an enzyme linked immunosorbent assay (ELISA). Also, arterial blood gas analysis and laboratory parameters including hemoglobin, platelets, lymphocyte count, liver function test, kidney function test, C-reactive protein (CRP), D-dimer, ferritin and LDH were estimated. Serum levels of Casp-1, IL-1β and IL-18 were significantly higher in the COVID-19 group as compared to controls (p= 0.04, p=0.001 and p=0.03, respectively). Although the three markers were higher in the severe group, yet only IL-1ß showed a significant difference as compared to the non-severe group (p=0.04). IL-18 had significant positive correlations with CRP and ferritin (p = 0.04 and p = 0.02, respectively). IL-1β was positively correlated with alanine aminotransferase. Casp-1 had significant positive correlations with CRP and lactate dehydrogenase (p=0.045 and p=0.001, respectively). Patients showed weak positive correlations between serum level of Casp-1 and each of IL-1β and IL-18. Also, a strong positive correlation was found between IL-1β and IL-18 (p < 0.0001). In conclusion, inflammasome activation was a hallmark in COVID-19 patients. The markers of activation were positively correlated with many parameters of inflammation, may suggest their important roles in the pathophysiology of the disease and its progression. IL-1β was the only marker to be correlated with disease severity and therefore may be suggested as a potential marker for identifying severe COVID-19 patients., (Copyright© by the Egyptian Association of Immunologists.)

Background: Hydroxyurea (HU) has beneficial effects in the management of sickle cell anemia (SCA), but there is a paucity of data on the effect of HU on immune cells in SCA. Herein we aimed to evaluate the effect of HU on immune profiles of Egyptian children with SCA., Methods: This was a controlled prospective cohort study conducted in 30 children with SCA and 30 healthy age-matched controls. Flow cytometry was used to evaluate lymphocyte profiles, including CD8+ T, CD19+ B, CD3+, CD4+, natural killer (NK), NK T, T helper 1 (Th1), Th2, T cytotoxic (Tc1), and Tc2 cells, prior to and after 1 year of treatment with HU., Results: HU treatment led to significant increases in hemoglobin (Hb), red blood cell, and hematocrit counts and a significant decrease in the percentage of sickle Hb, with subsequent improvement in SCA complications. Compared with baseline values, CD3+, CD4+, Th1, and CD8+ T cells were significantly increased, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios., Conclusions: HU has the beneficial effect of restoring the abnormally elevated immune parameters in children with SCA., Impact: Hydroxyurea treatment restores the abnormal immune parameters in children with sickle cell anemia. HU treatment led to significantly increased CD3+, CD4+, Th1, and CD8+ T cells, while NK, Th2, and Tc2 cells were significantly decreased, with a resulting increase in the Th1/Th2 and Tc1/Tc2 ratios. Our study showed the impact of HU therapy on immune parameters in children with SCA., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

We aimed to determine the levels of follicular helper T (Tfh) and follicular regulatory T (Tfr) cells in COVID-19 patients and determine whether their levels correlated with disease severity and presence of hyperglycemia. This study was carried out in 34 hospitalized COVID-19 patients and 20 healthy controls. Levels of total circulating Tfh, inducible T-cell costimulator (ICOS)+ activated Tfh, and Tfr cells were assessed in all participants by flow cytometry. Total CD4+CXCR5+ Tfh cells and ICOS+Foxp3-activated Tfh cells increased and ICOS+Foxp3+ Tfr cells decreased in COVID-19 patients, especially in diabetic patients and those with severe disease. Activated ICOS+ Tfh cells were directly correlated with lactate dehydrogenase, D-dimer, ferritin, and respiratory rate and inversely correlated with the partial pressure of carbon dioxide. COVID-19 is associated with marked activation of Tfh cells and a profound drop in Tfr cells, especially in severe and diabetic patients. Future studies on expanded cohorts of patients are needed to clarify the relationship between SARS-CoV-2 and acute-onset diabetes.

Objectives: Detailed characterisation of CD45RA + and CD45RO + T cell subsets in both CD4 + and CD8 + cells in blood and tissue of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is lacking. We aimed to investigate T cell differentiation levels in blood and tissue and correlate this with CT score and white blood cell count., Methods: This case-control study was conducted on 21 patients with CRSwNP and 20 healthy controls. Lund-Mackay score was used for radiologic staging of chronic rhinosinusitis. T cell subsets were characterised in blood and nasal polyp tissue using CD4, CD8, CCR7, CD45RA, CD45RO, CD27, and CD95 monoclonal antibodies., Results: Most variations in T cell subsets were detected in tissue rather than blood. A higher level of CD8 + T CM , CD4 + T SCMs and lower level of CD8 + T EM were detected in the blood of CRSwNP patients vs controls. In CRSwNP patients, substantial decrease of tissue CD8 + T Ns , CD8 + T CMs , CD4 + T Ns, and CD4 + T SCMs with marked increase in the percentages of T EMs and T EMRAs were detected among CD4 + and CD8 + T cells compared with levels in blood., Conclusions: The reduction of T Ns , T SCMs , and T CMs and accumulation of T EMs and T EMRAs subsets that function as effector cells in sinonasal mucosa, especially CD8 + T cells, might indicate the role of immunomodulation of memory/effector T-cells in the pathogenesis of CRSwNP., (Copyright © 2022 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Coronavirus infectious disease 2019 (COVID-19) confirmed cases are characterized by T lymphopenia. Total apoptotic and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expressing cells among CD4+/CD8+ cells were analyzed in 24 COVID-19 patients (16 out-patients and 8 in-patients) and 18 healthy volunteers using flow cytometry to detect their possible role in T lymphopenia. Hospitalized patients did not show significant difference compared to non-hospitalized patients. While the percentage and absolute count of CD4+/CD8+ cells were significantly reduced in COVID-19 cases compared to healthy control (P < .05), the proportion of apoptotic and CTLA-4 expressing CD4+/CD8+ cells were significantly up-regulated in COVID-19 patients (P < .05). In addition, apoptotic and CTLA-4+/CD4+ cells were directly related to dyspnea duration, chest CT score, ferritin, and C-reactive protein and inversely correlated with platelet count in COVID-19 patients. While apoptotic and CTLA-4+/CD8+ cells were directly related to lymphocyte count in COVID-19 patients. The apoptotic and CTLA-4+ cells were directly related to each other in CD4+/CD8+ cells (P < .05). White blood cells (WBCs) (×103/L), eosinophils (ratio and count), lymphocyte ratio, neutrophil ratio, neutrophil/lymphocyte ratio, neutrophil/CD4 ratio, neutrophil/CD8 ratio, CD4+ cells ratio, and CTLA-4+ cells percentage), and CD8+ cells (ratio, count, total apoptotic cell, and CD152 + cells) were all found to be significantly altered in association with COVID-19. Total lymphopenia and depletion of CD4+/CD8+ cells are characterizing COVID-19 patients. Increased apoptosis and CTLA-4 expression in CD4+/CD8+ cells in COVID-19 and their correlations with reduced cell count and severity indicators as CRP and ferritin can be used for diagnosis and follow up of the clinical severity. Our current study proposes promising future diagnostic and therapeutic targets., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: About 7 million people die from various types of cancer every year representing nearly 12.5% of deaths worldwide. This fact raises the demand to develop new, effective anticancer, onco-suppressive, and chemoprotective agents for the future fighting of cancers. Genistein exhibits pleiotropic functions in cancer, metabolism, and inflammation. It functions as an antineoplastic agent through its effect on the cell cycle, apoptotic processes, angiogenesis, invasion, and metastasis., Aim of the Study: The current study aimed to study the genistein onco-suppressive effects during 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters' buccal pouch utilizing flow cytometry analysis (FMA), as a fast-diagnosing tool, in addition to the histopathology., Material and Methods: The buccal mucosa of adult male Syrian hamsters was painted with paraffin oil only (group 1), DMBA mixed in mineral oil (group 2), or orally administrated genistein along with painting DMBA (group 2B). The buccal mucosa was utilized for flow cytometric analysis and histopathological examination., Results: Grossly, DMBA-induced carcinogenesis started at the 9th week. Progressive signs appeared in the following weeks reaching to large ulcerative oral masses and exophytic nodules at the 21st week. Histologically, invasive well-differentiated oral squamous cell carcinoma (OSCC) appeared in the underlying tissues from the 12th week, showing malignant criteria. Genistein had delayed clinicopathological change, which started 6 weeks later, than the DMBA-painted hamsters, as mild epithelial dysplastic changes. This became moderate during the last 6 weeks, without dysplastic changes. Flow cytometry revealed that DMBA led to considerable variation in DNA proliferation activity, aneuploid DNA pattern, in 47.22% of hamsters and significantly raised the S-phase fragment (SPF) values, which drastically reduced after genistein treatment., Conclusion: Taken together, genistein could be employed as an onco-suppressive agent for carcinogenesis. Moreover, FMA could be used as an aiding fast tool for diagnosis of cancer., (© 2022. The Author(s).)

Background: Regulatory T cells (Tregs) are linked to a reduction in alloreactive immune responses, but few studies have investigated the impact of hydroxyurea (HU) therapy on Tregs in sickle cell disease (SCD)., Methods: Our case-controlled study presented here included two groups, the first comprising 60 pediatric SCD patients, 30 of whom did not receive any treatment and 30 who received HU, and the second group consisting of 30 healthy controls. Flow cytometry was used to evaluate the percentage of CD4 + CD25 +high Foxp3 + Tregs present and their phenotypes., Results: The percentage of CD4 + CD25 +high Tregs was significantly increased in untreated SCD patients in comparison to treated SCD patients and controls. Conversely, treated SCD children had a lower percentage of CD4 + CD25 +high Tregs than controls. In addition, a significant increase in the percentage of CD4 + CD25 +high Foxp3 + Tregs was found in untreated SCD patients, compared to in HU-treated patients and controls. The percentage of naive CD45RA + Tregs was significantly decreased in untreated SCD patients when compared to other groups., Conclusions: Among children with SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs by decreasing their frequency, and increasing the proportion of naive CD45RA + Tregs and reducing levels of the most suppressive Tregs: HLA-DR + , CD39 + , and CD69 + ., Impact: Among children with, SCD, HU treatment exhibited significant qualitative and quantitative effects on Tregs. HU treatment in SCD decreases the frequency of Tregs, as well as the levels of the most suppressive Tregs: HLA-DR + , CD39 + , and CD69 + . At the same time, HU increases the proportion of naive CD45RA + Tregs. Our study showed the impact of HU therapy on Tregs in children with SCD., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Cytotoxic (CD8) T-cells and natural killer (NK) cells have a significant immune function role. The ongoing stimulation of immunity and the excessive release of proinflammatory cytokines observed in pediatric patients with Gaucher disease (GD) can affect immune cells. Few studies have looked at the proportion of cytotoxic CD8 T-cells and their subsets in children with GD. A prospective case-control study was performed involving twenty pediatric patients with type 1 GD and twenty healthy age-matched controls. All patients received regular enzyme replacement therapy (ERT) for at least 6 months before the study. Complete blood count and flow cytometric analyses of CD8 T, Tc1, Tc2, NK, and NK T-cells were performed. GD patients showed significantly increased of CD8 T, Tc1 and significantly decreased NK cells frequencies when compared to healthy controls. However, no significant difference in Tc2 and NK T-cells was found between the studied groups. GD patients on regular ERT have increased CD8+ T-cell frequencies, predominantly Tc1, together with a reduction in NK cells than in healthy controls. These crucial immunological changes may contribute to some extent to the pathogenesis and the progression of GD., (© 2022. The Author(s).)

Background and Aim: Growing evidence highlighted the primary role of the immune system in the disease course of triple-negative breast cancer (TNBC). The study aim was to investigate the expression of PD-1 and CD39 on CD4+ and CD8+ cells infiltrating tumor tissue compared to their counterparts in peripheral blood and explore its association with tumor characteristics, disease progression, and prognosis in females with TNBC., Patients and Methods: The study included 30 TNBC patients and 20 healthy controls. Cancer and normal breast tissue and peripheral blood samples were collected for evaluation of the expression of PD-1 and CD39 on CD4+ and CD8+T cells by flow cytometry., Results: A marked reduction in the percentage of CD8+ T lymphocytes and a significant increase in the frequencies of CD4+ T lymphocytes and CD4+ and CD8+ T lymphocytes expressing PD1 and CD39 were evident in tumor tissue in comparison with the normal breast tissue. The DFS was inversely related to the cancer tissue PD1+CD8+ and CD39+CD8+ T lymphocytes. Almost all studied cells were significantly increased in the tumor tissue than in peripheral blood. Positive correlations were detected among peripheral PD1+CD4+T lymphocytes and each of cancer tissue PD1+CD4+, PD1+CD8+and CD39+CD8+T cells, and among peripheral and cancer tissue CD39+CD4+and CD39+CD8+ T cells., Conclusions: The CD39 and PD1 inhibitory pathways are synergistically utilized by TNBC cells to evade host immune response causing poor survival. Hence, combinational immunotherapy blocking these pathways might be a promising treatment strategy in this type of cancer., Competing Interests: the authors have declared that no competing interests exist

Aim: Our study's objectives were to study the clinical and laboratory characteristics that may serve as biomarkers for predicting disease severity, IL-10 levels, and frequencies of different T cell subsets in comorbid COVID-19 patients., Methods: Sixty-two hospitalized COVID-19 patients with comorbidities were assessed clinically and radiologically. Blood samples were collected to assess the T lymphocyte subsets by flow cytometry and IL-10 levels by ELISA., Results: The most common comorbidities observed in COVID-19 patients were diabetes mellitus (DM), hypertension, and malignancies. Common symptoms and signs included fever, cough, dyspnea, fatigue, myalgia, and sore throat. CRP, ferritin, D dimer, LDH, urea, creatinine, and direct bilirubin were significantly increased in patients than controls. Lymphocyte count and CD4 + and CD8 + T-cells were significantly decreased in comorbid COVID-19 patients, and CD25 and CD45RA expression were increased. CD4 + and CD8 + regulatory T cells (Tregs) and IL-10 levels were significantly decreased in patients., Conclusions: Many parameters were found to be predictive of severity in the comorbid patients in our study. Significant reductions in the levels and activation of CD4 + and CD8 + T-cells were found. In addition, CD4 + and CD8 + Tregs were significant decreased in patients, probably pointing to a prominent role of CD8 + Tregs in dampening CD4 + T-cell activation.

Methods: We recruited 40 cases of advanced NSCLC, stages III and IV, aged > 18-<70 years old, and eligible to receive chemotherapy with or without radiotherapy, along with 20 healthy controls of comparable age and sex; after diagnosis and staging of patients, blood samples were collected for flow cytometric detection of Mo-MDSCs., Results: Significant accumulation of Mo-MDSCs in patients compared to their controls ( p < 0.0001). Furthermore, these cells accumulated significantly in stage IV compared to stage III ( p = 0.006) and correlated negatively with overall survival ( r = -0.471, p = 0.002), lymphocyte to monocyte ratio ( r = -0.446, p = 0.004), and mean platelet volume to platelet count ratio (MPV/PC) ( r = -0.464, p = 0.003), patients with Mo-MDSCs < 13% had significantly better survival than those with Mo-MDSCs ≥ 13% ( p = 0.041)., Conclusion: Mo-MDSCs represent one of the key mechanisms in the immunosuppressive tumor microenvironment (TME) to play major roles not only in the carcinogenesis of lung cancer but also in disease progression and prognosis and, in addition, predict the efficacy of immune checkpoint inhibitors; our results provided some support to target Mo-MDSCs and needed to be augmented by further studies., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Asmaa M. Zahran et al.)

Although multiple myeloma (MM) is still considered as an incurable disease by current standards, the development of several combination therapies, and immunotherapy approaches has raised the hope towards transforming MM into an indolent, chronic disease, and possibly achieving a cure. We tried to shed light on the expression of PD1 and different Microparticles (MPs) in MM and their interplay as a mechanism of resistance to standardized treatments, in addition, find their associations with prognostic factors of symptomatic MM. Thirty patients with newly diagnosed and chemotherapy naïve active MM, along with 19 healthy participants of comparable age and sex were recruited, after diagnosis of MM; blood samples were collected from both patients and controls for flow cytometric detection of CD4+, CD8+, CD4+PD1+, and CD8+PD1+T cells, total MPs, CD138+ MPs, and platelet MPs. MM patients had statistically significant higher levels of TMPs, CD138+ MPs compared to their controls, while PMPs exhibited no significant difference between both groups. Statistically significant higher percentages of CD8+, PD1CD8+, PD1CD4+T cells were detected in patients compared to controls, while the latter group had a significantly higher percentage of CD4+T cells than MM patients, patients who did not achieve complete response, had significantly higher percentages of PMPs, CD138+MPs, PD1+CD8+, PD1+CD4+, and CD8+T cells (cutoff values = 61, 10.6, 13.5, 11.3 and 20.1 respectively), (p-values = 0.002, 0.003, 0.017, 0.001 and 0.008 respectively). Microparticles and PD1 expressions were associated with proliferative potential and resistance to Bortezomib-based treatments, our results suggested that they played a crucial role in myeloma progression., (© 2021. The Author(s).)

Background: There are minimal data on the frequencies of monocyte subsets and dendritic cells (DCs) in children with Gaucher disease (GD), as nearly all previous studies have involved adult patients. Consequently, we aimed to describe the changes in these cell subpopulations in children with GD type 1 who were on regular enzyme replacement therapy (ERT)., Methods: This case-control study included 25 children with GD1 and 20 healthy controls. All participants underwent investigations such as complete blood count and flow cytometric assessment of DC and monocyte frequencies and phenotype., Results: We found that GD1 children had significantly reduced percentages of both types of DCs, i.e., plasmacytoid DCs and myeloid DCs, compared to the control group. There was also a significant reduction in absolute monocyte numbers and percentage of classical monocyte. Moreover, the GD1 children had higher frequencies of non-classical and intermediate monocytes than the control group., Conclusions: Our results so far indicate that, when compared to the control group, the GD1 children had significantly reduced total and classical monocyte, with significantly decreased frequencies for both types of DCs. These changes can contribute to immunological abnormalities in pediatric patients with GD1., Impact: Children with Gaucher disease type 1 (GD1) have significantly reduced total and classical monocyte frequencies, with decreasing percentages for both types of dendritic cells. GD1 children had significantly reduced frequencies of myeloid and plasmacytoid dendritic cells as compared to the controls. The GD1 children also had significant changes in monocyte subsets when compared to the controls. Our results show that monocytes and dendritic cells' significant changes could contribute to immunological abnormalities in pediatric patients with GD1., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Interaction between multiple myeloma (MM) cells and proximal monocytes is expected during plasma cell proliferation. However, the role of monocyte subsets in the disease progression is unknown., Objective: This study evaluated circulating monocyte populations in MM patients and their correlation with disease severity., Methods: Peripheral monocytes from 20 patients with MM attending Assiut University Hospital in Assiut, Egypt, between October 2018 and August 2019 were processed using a flow cytometry procedure and stratified using the intensity of expression of CD14 and CD16 into classical (CD16 - CD14 ++ ), intermediate (CD16 + CD14 ++ ), and non-classical (CD16 ++ CD14 + ) subsets. The data were compared with data from 20 healthy control participants with comparable age and sex., Results: In patients with MM, the percentage of classical monocytes was significantly lower (mean ± standard error: 77.24 ± 0.66 vs 83.75 ± 0.5), while those of non-classical (12.44 ± 0.5 vs 8.9 ± 0.34) and intermediate (10.3 ± 0.24 vs 7.4 ± 0.29) monocytes were significantly higher when compared with those of controls (all p < 0.0001). Proportions of non-classical and intermediate monocytes correlated positively with serum levels of plasma cells, M-protein, calcium, creatinine and lactate dehydrogenase, and correlated negatively with the serum albumin level. Proportions of classical monocytes correlated positively with albumin level and negatively correlated with serum levels of M-protein, plasma cells, calcium, creatinine, and lactate dehydrogenase., Conclusion: Circulating monocyte subpopulations are skewed towards non-classical and intermediate monocytes in MM patients, and the intensity of this skewness increases with disease severity., Competing Interests: The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article., (© 2021. The Authors.)

Our study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients' clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children's Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL., (© 2021. The Author(s).)

Background: Viral infections cause alteration in the total number of lymphocytes and their subset distribution. We aimed to study peripheral blood lymphocyte subsets in COVID-19 patients and to correlate these subsets with clinical and laboratory data, which may help in clarifying the pathogenesis to develop novel diagnostic and prognostic biomarkers for COVID-19., Methods: Twenty-six reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 patients were subjected to medical history-taking and a thorough clinical examination. Laboratory tests included complete blood count, D dimer, ferritin, and C-reactive protein (CRP). Chest CT was used to diagnose COVID-19 pneumonia. Lymphocyte subsets were compared with those in 20 healthy controls using flow cytometry., Results: Leucopenia, relative neutrophilia, lymphopenia, eosinopenia together with marked elevation in neutrophil/lymphocyte ratio were observed in our COVID-19 patients. A marked reduction was observed in T cells, including both CD4 and CD8 cells, natural killer (NK), and natural killer T cells (NKT). Double-positive T (DPT) cells, double-negative T (DNT) cells, and B cells were elevated in the patients relative to the other lymphocyte subsets., Conclusion: Immune-inflammatory parameters are of utmost importance in understanding the pathogenesis and in the provisional diagnosis of COVID-19. Yet, adequate care must be taken during their interpretation because of the vast discrepancies observed between studies even in the same locality. Further studies are needed to clarify the role of B cells, DPT, and DNT cells in the pathogenesis and control of COVID-19., (©Copyright: the Author(s).)

Objective: This study was conducted to investigate the relationship of semen parameters in samples used for intracytoplasmic sperm injection (ICSI) with fertilization and pregnancy rates in infertile couples., Methods: In this prospective study of Infertile couples with male factor infertility that had undergone ICSI, fractions of the same semen samples obtained for microinjection (to ensure the best predictability) were evaluated to determine the semen parameters and sperm DNA fragmentation index (DFI) on the day of oocyte recovery., Results: In total, 120 couples completed the study and were subdivided into fertilized (n=87) and non-fertilized couples (n=33). The fertilized couples were further classified into pregnant (n=48) and non-pregnant (n=39) couples. Compared to non-fertilized and non-pregnant couples, fertilized and pregnant couples showed statistically significantly higher sperm viability and percentage of normal sperm morphology, as well as significantly lower sperm DFI values. A receiver operating characteristic curve analysis of data from the 120 ICSI cycles showed that sperm viability, normal sperm morphology percentages, and sperm DFI were significant prognostic indicators of fertilization at cutoff values of 40%, 7%, and 46%, respectively. A sperm DFI of 46% showed sensitivity and specificity of 95% and 90%, respectively, for predicting fertilization, and no clinical pregnancies occurred in couples with a sperm DFI above 46%., Conclusion: Semen parameters from the ICSI day sample, especially sperm viability, normal morphology, and DFI, had an impact on fertilization and pregnancy outcomes in ICSI cycles.

Background and Aim: Solid tumors, including pediatric malignancies, depend on angiogenesis for tumor growth, invasion, and metastases. We aimed to evaluate the prognostic impact of circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) on treatment response and survival of pediatric patients with solid tumors., Methods: A prospective study included 70 patients with different pediatric solid tumors treated with different types of chemotherapy and 20 age and sex-matched healthy children as controls. Blood samples collected at diagnosis then on day 7 and day 21 after chemotherapy. CECs and EPCs were evaluated using flow cytometry., Results: The mean levels of CECs and EPCs of patients at diagnosis were significantly higher than controls (85.29 ± 24.78 and 26.1 ± 9.11 versus 20.08 ± 6.65; and EPCs; 2.78 ± 1.48, respectively; P < 0.001 for both). The highest levels of CECs were observed in patients with rhabdomyosarcoma (RMS). An overall increase was reported in CECs, and after the first cycle of chemotherapy, that was significantly correlated to treatment response and overall survival., Conclusion: Pediatric patients with solid tumors have elevated levels of CECs and EPCs with more elevation after chemotherapy. The magnitude of increase of CECs occurred on day 7 after chemotherapy may be considered as an early predictor of response to therapy and outcome in pediatric patients with solid tumors.

Background and Aim: Lung cancer is the number one cause of cancer-related deaths. Dendritic cells (DCs) are heterogeneous components of innate immunity that play a crucial role in the anti-tumor T cell immunity and may represent a promising approach for tumor immunotherapy. In this study, we aimed to evaluate the frequency of the two major subsets of DCs; plasmacytoid dendritic cells (pDCs) and monocytic dendritic cells (mDCs) in non-small cell lung cancer (NCSLC) and correlating them with different clinicopathologic features and survival outcomes., Patients and Methods: This study was a case-controlled one, included 50 patients with denovo pathologically confirmed NSCLC and 20 healthy controls of comparable age and gender. After diagnosis and staging of patients, the frequency of DCs was evaluated using flow cytometry., Results: We unveiled significantly reduced levels of pDCs (P = 0.024), and mDCs (P = 0.013) in NSCLC patients compared to controls. Furthermore, there was a significant accumulation of pDCs in non-metastatic patients compared to metastatic ones (P < 0.0001), while there was no significant (P = 0.6) differences in mDCs, and mDCs/pDCs ratio (P = 0.9). There was a Significant negative correlation (r = - 0.3, P = 0.04) between OS and mDCs. On the other hand, there was a significantly higher OS with pDCs ≥ 0.82 compared to patients with pDCs < 0.82, log rank Ch 2  = 12.128, P < 0.0001., Conclusion: Despite the controversy about the prognostic role of pDCs not only in NSCLC but also in other solid tumors, our study sheds light on the possible prognostic impact of pDCs and mDCs on treatment outcomes of NSCLC patients.

Background and Aim: The study aimed to determine whether the MPs levels and platelet activation are affected by the COVID-19 infection in both malignant and non-malignant patients compared to healthy individuals and define their contribution to the COVID-19 associated coagulopathy and the relation of these MPs to other hematologic parameters., Patients and Methods: We recruited 23 malignant patients with reverse transcription polymerase chain reaction (RT-PCR) positive COVID-19, also, 19 COVID-19 non-malignant patients, and 20 healthy volunteers were also enrolled for comparison. Blood samples were collected from patients and healthy donors into 5 mL vacutainer tube containing 3.5% buffered sodium citrate solution for measurement of total microparticles (TMPs), platelet microparticles (PMPs), endothelial microparticles (EMPs), CD62 activated platelets, and CD41 platelet marker., Results: COVID-19 malignant patients had significantly lower hemoglobin and platelets compared to COVID non-malignant ones, while they had significantly higher C-reactive protein, LDH, AST, Albunim, creatinine, and prognostic index (PI) compared to COVID-19 non-malignant patients. significant accumulations of TMPs, PMPs, EMPs, and activated platelets in COVID-19 affected patients compared to healthy controls. TMPs, and EMPs were significantly accumulated in COVID-19 malignant compared to COVID-19 non-malignant patients with no significant difference in PMPs between both., Conclusion: Circulating MPs and activated platelets may be promising novel prognostic biomarkers capable of identifying potentially severe COVID-19 patients who require immediate care especially in cancer patients., Competing Interests: The authors have declared that no competing interests exist.

Background : Dysfunction of the peripheral blood monocytes in the form of changes in their proportion, cytokines or pattern-recognition receptors (PRR) expressions may be involved in the pathogenesis of type 1 diabetes mellitus (T1DM). Our aim is to analyze the three monocyte subsets; classical, non-classical and intermediate monocytes and their expression of Toll-like receptors 2 (TLR-2) and 4 (TLR-4) in T1DM patients. Methods : The peripheral blood monocytes of 20 T1DM patients were analyzed by Flow cytometry to measure their count and TLR-2 and TLR-4 expression. Results : T1DM patients had more non-classical and intermediate monocytes, whereas classical monocytes were comparable between patients and control (20 healthy volunteers). Classical, non-classical and intermediate monocytes had no significant correlations with hemoglobin (Hb) A1C in controls, while all subsets showed positive correlations with HbA1C in T1DM. TLR-2 and TLR-4 expression were significantly increased in classical monocytes in patients, especially those with diabetic ketoacidosis (DKA), and both of them showed positive correlations with the duration of T1DM. The expression of TLR-2 inside non-classical monocytes showed a negative correlation with LDL cholesterol and TLR-4/TLR-2 ratio showed positive correlations with the duration of T1DM and negative correlations with total cholesterol. The expression of TLR-2 inside intermediate monocytes showed positive correlations with the duration of T1DM and TLR-4/TLR-2 ratio showed negative correlations with the duration of T1DM Conclusions: The observed changes in both proportions and TLR-2 and TLR-4 expression of monocyte subsets can raise the possible role in the pathogenesis of early stages of T1DM and DKA. Abbreviations APC: allophycocyanin; CBC: complete blood picture; DKA: diabetic acidosis; DM: diabetes mellitus; FITC: fluorescein isothiocyanate; FSC: forward scatter; Hb: haemoglobin; MFI: mean channel fluorescence intensity; PE: phycoerythrin; PRR: pattern-recognition receptors; SPSS: statistical package for the social sciences; SSC: side scatter; T1DM: Type1DM; TLRs: toll-like receptors.

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.

Regulatory T cells (Tregs) play a fundamental role in maintaining immune homeostasis to balance between the tissue-damaging and protective effects of the immune response. There are strong evidences that Treg cells and their cytokines may play an important role in the induction of tolerance in the liver and progression of HCV infection. Herein, we investigated the frequency of Treg cells and interleukin 35 (IL-35) level in blood and their potential relationship to the various chronic hepatitis C (CHC) complications and outcomes. A total of 36 HCV infected patients subdivided into, CHC complicated with cirrhosis (HCV LC; n = 18), CHC complicated with hepatocellular carcinoma (HCV- HCC; n=18) and apparently healthy control group (n=18) were enrolled in this study. Treg cells percentages were determined by flow cytometric analysis and ELISA was used to measure IL35 serum levels. A significant increase in the frequency of peripheral Tregs and serum IL35 level was found in HCV HCC, and HCV LC groups compared with the control group. The frequency of peripheral Tregs and plasma (IL-35) levels were significantly positively correlated with viral load along with disease progression. We conclude that the higher percentage of Tregs and IL35 level in peripheral blood of HCV HCC and HCV LC groups compared to the control group may suggest their contribution to viral persistence and progression of HCV infection., (Copyright© by the Egyptian Association of Immunologists.)

Type II diabetes (T2D) may worsen the course of hepatitis C virus infection with a greater risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In chronic viral infections, the deranged B cell subset signifies uncontrolled disease. The study aimed to verify the relation between B cell subsets' distribution and liver disease progression in chronic hepatitis C (CHC) patients with T2D. A total of 67 CHC patients were divided into two groups; 33 non-diabetic and 34 with T2D. Each group was subdivided into CHC-without LC or HCC (N-CHC), CHC-with LC (CHC-LC), and CHC-with HCC (CHC-HCC). Twenty-seven healthy individuals also participated as controls. Flow cytometry was used to analyze CD19 + B cell subsets based on the expression of CD24 and CD38. CD19 + CD24 hi CD38 hi Immature/transitional B cells elevated in diabetic than non-diabetic patients. In diabetic patients, while CD19 + CD24 + CD38 - primarily memory B cells were higher in CHC-N and CHC-HCC groups than LC with a good predictive accuracy of LC, the opposite was observed for CD19 + CD24 - CD38 - new memory B cells. Only in diabetic patients, the CD19 + CD24 int CD38 int naïve mature B cells were high in CHC-HCC patients with good prognostic accuracy of HCC. Merely in diabetic patients, several correlations were observed between B cell subsets and liver function. Immature/transitional B cells increase remarkably in diabetic CHCpatients and might have a role in liver disease progression. Memory and Naïve B cells are good potential predictors of LC and HCCin diabetic CHCpatients, respectively. Further studies are needed to investigate the role of the CD19 + CD24 - CD38 - new memory B cells in disease progression in CHC patients.

Prediction of acute kidney injury (AKI) in critically ill patients allows prompt intervention that improves outcome. We aimed for external validation of two AKI prediction scores that can be bedside calculated. A prospective observational study included patients admitted to medical and surgical critical care units. Performance of two AKI prediction scores, Malhotra score and acute kidney injury prediction score (APS), was assessed for their ability to predict AKI. The best cutoff point for each score was determined by Youden index. Area under the receiving operation characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were used to assess performance of each score. Univariate and multivariate regression analyses were done to detect the predictability of AKI. Goodness-of-fit and kappa Cohen agreement tests were done to show whether the expected score results fit well and agree with the observed results. AKI prevalence was 37.6%. The best cutoff values were 5 and 4 for Malhotra score and APS, respectively. Area under the curve for Malhotra 5 was 0.712 and for APS 4 was 0.652 with nearly similar sensitivity and specificity. Regression analysis demonstrated that Malhotra 5 was the independent predictor of AKI. Goodness-of-fit test showed significant results denoting lack of fit between the scores and the actual results. Kappa test showed moderate agreement for Malhotra 5 and fair agreement for APS 4. Both scores showed moderate performance for AKI prediction. Malhotra 5 showed better performance compared to APS 4. Multicenter international study is warranted to develop a universal model that can predict AKI in critically ill patients.