Revisiting double-negative T cells in autoimmune lymphoproliferative immunodeficiencies: a case series.

BACKGROUND: Elevated level of double-negative T (DNT) cells is a historical hallmark of autoimmune lymphoproliferative syndrome (ALPS) diagnosis. However, the peripheral blood level of DNT cells might also be compromised in autoimmune lymphoproliferative immunodeficiencies (ALPID) other than ALPS, inattention to which would increase the delay in diagnosis of the underlying genetic defect and hinder disease-specific treatment. MATERIALS AND METHODS: This cross-sectional study recruited patients suffering from ALPID (exclusion of ALPS) with established genetic diagnosis. Following thorough history taking, immunophenotyping for lymphocyte subsets was performed using BD FACS CaliburTM flowcytometry. RESULTS: Fifteen non-ALPS ALPID patients (60% male and 40% female) at a median (interquartile range: IQR) age of 14.0 (7.6-21.8) years were enrolled. Parental consanguinity and family history of immunodeficiency were present in 8 (53.3%) patients. The median (IQR) age at first presentation, clinical and molecular diagnosis were 18 (4-36) months, 8.0 (4.0-17.0) years, and 9.5 (5.0-20.9) years, respectively. Molecular defects were observed in these genes: LRBA (3, 20%), CTLA-4 (2, 13.3%), BACH2 (2, 13.3%), AIRE (2, 13.3%), and FOXP3, IL2Rß, DEF6, RASGRP1, PIK3CD, and PIK3R1 each in one patient (6.7%). The most common manifestations were infections (14, 93.3%), autoimmunity (12, 80%), and lymphoproliferation (10, 66.7%). The median (IQR) count of white blood cells (WBCs) and lymphocytes were 7160 (3690-12,600) and 3266 (2257-5370) cells/mm3, respectively. The median (IQR) absolute counts of CD3+ T lymphocytes and DNTs were 2085 (1487-4222) and 18 (11-36) cells/mm3, respectively. Low lymphocytes and low CD3+ T cells were observed in 3 (20%) patients compared to normal age ranges. Only one patient with FOXP3 mutation had DNT cells higher than the normal range for age. CONCLUSIONS: Most non-ALPS ALPID patients manifested normal DNT cell count. For a small subgroup of patients with high DNT cells, defects in other IEI genes may explain the phenotype and should be included in the diagnostic genetic panel.

Characterization of genes involved in the iron acquisition system of multidrug-resistant Acinetobacter baumannii.

Background: The high prevalence of virulence-associated genes observed in Acinetobacter baumannii isolates underscores the pathogenic potential of this bacterium. The presence of these genes confers enhanced survival, evasion of host defenses, and increased virulence. In this study, we investigate the presence and distribution of genes associated with virulence and assess the antimicrobial susceptibility patterns in clinical isolates of A. baumannii. Materials and method: This research focused on examining the 50 multi-drugs resistant (MDR) strains that were included in this investigation. The identification of these strains was validated using Oxa-51. The presence of the BauA and BasD genes was determined through conventional PCR techniques. Results: The results derived from Oxa-51 PCR confirmed the identification of all 50 selected strains of A. baumannii. Additionally, both the BauA and BasD genes were successfully identified in 82% of the MDR strains. Conclusion: Moreover, the varying antibiotic resistance patterns highlight the challenge in treating A. baumannii infections effectively. Strategies such as combination therapy, antimicrobial stewardship, and infection control measures should be considered to combat this multidrug-resistant pathogen.

The Radiological Manifestations of Phagocytic Primary Immunodeficiencies in Children.

Primary immunodeficiencies are a diverse group of rare genetic disorders, among which phagocytic dysfunction impairs neutrophil function in a wide range of inherited disorders. Due to the heterogeneity of the disorders a multidisciplinary approach is often required for early diagnosis and initiation of appropriate treatments. The aim of this study was to evaluate the imaging findings in children admitted with phagocytic primary immunodeficiencies. Thirty-five children who fulfilled the inclusion criteria for phagocytic dysfunction were enrolled in this study. The patients were under close observation and monitoring from January 2011 until data locking in December 2017. The diagnosis of phagocytic immunodeficiency was confirmed by the patient's clinical course, presentation features, and laboratory data.  Among the 35 patients studied, the most frequent condition was chronic granulomatous disease (CGD) (23 patients), followed by different types of neutropenia (8 patients) and Job's syndrome (4 patients). Mediastinal and hilar lymphadenopathies and consolidation were the most frequent presentations. There was a significant relationship between mediastinal/hilar lymphadenopathies and fungal infections. A meaningful relationship was also found between pulmonary nodules without halo signs in patients with concomitant tuberculosis and fungal infections. A significant correlation was found between CGD, pulmonary fibrotic changes, and mediastinal lymphadenopathies. The most frequent radiological manifestations in children included mediastinal and hilar consolidations. Physicians' awareness of the radiological and clinical manifestations of these inherited diseases may be helpful in the early diagnosis and timely initiation of specific prophylaxis measures to prevent infections and also to initiate hematopoietic stem cell transplantation as the curative management modality.

Acute Kidney Injury in Pediatric Patients with COVID-19; Clinical Features and Outcome.

INTRODUCTION: Renal disorders have been reported as the underlying cause as well as complications of critical COVID-19 in pediatric patients. The purpose of this study was to investigate the pattern of kidney involvement, particularly acute kidney injury (AKI), among pediatric patients with COVID-19. METHODS: In this prospective study, hospitalized pediatric patients with a clinical diagnosis of COVID-19 were enrolled. Demographic, clinical, and laboratory findings were collected and analyzed using a mixed method of qualitative and quantitative approaches and descriptive statistics. RESULTS: One hundred and eighty-seven patients, including 120 (64.2%) males and 67 (35.8%) females with COVID-19 with a median age (interquartile range) of 60 (24 to 114) months were enrolled in this study. Most patients (n = 108, 58.1%) had one or two underlying comorbidities, mainly malnutrition (77.4%), neurologic/learning disorders (21.4%), and malignancy (10.2%). According to the Kidney Disease Improving Global Outcomes (KDIGO) classification, AKI was detected in 38.5% of patients (stage 1: 55.6%, stage 2: 36.1%, and stage 3: 8.3%) at presentation or during hospitalization. Nine patients (4.8%) required hemodialysis and 16 (8.6%) eventually died. There was no significant association between AKI and admission to the pediatric intensive care unit (PICU) (P > .05), a multisystem inflammatory syndrome in children (MIS-C) (P > .05), comorbidities (P > .05), and mortality rate (P > .05). CONCLUSION: Kidneys are among the major organs affected by COVID-19. Although kidney abnormalities resolve in the majority of pediatric COVID-19 infections, particular attention should be paid to serum creatinine and electrolyte levels in patients affected by COVID-19, particularly children with a history of malnutrition and kidney disorders.  DOI: 10.52547/ijkd.7151.

Iranian Pediatric COVID-19 Epidemiology and Clinical Characteristics.

BACKGROUND: Despite the worldwide spread of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), information about the epidemiological and clinical patterns of this infection is still largely unknown in children. In addition, the prevalence of this disease is still very high in some parts of the world, including Iran. Thus, this study aims to evaluate the epidemiological features, laboratory and imaging findings, and the type of treatments in children with novel coronavirus 2019 (COVID-19). METHOD: This study is conducted from March 2020-March 2021 by using the medical records of hospitalized confirmed COVID-19 children younger than 18 years in five cities of Iran: Tehran, Ahwaz, Isfahan, Bandar-Abbas, and Khorramabad. In addition to demographic and epidemiological data, we also studied clinical signs and treatments. RESULTS: In total 278 confirmed COVID-19 children, the average age was 5.3 years, and 59.4%were boys. A total of 37.8% had an underlying disease, in which the most common was a malignancy. The most common symptoms were fever and cough. In this group of pediatrics, some abnormal laboratory findings have been seen. GGO (Ground-Glass Opacity) had been diagnosed in 58.6% of children. 3.6% needed oxygen therapy with ventilators, and 83.09% had received antibiotic treatments with the majority of ceftriaxone. Also, 10% had got steroids. In this study, the mortality rate was 4.3%. CONCLUSION: In this study, most of the children who died had an underlying disease, so timely care and action is important in them. Most children admitted to our study received antibiotics and were prescribed antivirals and steroids for a smaller number. Also, a small number of children received oxygen therapy, most of whom were in the age group of 1 to 5 years.

Severe Combined Immunodeficiency: A Case Series and Review from a Tertiary Pediatric Hospital.

Severe combined immunodeficiency syndrome (SCID) is a life-threatening condition leading to early infant death as a result of severe infection, due to impaired cellular and humoral immune systems. Various forms of SCID are classified based on the presence or absence of T cells, B cells and natural killer cells. Patients usually present with recurrent infections and failure to thrive. Definitive treatment is hematopoietic stem cell transplantation. To achieve the best outcome, it should be performed prior to the development of severe infection. In This study, we described 10 patients (6 male and 4 female) with SCID who were admitted to Mofid Children Hospital, Tehran, Iran, from 2006 to 2013. We reviewed patients' clinical manifestation, laboratory data, family history and outcome. The mean age at the time of diagnosis was 131.8 days. One patient had non-consanguineous parents. Seven patients received BCG vaccine before the diagnosis of SCID, three of them showed disseminated BCG infection. One patient presented with invasive pulmonary aspergillosis. Flow cytometric analysis showed T⁻B⁺NK⁻ in three patients, T⁻B⁻NK⁺ in five patients, T⁻B⁻NK⁻ in one patient, and T⁻B⁺NK⁺ in one patient. This study highlights the importance of early diagnosis and patient referral before the occurrence of serious infection.

Colonization with Clostridium difficile in Children with Cancer.

OBJECTIVE: Clostridium difficile is a gram-positive, anaerobic, spore-forming bacillus. Usually it does not cause disease unless a patient who is colonized with toxin-producing strains has been treated with antibiotics, particularly those that change the anaerobic flora of the large intestine. METHODS: We investigated in a prospective study intestinal colonization of C. difficile and its toxins in children with malignancy that used different antibiotics and cytotoxic drugs. FINDINGS: One hundred fifty-two patients were included in this prospective study. Stool samples were obtained within the first 48 hours after admission and cultured for C. difficile; cytopathic effect of C. difficile was detected on HELA cells, also ELISA test was performed for detection of toxins A and B. 25% of patients had positive culture for C. difficile; 36/38 (92%) revealed positive cytopathic effect on HELA cells. No significant relation was found between age, gender, history of antibiotic consumption and C. difficile positive culture and cytopathic effect on HELA cells. The only relation was seen between cotrimoxazol usage and cytopathic effect on HELA cells (P=0.03). CONCLUSION: Although the rate of C. difficile colonization (25.6%) and toxigenic strains (23.7%) in admitted children in hematologic ward is high, the rate of ELISA positive test for toxin A+B was not correspond with culture and cytopatic effect on HELA cell. With respect to sensitivity and specificity of ELISA test, possibility for existence of toxin C with cytopathic effect is high in this type of patients.

Aetiology of upper respiratory tract infections in children in Arak city: a community based study.

Viruses are frequent causes of upper respiratory tract infections in children. We investigated the viral aetiology of community-acquired upper respiratory tract infections (URIs) in young children treated as outpatients in community settings. During November 2008, nasal swab specimens were taken from children with recent onset of upper respiratory tract infections. The patients attended day care or primary schools; the specimens were randomly obtained by pediatricians from schools and childcare institutions and sent for identification by PCR method. A total of 300 specimens were collected. From all samples, 40.67% were positive for at least 1 virus, viz. adenovirus 11.76%, rhinovirus 9.8%, respiratory syncytial virus 6.08%, influenza virus 5.56%, parainfluenza virus 4.9%, enterovirus 2.94% and a combination of 2 viruses 2%. Clinical manifestations of the respiratory infections were as follows: 70.7% of the patients had coryza, 69.3% cough, 26% sneezing, 19.7% sore throat, 2.7% headache, 7.7% fever, 2.3% conjunctivitis, 1.3% abdominal pain and 1% hoarseness. The results of this study demonstrate that adenoviruses and rhinoviruses are the two most common viral agents isolated from pediatric outpatients with acute URIs in autumn in Arak City. Coryza and cough were the most common symptoms in children. Sore throat and hoarseness were more prevalent in infections caused by influenza virus, conjunctivitis in parainfluenza, and coryza in rhinovirus infections.

Urinary interleukin-8 in acute pyelonephritis of children: a before-after study.

INTRODUCTION: The aim of this study was to assess urinary interleukin-8 (IL-8) levels in pyelonephritis and its relation with the clinical course of the infection and of inflammatory changes detected by renal scintigraphy. MATERIALS AND METHODS: In this quasi-experimental before-after study, we evaluated 91 children aged 1 to 144 months (mean 34.4 +/- 35.2 months) with pyelonephritis. Inflammatory markers including erythrocyte sedimentation rate, C-reactive protein, leukocyte count, and urinary IL-8, together with the results of ultrasonography, voiding cystourethrography, and dimercaptosuccinic acid renal scintigraphy were evaluated in these children. The ratios of urinary IL-8 to creatinine (IL-8/C) before and after the treatment were compared with each other. RESULTS: Urinary IL-8/C levels were significantly higher after the empirical treatment in comparison with those before the treatment (0.19 +/- 0.21 versus 0.51 +/- 0.53, P < .001). No correlation was found between the urinary IL-8 levels and leukocyturia, urine culture results, other inflammatory markers, or findings of imaging examinations. CONCLUSIONS: We found high urinary IL-8 levels in children with pyelonephritis. We also documented its increasing after the treatment. We conclude that evaluation of urinary IL-8 can be a noninvasive test for diagnosis of upper urinary tract infection and its response to treatment.