Inborn Errors of Immunity in Pediatric Intensive Care: Prevalence, Characteristics, and Prognosis.

Inborn errors of immunity (IEI) are a heterogeneous group of genetic diseases characterized by impaired immune system function. This prospective study aimed to determine the frequency, characteristics, and clinical course of IEI patients admitted to the pediatric intensive care unit (PICU) and identify mortality-related factors. Using a comprehensive immunological evaluation protocol, we screened 753 PICU admissions for potential IEIs during three years. Patients with pre-existing IEI diagnoses, chronic diseases, ongoing chronic medication regimens, other known comorbidities, trauma cases, post-surgical cases, and poisonings were excluded. Thirty-three patients were newly diagnosed with IEIs during or as a result of their PICU stay, representing an incidence of 4.39%. The most common disorders were immunodeficiencies with immune dysregulation (48.5%), followed by combined immunodeficiencies (24.2%). Severe viral infections (61%) and life-threatening infections (51.7%) were the most frequent warning signs. Only 31% of patients exhibited at least two Jeffrey Modell Foundation warning signs. The mortality rate was 58%, highlighting the need for early diagnosis and treatment. Newborn screening and family segregation studies are crucial to improving outcomes for IEI patients in intensive care settings.

Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis.

OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.

Associations Between Transcranial Doppler Flow Velocities, Laboratory Parameters, and Clinical Features in Turkish Children With Sickle Cell Disease.

OBJECTIVE: Stroke is one of the major complications of sickle cell disease (SCD). Stroke features either occlusion of, or stenosis at, the origin of one of the large intracerebral arteries, the internal carotid artery (ICA), and/or the middle cerebral artery (MCA). PURPOSE: We sought correlations between cerebral blood flow velocities and the laboratory and clinical findings of patients with SCD. MATERIALS AND METHODS: Fifty-three pediatric SCD patients (39 with HbSS, 14 with HbSß0) were analyzed. The mean patient age was 12.9±3.9 years. The control group contained 24 healthy individuals. The time-averaged maximum mean velocity (TAMMV) and resistive index (RI) of the MCA, the TAMMVs of the ICA and vertebral artery (VA), and the diameter of the VA were estimated through transcranial Doppler ultrasonography using a 2.5 MHz transducer, in accordance with the Stroke Prevention Trial in Sickle Cell Anemia (STOP) protocol. We evaluated the relationships between the TAMMVs, laboratory parameters, and clinical findings. RESULTS: The mean±SD MCA TAMMV was 161.2±35.4 cm/s in patients with HbSS and 185.8±62.9 cm/s in patients with HbSß0. The mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 168.5±43.9 cm/s, 0.63±0.06, 116.8±25.5 cm/s, 69.2±18.5 cm/s, and 3.5±0.61 mm for all SCD patients, respectively. In the control group, the mean MCA TAMMV, RI, ICA TAMMV, VA TAMMV, and VA diameter were 103.8±28.8 cm/s, 0.53±0.04, 96.4±27.8 cm/s, 40.3±12.1 cm/s, and 3.4±0.6 mm, respectively. Although the differences were not significant, TAMMVs were higher in HbSß0 patients taking hydroxyurea; those with hemoglobin levels <8 g/dL, ferritin levels >1000 ng/dL, mean platelet volume >12 fL, or red cell distribution width >18%; or required chelation, or were below the third percentiles of weight and height. The TAMMV was significantly higher only in SCD patients who complained of headache. CONCLUSIONS: High ferritin and low hemoglobin levels, a high mean platelet volume, a high red cell distribution width, low weight (below the third percentile), and a short height (below the third percentile) may be associated with elevated cerebral blood flow velocities and an increased stroke risk in children with SCD. Children with such features should be closely followed-up through transcranial Doppler ultrasonography examination.

Common viral respiratory infections in children with cancer during the COVID-19 pandemic: a multicenter study from Türkiye.

BACKGROUND: Microbiologic confirmation of respiratory tract infections gained importance during the coronavirus disease 2019 (COVID-19) pandemic. This study retrospectively evaluated seasonal distribution, clinical presentation, and complications of respiratory viral infections (RVIs) other than COVID-19 in children with cancer during and after the pandemic lockdown. METHODS: Two hundred and sixty-five inpatient and outpatient RVI episodes in 219 pediatric cancer patients confirmed by multiplex reverse transcriptase polymerase chain reaction (RT-PCR) panels from 13 centers were enrolled. RESULTS: Eighty-six (32.5%) of the total 265 episodes occurred in 16 months corresponding to the lockdowns in Türkiye, and the remaining 67.5% in 10 months thereafter. Human rhinovirus/enterovirus (hRE) (48.3%) was the most common agent detected during and after lockdown. Parainfluenza virus (PIV) (23.0%), influenza virus (9.8%), and respiratory syncytial virus (RSV) (9.1%) were the other common agents. The 28.7% of episodes were lower respiratory tract infections (LRTIs), and complications and mortality were higher than upper respiratory tract infections (URTIs) (25.0% vs 5.3%). Bacteremia was identified in 11.5% of culture-drawn episodes. Treatment delay in one-third and death within four weeks after RVI in 4.9% of episodes were observed. CONCLUSION: During the pandemic, fewer episodes of RVIs occurred during the lockdown period. Respiratory viruses may cause complications, delays in treatment, and even death in children with cancer. Therefore, increased awareness of RVIs and rapid detection of respiratory viruses will benefit the prevention and, in some cases, abrupt supportive and some antiviral treatment of RVI in children with cancer.

A Boy with 46,XX Karyotype (SRY double-positive) having a Leydig Cell Tumor.

Leydig cell tumors are the most common type of testicular sex cord stromal tumors. Presence of Y chromosome is associated with tumor risk in sex development disorder (DSD), however tumor development without Y chromosome are extremely rare. A 16-year-old boy diagnosed with Leydig cell tumor due to a mass in the right testis was referred after the right orchiectomy. In physical examination, left testis was 10 ml, and a labium residue in penoscrotal region with bilateral gynecomastia was present. Karyotype was 46,XX, and SRY was double-positive in FISH analysis. Ifosfamide, carboplatin and etoposide chemotherapy was initiated due to Leydig cell tumor. Here, we report the first pediatric case having 46,XX, SRY double-positive testicular DSD with Leydig cell tumor.

Neuroimaging Findings in Pediatric Patients with Thalassemia Major.

BACKGROUND: Cranial magnetic resonance imaging (MRI) studies about iron accumulation in children with thalassemia major are quite limited. AIM: This study aimed to detect neurological findings with cranial MRIs in the pediatric patients with thalassemia major who did not develop any neurological complications. MATERIALS AND METHODS: Pediatric patients with thalassemia major who followed in the Pediatric Hematology Unit between 1 July 2017 and 1 January 2019 were included in the study. The patients underwent cranial MRI scans. RESULTS: A total of 30 patients were included. The median age was 15 (range from 4-18) years old. We found that 7 patients had a splenectomy and 19 of the remaining 23 patients had splenomegaly. In addition, 13 of the patients had hepatomegaly, 10 had skeletal deformities, and 17 had growth retardation. The mean ferritin level was 3772.3 ± 2524.8. We detected various pathologies on cranial MRI images of 10 (33.3%) patients. In 3 of these patients, millimeter-sized ischemia-compatible lesions were found in the cerebral white matter, which did not fit any arterial area, and 5 patients had hyperintense lesions in the basal ganglia. CONCLUSION: Our study is valuable since 1/3 of our pediatric patients with thalassemia major were detected with intracranial pathology.

Risk factors for candidemia in pediatric intensive care unit patients.

OBJECTIVE: To determine the risk factors for developing candida infections in pediatric intensive care unit (PICU). METHODS: The present study was conducted as a case-control study and included the population of patients who were admitted to PICU during the period of March 2010-March 2011. RESULTS: During the study period, a total of 57 patients in PICU had candidemia, 4 cases were excluded due to their PICU stay less than 48 h and one due to the insufficient data. The most commonly isolated Candida species was C. albicans, followed by C. parapsilosis. The median duration of hospitalization in PICU was higher (22.0 d) in candidemia patients compared to control group (13.5 d) (p = 0.037). The patients with candidemia had higher rates of presence of mechanical ventilation, presence of central venous catheter, and being under total parenteral nutrition; compared to the control group. CONCLUSIONS: The longer PICU durations, mechanical ventilation, central venous catheter, total parenteral nutrition were the associated factors. Although trials for predicitive models or scoring systems for development of candidemia have been performed; more future studies were required for practical usage in clinics settings in order to prevent candidemia.