Whole-exome sequencing to identify undiagnosed primary immunodeficiency disorders in children with community-acquired sepsis, admitted in the pediatric intensive care unit.

BACKGROUND: Whole-exome sequencing (WES) provides a powerful diagnostic tool for identifying primary immunodeficiency diseases (PIDs). This study explores the utility of this approach in uncovering previously undiagnosed PIDs in children with community-acquired sepsis (CAS), with a medical history of recurrent infections or a family history of PIDs. METHODS: We performed WES on DNA samples extracted from the blood of the 34 enrolled patients, followed by bioinformatic analysis for variant calling, annotation, and prioritization. We also performed a segregation analysis in available family members to confirm the inheritance patterns and assessed the potential impact of the identified variants on protein function. RESULTS: From 34 patients enrolled in the study, 29 patients (85%) with previously undiagnosed genetic diseases, including 28 patients with PIDs and one patient with interstitial lung and liver disease, were identified. We identified two patients with severe combined immunodeficiency (SCID), patients with combined immunodeficiency (CID), six patients with combined immunodeficiency with syndromic features (CID-SF), four patients with defects in intrinsic and innate immunity, four patients with congenital defects of phagocyte function (CPDF), and six patients with the disease of immune dysregulation. Autoinflammatory disorders and predominantly antibody deficiency were diagnosed in one patient each. CONCLUSION: Our findings demonstrate the potential of WES in identifying undiagnosed PIDs in children with CAS. Implementing WES in the clinical evaluation of CAS patients with a warning sign for PIDs can aid in their timely diagnosis and potentially lead to improved patient care.

COVID-19 Pandemic Experiences in Pediatric Intensive Care Unit: An Iranian Referral Hospital-Based Study.

Introduction: In late February 2020, after we had informed about the presence of some cases of COVID-19 in Iran and its rapid spread throughout the country, we decided to make the necessary arrangements for patients with critical conditions in Pediatric Intensive Care Unit (PICU) at Children's Medical Center. There are a little data on critically ill children with COVID-19 infection with ICU requirements. The aim of this study was to describe clinical characteristics, laboratory parameters, treatment, and outcomes of the pediatrics population infected by SARS-CoV-2 admitted to PICU. Materials and Methods: This study was performed between February 2020 and May 2020 in the COVID PICU of the Children's Medical Center Hospital in Tehran, Iran. Patients were evaluated in terms of demographic categories, primary symptoms and signs at presentation, underlying disease, SARS-CoV-2 RT-PCR test result, laboratory findings at PICU admission, chest X-ray (CXR) and lung CT findings, and treatment. Moreover, the need to noninvasive ventilation (NIV) or mechanical ventilation, the length of hospital stay in the PICU, and outcomes were assessed. Results: In total, 99 patients were admitted to COVID PICU, 42.4% (42 patients) were males, and 66 patients had positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR). There was no statistically significant difference in the frequency of clinical signs and symptoms (except for fever) among patients with positive SARS-CoV-2 RT-PCR and negative ones. Among all admitted patients, the presence of underlying diseases was noticed in 81 (82%) patients. Of 99 patients, 34 patients were treated with NIV during their admission. Furthermore, 35 patients were intubated and treated with mechanical ventilation. Unfortunately, 11 out of 35 mechanically ventilated patients (31%) passed away. Conclusion: No laboratory and radiological findings in children infected with COVID-19 were diagnostic in cases with COVID-19 admitted to PICU. There are higher risks of severe COVID-19, PICU admission, and mortality in children with comorbidities.

Fatal invasive aspergillosis in a child with chronic granulomatous disease.

Patients with chronic granulomatous disease, a primary immunodeficiency, experience granulomatous complications and recurrent life-threatening opportunistic bacterial and fungal infections. In this article, we report on a case of invasive aspergillosis in an eight-year-old boy with chronic granulomatous disease, who presented with pleural effusion and pneumonia, cerebral venous sinus thrombosis, and unusual skin lesions caused by Aspergillus fumigatus. Antifungal treatment with itraconazole and other antifungal agents, along with interferon-γ, was ineffective and the patient eventually died from cerebral venous sinus thrombosis, and intracerebral haemorrhage following increased intracranial pressure after one month. The diagnosis of invasive aspergillosis should be considered early in children presenting with invasive fungal infections, particularly those involving the central nervous system.

Validity of Pediatric Early Warning Score in Predicting Unplanned Pediatric Intensive Care Unit Readmission.

Despite the fact that unscheduled readmission to pediatric intensive care units (PICUs) has significant adverse consequences, there is a need for a predictive tool appropriate for use in the clinical setting. The aim of this study was to assess the ability of the modified Brighton pediatric early warning score (PEWS) to identify children at high risk for early unplanned readmission. In this retrospective cohort study, all patients aged 1 month to 18 years of age discharged from PICUs of two tertiary children's hospitals during the study interval were enrolled. Apart from demographic data, the association between PEWS and early readmission, defined as readmission within 48 hours of discharge, was analyzed by multivariable logistic regression. From 416 patients, 27 patients had early PICU readmission. Patients who experienced readmission were significantly younger than the controls. (≤12 months, 70.4 vs. 39.1%, p = 0.001) Patients who were admitted from the emergency room (66.7 and 33.3% for emergency department (ED) and floor, respectively, p = 0.012) had higher risk of early unplanned readmission. PEWS at discharge was significantly higher in patients who experienced readmission (3.07 vs. 0.8, p < 0.001). A cut-off PEWS of 2, with sensitivity 85.2% and specificity 78.1%, determined the risk of unplanned readmission. Each 1-point increase in the PEWS at discharge significantly increases the risk of readmission (odds ratio [OR] = 3.58, 95% confidence interval [CI]: [2.42-5.31], p < 0.001). PEWS can be utilized as a useful predictive tool regarding predicting unscheduled readmission in PICU. Further large-scale studies are needed to determine its benefits in clinical practice.

Alteration of Plasma Amino Acid Concentrations in Iranian Children with COVID-19.

COVID-19 is an acute viral disease that has so far infected more than 200 million and killed more than four million worldwide. It affects the immune system and other organs. Here, we investigated the level of free plasma amino acids in COVID-19 patients and compared them with non-COVID-19 subjects. We also compared amino acids levels in critically ill patients admitted to the intensive care unit (ICU) with non-ICU patients and expired and recovered patients. Twenty-six COVID-19 patients and 32 non-COVID-19 subjects were included in the study. The mean of glutamic acid, serine, glycine, threonine, phenylalanine, leucine, lysine, alanine, arginine, aspartic acid, and ornithine was significantly higher in cases than controls. In addition, the mean of glutamine was significantly lower in patients than controls (443.89 ± 254.31 vs. 651.73 ± 107.38, PV < 0.001). Low level of glutamine and isoleucine was seen in the majority of ICU and expired patients, respectively. Logistic regression analysis showed low level of isoleucine as a predictor variable in mortality (P = 0.02, EXP (B) = 16.5, and CI 95% = (1.48, -183.07)). There was a positive and significant relationship between some amino acids levels, serum liver enzymes, and sodium concentrations. There was also a significant but negative correlation between histidine levels, ESR, and ferritin. Phenylalanine had a highly positive relationship with serum procalcitonin in patients (R 2 = 0.534, PV = 0.015). Our studies have shown the alteration of plasma amino acids concentration in COVID-19 patients. These changes are more evident in critically ill and at-risk patients.

Disseminated Leishmaniasis Due to Using Immunosuppression Drugs: A Case Report.

Visceral leishmaniasis is a common parasitic disease between humans and animals, transmitted by sandflies (Phlebotomus) in the Mediterranean countries, including Iran. The statistics have been reported less than real due to errors in the diagnosis and reporting of affected cases. In this report, we will present the symptoms and manifestations of this disease to reduce late detection and exacerbating factors. The patient was a three-year-old girl from Tehran, Iran who had ascites and hepatomegaly. When she was 9 month-old, she was diagnosed as autoimmune hepatitis after liver biopsy and she was treated with immunosuppressive drugs (Azathioprine, prednisolone, and cyclosporine) for 22 months, but later she suffered from fever, pancytopenia, and hepatosplenomegaly. Then a bone marrow biopsy was done for her. There was a large amount of Leishman body in her bone marrow and treatment for Kala-azar was started for her. In patients with prolonged fever and splenomegaly, especially association with pancytopenia, consider leishmaniasis. Immunosuppressive drugs can disseminate parasitic diseases, including visceral leishmaniasis.

Caustic Agent Ingestion by a 1.5-Year-Old Boy.

We present a case of caustic ingestion by a 1.5-year-old boy. The caustic agent was drain opener which is a strong alkaline substance. Children in Iran and many other countries are still exposed to not "child proof" (child resistant packaging) toxic substance containers. Ingestion of caustic agents may lead to necrosis, perforation, and strictures. Substances that are ingested more frequently are liquid alkali material which causes severe, deep liquefaction necrosis. Common signs and symptoms of caustic agents are vomiting, drooling, refusal to drink, oral burns, stridor, hematemesis, dyspnea, dysphagia and abdominal pain. Even if no oropharyngeal lesion is seen, a significant esophageal injury which can lead to perforation and stricture cannot be ruled out. If abdominal pain or rigidity, substernal, chest or back pain exists, visceral perforation should be considered. The first thing to be checked is airway assessment. A lot of patients should be admitted to intensive care unit, and endoscopic evaluation, surgical intervention, long-term hospitalization, and worsening quality of life or among the complications. Preventive measures especially at the country level and approving proper legislation for obligating the related industries to produce child proof containers for house hold toxic products are the urgent measures to be followed by all of us.

A 15-Month-Old Boy With Respiratory Distress and Parapharyngeal Abscess: A Case Report.

Parapharyngeal abscess is a life-threatening disease. Upper respiratory tract infection is the main cause in children. We present a 15-month-old boy admitted to the emergency ward with the chief complaint of difficulty in breathing caused by parapharyngealabscess. His condition deteriorated gradually, and he transferred to the operation theater quickly for abscess drainage and because of the difficulty in orotracheal intubation; a tracheostomy was performed. His respiratory condition deteriorated 2 days after PICU admission, and the medical team noticed an unexplainable respiratory distress. A chest x ray obtained and showed a right side pneumothorax and subcutaneous emphysema around theneck area. The case presented here, had not been diagnosed at the first examination; however, there were enough clinical clues (such as respiratory distress, drooling, torticollis, bulging of theneck, previous viral respiratory infection, possible pharyngeal trauma). The story of this case reminds us the importance of the precise physical exam and history taking which could be life-saving.

Be careful of lies: a six-year-old boy with respiratory distress and decreased level of consciousness.

We reports a six-year-old child with autistic disorder and methadone intoxication. Developmental disorders may mislead the caretakers and doctors to interpret the clinical manifestation and behavioral changes of these patients. Methadone indigestion can be fatal in children even in a tiny amount and cardiac monitoring should be performed at least for the first 24 hours. The pervasive prescription of methadone for detoxification programs and its extensive availability at homes of the addicted parents should point parents, doctors and media to pay more attention to provide safe-home environment for children. 

Apparent life-threatening events in neonatal period: clinical manifestations and diagnostic challenges in a pediatric referral center.

OBJECTIVE: Apparent Life-Threatening Events (ALTEs) is an episode that is frightening to the observer and is characterized by some combination of apnea, color change, altered muscle tone, choking, and gagging. This study was designed to evaluate and follow up neonates who presented with clinical manifestation of an ALTE in a year. METHODS: In this prospective observational study, all of the neonates with episode of ALTE who were admitted to the Children's Medical Center (CMC) in Tehran, from June 15(th) 2010 to May 14(th) 2011 were enrolled in the study. Data from patients consisting of history, physical examinations, and paraclinical findings were recorded in a checklist and all followed up 3 to 6 months after discharge. FINDINGS: During the study period 18 neonates were admitted due to ALTE episode(s) with mean age of 15±13 days. Nine (50%) neonates had previous attacks of ALTE. The most frequent complaint was cyanosis in 12 (67%) and apnea in 8 (44%) patients. In 10 (56%) the event lasted less than one minute, 13 (72%) were awake, 17 (95%) in supine position and 13 (72%) on their parent's lap. Primary antagonistic impression on admission was sepsis in 11 (61%) and concomitant seizure in 5 (28%). The most common final diagnosis according to repeated physical examinations, result of paraclinical investigations and follow up was sepsis 4 (22%) and aspiration 9 (50%). ALTE recurred in none of the neonates during follow up. CONCLUSION: The rate of ALTE seems to be higher than in this study owing to high incidence of recurrent ALTE. Although most of these attacks regress spontaneously, more attention should be paid for the underlying diseases.