Infant Intensive Care Unit: Is it Time to Change?

OBJECTIVES: To assess the effect of the Infant intensive care unit (InICU), a specialized unit for critically ill infants established in 2016 in authors' hospital, on infant mortality and compare the outcome with the current Pediatric intensive care units (PICU). METHODS: In this retrospective cross-sectional study, two groups were defined; the first included expired patients aged 1 mo to 2 y admitted to PICU before the establishment of the InICU (the PICU group). The second included age-matched expired patients admitted to the InICU (the InICU group). Data were recorded using a questionnaire. RESULTS: The authors found that the age, sex, underlying diseases, the leading cause of admission to the ICU, time of death, hospital and ICU length of stay, and the pediatric index of mortality 2 (PIM 2) score were same between the two groups. The incidence of mortality in the PICU group was 10.66 in 1000 person-month. This value was 6.37 for the InICU group (P-value <0.001). The relative risk of mortality of patients admitted to the PICU group compared to the InICU group was 1.67 (P-value <0.001). CONCLUSIONS: Establishment of age specific InICU for infants may be beneficial in reducing infant mortality.

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.

Clinical Effects of COVID-19 on Hematopoietic Stem Cell Transplant Outcomes in Pediatric Patients.

Coronavirus disease 2019 is the third zoonotic acute respiratory disease after SARS virus and Middle East respiratory syndrome. Most cases are mild in healthy children. In contrast, the infection is more severe in patients with underlying health conditions. Because there are few posttransplant reports in hematopoietic stem celltransplant patients, here we described COVID19 infection in 4 confirmed cases among pediatric hematopoietic stem cell transplant recipients: 3 boys and 1 girl with a median age of 6 years. Three patients presented with symptoms of lower respiratory tract disease, whereas 1 patient presented with extrapulmonary symptoms without fever or pulmonary involvement. All of the patients were on immunosuppressivedrugs, ie, 1patientforgraft-versus-hostdisease prophylaxis and 3 patients for graft-versus-host disease treatment.Thosewhowerediagnosedwith active graftversus-hostdisease requiredmechanical ventilationand intensive care. Two patients died from multiple organ dysfunction and resistant coinfection, and 1 patient developed pulmonary hypertension and mild cardiomegaly and remained at the hospital for more than 2 months, whereas the patient with no graft-versus-host disease was discharged and recovered. Our findings showed that COVID-19 infection among hematopoietic stem cell transplant recipients may be more severe and associatedwithlong-termhospitalization and complications. Active graft-versus-hostdisease, coinfections, and long-term use of immunosuppressive agents are risk factors for poor outcomes.

Catastrophic Brain Aspergillosis after Liver Transplantation.

Background. Liver transplantation has many complications. Because of receiving immunosuppressive regimens, infectious complications in these patients may have fatal results. Aspergillosis in solid organ recipients is one of the most common fungal infections that usually occur 1 month after transplantation. Aspergillus infection mainly involves the lungs. Although the central nervous system may get involved due to hematogenous spreading from lungs, isolated central nervous system involvement is rarely reported. Case Presentation. The patient was an 8-year-old boy, with a case of Wilson disease, who underwent liver transplantation due to acute fulminant hepatic failure. Four days after the surgery, he was affected by fever, agitation, loss of consciousness, hemiparesis, and focal seizure. Brain MRI showed abscess formation, whereas chest X-ray was normal. Intravenous antibiotics were initiated but the patient's condition was not improving; therefore, surgical drainage of the abscess was performed. The pathological investigation was compatible with aspergillosis. Antifungal therapy with voriconazole was administrated. His symptoms were resolved but unfortunately, brain lesions caused persistent vegetative state. Discussion. Aspergillus is a ubiquitous organism that mainly occurs in immunocompromised patients. Aspergillosis could be prevented by environmental modification such as installing high-efficiency particulate air filters. Chemoprevention with triazoles, echinocandins, and polyenes is also effective. Voriconazole is the drug of choice for aspergillosis treatment. Although voriconazole is a highly effective antifungal drug, cerebral aspergillosis is often fatal.

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency.

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents.

A Randomized Clinical Trial Evaluating the Efficacy of Colistin Loading Dose in Critically Ill Children.

OBJECTIVE: Pharmacokinetic and clinical studies recommend applying loading dose of colistin for the treatment of severe infections in the critically ill adults. Pharmacokinetic studies of colistin in children also highlight the need for a loading dose. However, there are no clinical studies evaluating the effectiveness of colistin loading dose in children. METHODS: In a randomized trial, children with ventilator-associated pneumonia or central line-associated bloodstream infection (CLABSI) for whom colistin was initiated, were enrolled. Patients were randomized into two groups; loading dose and conventional dose treatment arms. In the conventional treatment arm, colistimethate sodium was initiated with maintenance dose. In the loading dose group, colistimethate sodium was commenced with a loading dose of 150,000 international unit/kg, then on the maintenance dose. Both treatment arms also received meropenem as combination therapy. Primary outcomes were overall efficacy, clinical improvement and microbiological cure. Secondary outcomes were colistin-induced nephrotoxicity and development of resistance. FINDINGS: Thirty children completed this study. There was a significantly higher overall efficacy in the group received loading dose (42.9 vs. 6.3%, P = 0.031). There weren't any significant differences in the clinical and microbiological endpoints. In the subgroup of children with CLABSI, results illustrated a trend toward (though statistically nonsignificant) better clinical cure for patients receiving loading dose. CONCLUSION: This preliminary study suggests that colistin loading dose might have some benefits in critically ill children, specifically in children with CLABSI. Further trials are required to elucidate colistin best dosing strategy in critically ill children with severe infections.

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.