Skeletal Muscle Mass Assessment in Pediatric Patients: Development of a Normative Equation and Assessment of Factors Associated With a Low Skeletal Muscle Mass in PICU Patients.

OBJECTIVES: To develop an equation for defining a low skeletal muscle mass (SMM) in children and to investigate risk factors and outcomes associated with low SMM in critically ill pediatric patients. DESIGN: Single-center retrospective pediatric cohorts, 2011-2018. SETTING: Tertiary Emergency and Critical Care Center of Kyushu University Hospital in Japan. PATIENTS: We studied two cohorts of pediatric patients 1-15 years old who underwent abdominal CT at the level of the third lumbar vertebra (L3). First a cohort of trauma patients presented to the emergency department in whom we developed an SMM regression equation. Second, a cohort of patients who had undergone abdominal CT within 3 days of PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The equation for estimating normal SMM used sex, age, and weight. Low SMM was defined as less than 80% of normal. In the 112 patients in the PICU cohort, median (range) age was 68 (13-191) months, and 83 (74.1%) had underlying disease. There was low SMM in 54 patients (48.2%). Regarding associations, using odds ratio (OR) and 95% CI, we found that low dietary intake (OR 4.33 [95% CI, 1.37-13.70]; p = 0.013) and the presence of underlying disease (OR 7.44 [95% CI, 2.10-26.30]; p = 0.002) were independently associated with greater odds of low SMM. Low SMM, compared with normal SMM, was also associated with longer hospital stays (42.5 d vs. 20.5 d; p = 0.007; ß, 1.59; 95% CI, 1.09-2.33; p = 0.016). CONCLUSIONS: In this retrospective PICU cohort from a single center in Japan, we found that low SMM at PICU admission was present in almost half the cases. Low SMM, as defined by being less than 80% of the normal, was associated with greater odds of low dietary intake and underlying chronic disease. Furthermore, low SMM was associated with longer hospital stays.

Rapid and long-lasting efficacy of high-dose ambroxol therapy for neuronopathic Gaucher disease: A case report and literature review.

Gaucher disease (GD) is a lysosomal storage disorder caused by a deficiency in the GBA1-encoded enzyme, ß-glucocerebrosidase. Enzyme replacement therapy is ineffective for neuronopathic Gaucher disease (nGD). High-dose ambroxol has been administered as an alternative treatment for a group of patients with nGD. However, little is known about the clinical indication and the long-term outcome of patients after ambroxol therapy. We herein report a case of a female patient who presented with a progressive disease of GD type 2 from 11 months of age and had the pathogenic variants of p.L483P (formerly defined as p.L444P) and p.R502H (p.R463H) in GBA1. A combined treatment of imiglucerase with ambroxol started improving the patient's motor activity in 1 week, while it kept the long-lasting effect of preventing the deteriorating phenotype for 30 months. A literature review identified 40 patients with nGD, who had received high-dose ambroxol therapy. More than 65% of these patients favorably responded to the molecular chaperone therapy, irrespective of p.L483P homozygous, heterozygous or the other genotypes. These results highlight the long-lasting effect of ambroxol-based chaperone therapy for patients with an expanding spectrum of mutations in GBA1.

High-Titer Anti-ZSCAN1 Antibodies in a Toddler Clinically Diagnosed with Apparent Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome.

Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain. The patient had a high titer of anti-ZSCAN1 antibodies (348; reference range < 40), and the increased values did not decline after acute phase treatment. Other encephalitis-related antibodies, such as the anti-NDMA antibody, were not detected. The rapid progression from obesity onset to central hypoventilation with encephalitis warns about the severe consequences of early-onset ROHHAD syndrome. These data indicate that serial measurements of anti-ZSCAN1 antibodies might be useful for the diagnosis and estimation of disease severity. Further research is needed to determine whether it can predict the clinical course of ROHHAD syndrome and whether there is any difference in antibody production between patients with and without tumors.

Persistent intracranial hyper-inflammation in ruptured cerebral aneurysm after COVID-19: case report and review of the literature.

BACKGROUND: The systemic manifestations of coronavirus disease 2019 (COVID-19) include hyperinflammatory reactions in various organs. Recent studies showed evidence for the frequent involvement of central nervous system in affected patients; however, little is known about clinical features of cerebrovascular diseases in childhood-onset COVID-19. CASE PRESENTATION: A 10-year-old boy recovered from SARS-CoV-2 infection without complication. On 14 days after infection, he presented with loss of consciousness. A head computed tomography detected a ruptured cerebral aneurysm at the left posterior cerebral artery accompanying subarachnoid hemorrhage (SAH). Immediate surgical intervention did not rescue the patient, resulting in the demise 7 days after admission. Serological and genetic tests excluded the diagnosis of vasculitis and connective tissue disorders. Retrospective analysis showed markedly higher levels of interleukin (IL)-1ß, IL-6 and IL-8 in the cerebrospinal fluid than the serum sample concurrently obtained. A review of literature indicated that adult patients with COVID-19 have a risk for the later development of SAH during the convalescent phase of COVID-19. CONCLUSIONS: SAH is a severe complication of COVID-19 in children and adults who have asymptomatic cerebrovascular aneurysms. The markedly high levels of cytokines detected in the cerebrospinal fluid suggested that intracranial hyperinflammatory condition might be one of the possible mechanisms involved in the rupture of a preexisting cerebrovascular aneurysms.

Pretransplant ribavirin and interferon-α therapy for rhinovirus interstitial pneumonia in a RAG1-deficient infant.

Severe combined immunodeficiency (SCID) is one of the most serious inborn errors of immunity leading to a fatal infection in early infancy. Allogeneic hematopoietic cell transplantation (HCT) or elective gene therapy prior to infection or live-attenuated vaccination is the current standard of curative treatment. Even in the era of newborn screening for SCID, pretransplant control of severe infection is challenging for SCID. Multiple pathogens are often isolated from immunocompromised patients, and limited information is available regarding antiviral strategies to facilitate curative HCT. We herein present a case of successfully controlled pretransplant pneumonia after ribavirin and interferon-α therapy in an infant with RAG1-deficiency. A four-month-old infant presented with severe interstitial pneumonia due to a co-infection of rhinovirus and Pneumocystis jirovecii. The tentative diagnosis of SCID prompted to start antibiotics and trimethoprim-sulfamethoxazole on ventilatory support. Because of the progressive respiratory failure four days after treatment, ribavirin and then pegylated interferon-α were started. He showed a drastic response to the treatment that led to a curative HCT 32 days after admission. This patient received the genetic diagnosis of RAG1-deficiency. Currently, he is an active 3-year-old boy with normal growth and development. The review of literature indicated that rhinovirus had a comparable or rather greater impact on the mortality of pediatric patients than respiratory syncytial virus. Considered the turn-around time to the genetic diagnosis of SCID, prompt ribavirin plus interferon-α therapy may help to control severe rhinovirus pneumonia and led to the early curative HCT for the affected infants.

Critical vitamin deficiencies in autism spectrum disorder: Reversible and irreversible outcomes.

Vitamin deficiencies are an emerging concern in the management of children with autism spectrum disorder (ASD). Particular attention is required for recognizing the variable signs caused by unbalanced food intakes. We herein report two patients with multiple vitamin deficiencies who needed critical care showing different prognoses. Patient 1 with 'Shoshin' beriberi presenting with cardiac arrest had thiamine deficiency developed severe neurological sequelae despite rapid vitamin supplementation. Patient 2, who had leg pain and a limping gait, showed a rapid recovery with intravenous infusion and tube feeding after being diagnosed with scurvy. A literature search revealed several children with ASD with critically ill thiamine deficiency, but few reports documented a life-threatening condition in the form of cardiac arrest at the onset. Considering the high observation rate of food selectivity in children with ASD, early intervention is required to prevent the exacerbation of vitamin deficiencies to severe neurological disabilities.

Predictive values of early head computed tomography for survival outcome after cardiac arrest in childhood: a pilot study.

Predicting outcomes of children after cardiac arrest (CA) remains challenging. To identify useful prognostic markers for pediatric CA, we retrospectively analyzed the early findings of head computed tomography (CT) of patients. Subjects were non-traumatic, out-of-hospital CA patients < 16 years of age who underwent the first head CT within 24 h in our institute from 2006 to 2018 (n = 70, median age: 4 months, range 0-163). Of the 24 patients with return of spontaneous circulation, 14 survived up to 30 days after CA. The degree of brain damage was quantitatively measured with modified methods of the Alberta Stroke Program Early CT Score (mASPECTS) and simplified gray-matter-attenuation-to-white-matter-attenuation ratio (sGWR). The 14 survivors showed higher mASPECTS values than the 56 non-survivors (p = 0.035). All 3 patients with mASPECTS scores ≥ 20 survived, while an sGWR ≥ 1.14 indicated a higher chance of survival than an sGWR < 1.14 (54.5% vs. 13.6%). Follow-up magnetic resonance imaging for survivors validated the correlation of the mASPECTS < 15 with severe brain damage. Thus, low mASPECTS scores were associated with unfavorable neurological outcomes on the Pediatric Cerebral Performance Category scale. A quantitative analysis of early head CT findings might provide clues for predicting survival of pediatric CA.

Physical Restraints in Critically Ill Children: A Multicenter Longitudinal Point Prevalence Study.

OBJECTIVES: We elucidate to investigate the prevalence of and factors associated with the use of physical restraints among critically ill or injured children in PICUs. DESIGN: This was a multicenter, longitudinal point prevalence study. SETTING: We included 26 PICUs in Japan. PATIENTS: Included children were 1 month to 10 years old. We screened all admitted patients in the PICUs on three study dates (in March, June, and September 2019). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We collected prevalence and demographic characteristics of critically ill or injured children with physical restraints, as well as details of physical restraints, including indications and treatments provided. A total of 398 children were screened in the participating PICUs on the three data collection dates. The prevalence of children with physical restraints was 53% (211/398). Wrist restraint bands were the most frequently used means (55%, 117/211) for potential contingent events. The adjusted odds of using physical restraint in patients 1-2 years old was 2.3 (95% CI, 1.3-4.0) compared with children less than 1 year old. When looking at the individual hospital effect, units without a prespecified practice policy for physical restraints management or those with more than 10 beds were more likely to use physical restraints. CONCLUSIONS: The prevalence of physical restraints in critically ill or injured children was high, and significant variation was observed among PICUs. Our study findings suggested that patient age, unit size, and practice policy of physical restraint could be associated with more frequent use of physical restraints.

Ultrasound-guided double central venous access for azygos vein via the ninth and tenth intercostal veins.

Some patients with intestinal failure, who are dependent on total parenteral nutrition for long periods, suffer from a lack of suitable conventional venous access points, including axillary, external jugular, internal jugular, subclavian, saphenous, and the brachio-cephalic and femoral veins, due to their occlusion. Furthermore, extensive central venous stenosis and/or thrombosis of the superior and inferior vena cava may preclude further catheterization, so uncommon routes must be used, which can be challenging. In such patients, the azygos vein via the intercostal vein is a viable candidate. Thoracotomy-assisted, thoracoscopy-assisted, and cut-down procedures are currently suggested such access. We found that ultrasound-guided percutaneous puncture method was a safe and minimally invasive approach and successfully placed two central venous lines in preparation for small bowel transplantation via two different intercostal veins (ninth and tenth). Although the lung was actually located just below the target veins, an ultrasound provided augmented and clear vision, which contributed to the safe performance of the procedure without the need for invasive surgical intervention, such as thoracotomy, thoracoscopy, or rib resection using the cut-down technique. Furthermore, constant positive-pressure ventilation during vein puncture under general anesthesia also helps avoid venous collapse. Despite carrying a slight risk of light injury to the lung, artery, and nerve along with the vein compared to other procedures, we believe that ultrasound-guided puncture under general anesthesia is feasible as a minimally invasive method.

The Occurrence and Risk Factors of Inappropriately Deep Tip Position of Microcuff Pediatric Endotracheal Tube During PICU Stay: A Retrospective Cohort Pilot Study.

OBJECTIVES: Cuffed endotracheal tubes are being used increasingly for pediatric patients on mechanical ventilation. Appropriate placement of the tube tip for Microcuff (Kimberley-Clark, Roswell, GA) pediatric endotracheal tube is guided by the intubation depth mark on the device. However, inappropriately deep tip position is sometimes observed during PICU stay. The purpose of this study was to assess the occurrence and risk factors of inappropriately deep tip position of Microcuff pediatric endotracheal tube during PICU stay. DESIGN: A retrospective cohort study. SETTING: The PICU at the National Center for Child Health and Development, one of the largest tertiary pediatric hospitals in Japan. PATIENTS: All patients on mechanical ventilation with Microcuff pediatric endotracheal tube admitted between February 1, 2015, and July 31, 2016, were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of inappropriately deep tip position, defined as a position of the tube tip less than 5 mm above the carina on a chest radiograph. There were 179 cases (157 patients) requiring mechanical ventilation with Microcuff pediatric endotracheal tube during the study period. An inappropriately deep tip position was found in 42 cases (23.5%), including bronchial intubation in 13 cases (7.3%). In multivariate analysis, height in cm (odds ratio, 0.93; p < 0.001), history of abdominal disease or previous abdominal surgery (odds ratio, 4.38; p = 0.004), and oversized endotracheal tube (odds ratio, 2.93; p = 0.042) were found to be independent risk factors. CONCLUSIONS: The occurrence of inappropriately deep tip position of Microcuff pediatric endotracheal tube during PICU stay was 23.5%. The possibility of an inappropriately deep tip position should be considered whenever patients with the above risk factors, a history of abdominal disease or previous abdominal surgery, and small children are treated or when oversized endotracheal tubes are used.

Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion.

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD.

Emergent transcatheter arterial embolization for norovirus-associated life-threatening ulcer bleeding to achieve successful hemostasis in 2-year-old boy.

Case: We report a 2-year-old boy with duodenal ulcer with active bleeding that occurred as a result of norovirus gastroenteritis. On admission, the patient presented with shock accompanied with vomiting and melena. Abdominal contrast enhanced computed tomography scan showed signs of duodenal bleeding. Outcome: He was successfully treated with emergent transcatheter arterial embolization. After the treatment, endoscopic examination revealed duodenal ulcer and the stool norovirus antigen test was found to be positive. The patient recovered completely without any sequelae. Conclusion: Life-threatening duodenal ulcer bleeding in children can be caused by viral gastroenteritis. When endoscopic therapy is unsuccessful or difficult, in cases of small children, angiographic intervention can be a safe alternative treatment option of gastrointestinal bleeding.