Respiratory function testing for guiding ventilator mode conversion in congenital diaphragmatic hernia.

INTRODUCTION: For patients with a congenital diaphragmatic hernia, conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) are used in initial ventilatory management. HFOV has recently been recommended as a rescue therapy; however, we use HFOV for initial ventilation management, with a preoperative challenge test for CMV conversion and respiratory function testing at the time of CMV conversion. We aimed to compare patient characteristics between CMV conversion- and HFOV-preferred treatment groups. METHODS: Ventilator settings and blood gases were retrospectively evaluated pre- and post-CMV conversion, and respiratory function tests for compliance of the respiratory system (Crs) and for resistance of the respiratory system (Rrs) were performed during the trial to CMV conversion. RESULTS: No differences were observed between the CMV conversion- and HFOV-preferred groups regarding gestational age, birth weight, and observed/expected lung area-to-head circumference ratios. The median Crs (ml/cmH2 O/kg) and Rrs (cmH2 Oï½¥kg/L/s) in the CMV conversion- and HFOV-preferred groups was 0.42 versus 0.53 (p = .44) and 467 versus 327 (p = .045), respectively. The pre and posttrial amount of change in blood gas levels and ventilator parameters in the CMV conversion- and HFOV-preferred groups were as follows: mean airway pressure, -2.0 versus 0 cmH2 O; partial pressure of carbon dioxide, 6.1 versus 2.9 Torr; alveolar-arterial oxygen difference, -39.5 versus -50 Torr; and oxygenation index, -1.0 versus -0.6; respectively. CONCLUSION: Respiratory function tests were useful in tailoring ventilator settings. Patients with high Rrs values responded better to CMV conversion.

Interleukin-33 and Soluble ST2 Levels in Infants with Hypoxic-Ischemic Encephalopathy.

INTRODUCTION: Interleukin (IL)-33 and its receptor ST2L play key roles in the IL-33/ST2 signaling pathway. Soluble ST2 (sST2) inhibits the proper function of IL-33. sST2 levels are increased in patients with several neurological diseases, but in infants with hypoxic-ischemic encephalopathy (HIE), IL-33 and sST2 levels have not been studied. This study aimed to investigate whether serum levels of IL-33 and sST2 are useful as biomarkers of HIE severity and prognostic factors for infants with HIE. METHODS: Twenty-three infants with HIE and 16 controls (gestational age ≥36 weeks and ≥1,800 g birth weight) were enrolled in this study. Serum levels of IL-33 and sST2 were measured at <6 h, 1-2, 3, and 7 days of age. Hydrogen-1 magnetic resonance spectroscopy was performed, and ratios of peak integrals of lactate/N-acetylaspartate (Lac/NAA) were calculated as objective indicators of brain damage. RESULTS: In the moderate and severe HIE, serum sST2 concentrations were increased and there was a good correlation between serum sST2 and HIE severity on days 1-2, whereas no variation was observed in serum IL-33. Serum sST2 levels were positively correlated with Lac/NAA ratios (Kendall's rank correlation coefficient = 0.527, p = 0.024), and both sST2 and Lac/NAA ratios were significantly higher in HIE infants with neurological impairment (p = 0.020 and <0.001, respectively). CONCLUSIONS: sST2 may be a useful predictor of severity and later neurological outcomes in infants with HIE. Further investigation is required to elucidate the relationship between the IL-33/ST2 axis and HIE.

Right to left ventricular volume ratio is associated with mortality in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality. We performed this study to test the hypothesis that left ventricular (LV) and right ventricular (RV) volumes assessed by three-dimensional echocardiography may be associated with mortality in CDH. METHODS: This study was a single-center retrospective cohort study involving 35 infants with CDH. RV and LV end-diastolic volume (RVEDV and LVEDV, respectively) were measured by three-dimensional echocardiography and were corrected by birth body weight (BBW) on day 1. RVEDV/BBW, LVEDV/BBW, and LVEDV/RVEDV were compared between CDH survivors and non-survivors. Receiver-operating characteristic curve analysis was performed to assess the predictive ability for mortality of the echocardiographic parameters. RESULTS: Comparing CDH non-survivors (n = 6) with survivors (n = 29), respectively, RVEDV/BBW was significantly larger (2.54 ± 0.33 vs 1.86 ± 0.35 ml/kg; P < 0.01), LVEDV/BBW was significantly smaller (0.86 ± 0.21 vs 1.22 ± 0.33 ml/kg; P < 0.001), and LVEDV/RVEDV was significantly lower (0.34 ± 0.06 vs 0.66 ± 0.18; P < 0.001). The area under the curve for LVEDV/RVEDV was the largest (0.98). CONCLUSIONS: Three-dimensional echocardiographic volume imbalance between the RV and LV was remarkable in CDH non-survivors. The LVEDV/RVEDV ratio may be associated with mortality in CDH. IMPACT: Mortality with congenital diaphragmatic hernia (CDH) is high, and evaluating left and right ventricular structures and functions may be helpful in assessing the prognosis. Three-dimensional (3D) echocardiography indicated that the left ventricular end-diastolic volume/right ventricular end-diastolic volume ratio within 24 h after birth was associated with mortality in CDH infants. The usefulness of this ratio should be validated in prospective multicenter studies involving larger numbers of patients.

Novel compound heterozygous mutations in the PLEC gene in a neonate with epidermolysis bullosa simplex with pyloric atresia.

Epidermolysis bullosa (EB) is a heterogeneous group of inherited disorders characterized by the blistering of the skin and mucous membranes. Although the molecular basis of EB has been significantly elucidated, the precise phenotypes of the lethal types of EB have not been completely characterized. Herein, we report a severe case of EB with pyloric atresia (PA). The patient was a Japanese boy who not only had skin lesions but also various complications such as PA, dysphagia, hypotonia, infectious keratitis with corneal ulcer, obstructive uropathy and protein-losing enteropathy. Genetic analysis led to the identification of two novel compound heterozygous mutations in the last exon of the plectin (PLEC) gene. Based on this finding, EB simplex with PA was diagnosed. Immunostaining with anti-plectin antibodies revealed truncated plectin proteins lacking the C-terminus in the patient's skin. We also conducted a prenatal diagnosis in subsequent pregnancy. Our report further highlights the crucial role of plectin in many organs and provides valuable information regarding the phenotypes resulting from mutations in the PLEC gene.

Histological characteristics of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in asthmatic murine model during A(H1N1)pdm09 infection.

Pandemic influenza virus A(H1N1)pdm09 infection occurred in healthy children and young adults, but asthmatic patients presented more rapid progression of respiratory distress and plastic bronchitis. To investigate the pathogenesis of worsening respiratory symptoms after A(H1N1)pdm09 infection, we focused on matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1). MMP-9 and TIMP-1 levels in bronchoalveolar lavage fluid and serum from mice with and without asthma were evaluated after A(H1N1)pdm09 or seasonal A(H1N1) infection. MMP-9 levels were more elevated in Asthma/A(H1N1)pdm09-infected mice than in non-Asthma/A(H1N1)pdm09-infected mice on both 3 and 7 days post-infection. Immunohistochemical findings in this pneumonia model showed that MMP-9 and TIMP-1 positive cells were observed in blood vessels and bronchus of lung tissue in severe pathological findings of pneumonia with asthma. Microscopically, shedding cells and secretions were conspicuous in the trachea on days 3 and 7 post-infection, in the A(H1N1)pdm09-infected mice with asthma. Our results suggest that MMP-9 and TIMP-1 expressions are related to severe pneumonia in the A(H1N1)pdm09 infection with asthma, leading to cause epithelial cell shedding.

Successful Treatment of Saddle Pulmonary Thromboembolism in 23-Week Preterm Infant.

Saddle pulmonary thromboembolism (PTE) is defined as a thromboembolism straddling the bifurcation of the main pulmonary artery trunk and it is rarely seen in extremely low birth weight infants (ELBWI). Saddle PTE is a critical disease that requires urgent treatment. However, the treatment guidelines for ELBWI are not established. We present the case of a 1-day-old preterm infant (gestational age 23 weeks) who showed sudden desaturation and pulmonary hypertension due to saddle PTE. A thrombus was observed in the bifurcation of the pulmonary artery. The blood flow to the pulmonary artery on the left side was interrupted, and the right side showed severe stenosis. Since the patient was an ELBWI in the acute phase, we decided to use recombinant tissue plasminogen activator (rt-PA) and administered a maintenance dose (0.08 mg/kg/hour), instead of the loading dose. After using rt-PA, the thrombus dissolved in 8 hours without adverse events. This case suggests that starting with a maintenance dose of rt-PA may be an effective treatment option for saddle PTE in ELBWI in the acute phase under the high risk of bleeding.

Pulmonary Hypertension Following Increased Dosing of Diazoxide in an Infant.

Diazoxide, a drug used to treat hyperinsulinemic hypoglycemia (HH), is associated with pulmonary hypertension (PH), as reported by the US Food and Drug Administration. However, no report has detailed the association between diazoxide dose and PH development. We report a case of an infant with HH, subsequently complicated by diazoxide-induced PH. When diazoxide was introduced, PH did not appear initially, but it developed during increased dosing. We monitored PH via regular echocardiography examinations. PH gradually improved with tapering of the diazoxide dose and disappeared after drug discontinuation. Our case suggests a diazoxide dose threshold might induce PH. Therefore, close echocardiography examinations should accompany diazoxide treatment.

Using airway resistance measurement to determine when to switch ventilator modes in congenital diaphragmatic hernia: a case report.

BACKGROUND: Congenital diaphragmatic hernia is a deficiency of the fetal diaphragm resulting in herniation of the abdominal viscera into the thoracic cavity. The best method of respiratory management of congenital diaphragmatic hernia is unclear, but high frequency oscillatory ventilation is often used as the initial ventilator mode for severe congenital diaphragmatic hernia. When it becomes impossible to maintain the pre-ductal saturations, the timing of successful switching of the ventilation mode from high frequency oscillatory ventilation to conventional mechanical ventilation remains unclear. Herein, we reported two cases in which airway resistance measurements based on pulmonary function tests were used for making the decision to switch the ventilator mode from high frequency oscillatory ventilation to conventional mechanical ventilation in patients with left isolated congenital diaphragmatic hernia. CASE PRESENTATION: Two 0-day-old infants with congenital diaphragmatic hernia were admitted to our hospital. In both patients, high frequency oscillatory ventilation was started initially, and the levels of saturation gradually rose within a few hours after birth. After 24 h of high frequency oscillatory ventilation, the level of saturation decreased, and the dissociation of pre-ductal and post-ductal saturation re-occurred. The respiratory-system resistance was 515 and 403 cmH2O·kg/L/s, respectively. Because the respiratory-system resistance was elevated, we decided to change the ventilator mode from high frequency oscillatory ventilation to conventional mechanical ventilation. After switching to conventional mechanical ventilation, the patients' heart rate and saturation increased immediately. CONCLUSIONS: In patients with congenital diaphragmatic hernia, resistance levels of > 400 cmH2O·kg/L/s may indicate high airway resistance and suggest greater alveolar vibration attenuation. When respiratory-system resistance reaches over 400 cmH2O·kg/L/s, it may be an optimal time for switching from high frequency oscillatory ventilation to conventional mechanical ventilation.

A Sporadic Neonatal Case of Epidermolysis Bullosa Simplex Generalized Intermediate with KRT5 and KRT14 Gene Mutations.

Background Epidermolysis bullosa simplex (EBS) is a rare genodermatosis resulting from multiple gene mutations, including KRT5 and KRT14. The clinical expression of the mechanobullous skin fragility disease has not been fully explained by the genotype. Case Description An 11-day-old Japanese newborn infant was hospitalized because of herpetiform skin blistering on the feet, which expanded systemically after birth. There was no evidence of virus infection. The biopsied skin lesion showed a blister on the lamina densa without keratin clumps, indicating a diagnosis of EBS-generalized intermediate. We punctured the blisters to remove the contents daily, which led to no exacerbation or infection. The genetic study determined that the patient carried double substitutions of KRT5 c.1424A > G (p.E475G) and KRT14 c.1237G > A (p.A413T). The asymptomatic mother and sister carried the KRT14 substitution, but the healthy father had no substitution of the KRT gene. Conclusion This is the first report of EBS-generalized intermediate in a newborn with de novo KRT5 gene mutation and KRT14 gene polymorphism, and no familial history of epidermolysis. Neonatal blistering due to EBS requires optimal skin management after excluding infectious and immunobullous diseases.

Cat-scratch disease with severe pleuritis in a 6-year-old girl.

We present the case of a 6-year-old girl with cat-scratch disease (CSD), who developed severe pleuritis without lymphadenitis. Bartonella henselae DNA was detected on real-time polymerase chain reaction (PCR) analysis of whole blood. This is the first report of CSD diagnosed on real-time PCR using whole blood.