Progress of TNF-α and TNF-α blockade treatment in asthma

Asthma is a chronic inflammatory disease of the airways, pathogenesis is complex, variety of inflammatory cells and cytokines involved in the airway allergic diseases. Tumor necrosis factor-alpha(TNF-α)plays a role in the pathogenesis of asthma as an integral part of inflammatory mediators. Suffering from asthma,respiratory epithelial cells, vascular endothelial cells may release TNF-α which may cause airway hyperreactivity and the partial inflammation, and play a role in airway remodeling. The studies show that anti-TNF-α therapy has certain therapeutic action to airway remodeling in asthma patient and severe asthma, it can decline the level of TNF-α in the blood and the respiratory, reduce airway inflammation, provide new ideas and methods for the treatment of asthma.     

Investigating the European perspective of neonatal point-of-care echocardiography in the neonatal intensive care unit—a pilot study

Point-of-care functional neonatal echocardiography (fnECHO) is increasingly used to assess haemodynamic status or patency of the ductus arteriosus (PDA). In Australasia, 90 % of neonatal intensive care units (NICUs) practice point-of-care fnECHO. The Australian Society of Ultrasound Medicine offers a training certificate for fnECHO. In Europe, the use and indications of fnECHO and the extent of point-of-care fnECHO training and accreditation are unknown. We aimed to assess utilisation and training of fnECHO in Europe. For this, we conducted an email survey of 45 randomly chosen tertiary NICUs in 17 European countries. The recall rate was 89 % (n?=?40). Neonatologists with skills in fnECHO worked in 29 NICUs (74 %), but paediatric cardiologists would routinely perform most fnECHOs. Twenty-four-hour echocardiography service was available in 31 NICUs (78 %). Indications for fnECHO included assessment of haemodynamic volume status (53 %), presence or absence of pulmonary hypertension of the neonate (55 %), indication for and effect of volume replacement therapy (58 %), PDA assessment and monitoring of PDA treatment (80 %). Teaching of fnECHO was offered to trainees in 22 NICUs (55 %). Teaching of fnECHO was provided by paediatric cardiologists (55 %) or by neonatologists (45 %). Only six (15 %) national colleges accredited fnECHO teaching courses. Conclusion: fnECHO is widely practiced by neonatologists across Europe for a broad range of clinical questions. However, there is a lack of formal training and accreditation of fnECHO skills. This could be addressed by designing a dedicated European fnECHO training programme and by agreeing on a common European certificate of fnECHO.     

Immune response to gangliosides in a case of Guillain-Barré syndrome after varicella

An 8 year old girl was admitted to hospital with the typical clinical features of Guillain-Barré syndrome (GBS) after recovering from varicella. Onset of the disease was just two weeks after the onset of varicella in her young sister. Examination of cerebrospinal fluid and nerve conduction studies showed typical findings of GBS. Although serum from both the patient and sister were analysed for autoantibodies to gangliosides and myelin P0 protein, IgM anti-GM1 antibody and anti-GD1b antibody were only detected in the patient. HLA DR haplotypes were quite different between the two subjects. This suggests that these autoantibodies may play an important role in the pathogenesis of GBS after varicella zoster virus infection.     

Life-threatening disseminated tuberculosis as a complication of TNF-α blockade in an adolescent

Life-threatening disseminated tuberculosis developed in a 17-year-old girl who was treated with the TNF-α blocker adalimumab for refractory SAPHO syndrome. The patient presented to the emergency department with dyspnea and somnolence and within 2 h developed the clinical picture of a septic shock. In addition to this unusual presentation, she showed a complicated course with increasing cerebral granuloma formation in spite of adequate antimycobacterial treatment. Immune reconstitution after discontinuation of TNF blockade may contribute to this “paradoxical reaction.” Possible implications for screening, diagnosis, and treatment of tuberculosis in children and adolescents receiving anti-TNF treatment are discussed.     

Metabolic and functional response of neonatal pig hearts to the development of ischemic contracture: is recovery possible?

The potential for functional and metabolic recovery in neonatal hearts after the development of ischemic contracture remains controversial and undefined. This study documents post-ischemic recovery of metabolism and function in the in vivo neonatal heart after the development of onset and peak ischemic contracture. In piglets on cardiopulmonary bypass, hearts were reperfused after the development of either onset (TICo) or peak (TICp) ischemic contracture. Systolic (developed and systolic function, contractility) and diastolic (diastolic function, relaxation) performance was assessed throughout reperfusion. Biopsies were obtained at end-ischemia or end-reperfusion to assess metabolism. By end-ischemia, the metabolic profiles of both TICo and TICp hearts confirmed energy-store depletion and purine degradation that was quantitatively greater in TICp hearts. Hearts reperfused at TICo had consistent moderate impairment of developed function, contractility, diastolic function, and relaxation, whereas hearts reperfused at TICp had much more profound functional impairment. Diastolic function showed the worst functional recovery. In contrast, systolic function was not significantly altered in either study group and, thus, did not reflect the actual extent of injury. In addition, TICo hearts either did not further deplete or partially regenerated energy stores during reperfusion, whereas TICp hearts had further energy-store depletion and lactate accumulation. In summary, neonatal hearts reperfused after TICo maintained or partially restored energy stores and had significant but incomplete functional recovery. In contrast, further metabolic deterioration and profound functional impairment occurred with reperfusion after TICp, potentially indicating ongoing mitochondrial injury and compromised oxidative phosphorylation.     

Can methadone concentrations predict the severity of withdrawal in infants at risk of neonatal abstinence syndrome?

AIM: To assess the usefulness of cord and serum methadone concentrations at 2 days of age in predicting the severity of neonatal abstinence syndrome (NAS) in infants whose mothers received methadone during pregnancy. METHODS: After informed consent, infants were enrolled if they were delivered at 35 weeks gestation or greater. Relevant information was collected from maternal notes. A sample of cord blood was taken at delivery, with a follow up sample at 48 hours of age. The samples were analysed in batches, and the results were unavailable to the attending clinical staff. Infants were treated for NAS on clinical grounds according to a standardised scoring system. RESULTS: Twenty five of 36 eligible infants over the 21 month period of the study were enrolled. Of these, 12 required treatment for NAS. Maternal methadone dose did not predict the need for treatment. However, infants who required treatment had significantly lower methadone concentrations in cord blood than the group who did not receive treatment (31 v 88 ng/ml respectively; p = 0.029). Paired blood samples for methadone concentrations were available for 17 infants. All but one of the 12 infants who required treatment had undetectable concentrations of methadone in the postnatal sample, whereas the median postnatal methadone concentration in untreated infants was 23 ng/ml (p = 0.002). CONCLUSIONS: Methadone concentrations taken from cord blood may identify infants at greater risk of neonatal withdrawal and therefore requiring treatment.     

Immune response to gangliosides in a case of Guillain-Barré syndrome after varicella.

An 8 year old girl was admitted to hospital with the typical clinical features of Guillain-Barré syndrome (GBS) after recovering from varicella. Onset of the disease was just two weeks after the onset of varicella in her young sister. Examination of cerebrospinal fluid and nerve conduction studies showed typical findings of GBS. Although serum from both the patient and sister were analysed for autoantibodies to gangliosides and myelin P0 protein, IgM anti-GM1 antibody and anti-GD1b antibody were only detected in the patient. HLA DR haplotypes were quite different between the two subjects. This suggests that these autoantibodies may play an important role in the pathogenesis of GBS after varicella zoster virus infection.     

Does smoking in pregnancy modify the impact of antenatal steroids on neonatal respiratory distress syndrome? Results of the Epipage study

OBJECTIVES: To assess the relation between cigarette smoking during pregnancy and neonatal respiratory distress syndrome (RDS) in very preterm birth, and to analyse the differential effect of antenatal steroids on RDS among smokers and non-smokers. DESIGN: A population based cohort study (the French Epipage study). SETTING: Regionally defined births in France. METHODS: A total of 858 very preterm liveborn singletons (27-32 completed weeks of gestation) of the French Epipage study were included in this analysis. The odds ratio for RDS in relation to smoking in pregnancy was estimated using a logistic regression to control for gestational age. The odds ratio for RDS in relation to antenatal steroids was estimated taking into account an interaction between antenatal steroids and cigarette smoking, using multiple logistic regression to control for gestational age, birthweight ratio, main causes of preterm birth, mode of delivery, and sex. RESULTS: The odds ratio for RDS in relation to smoking in pregnancy adjusted for gestational age (aOR) was 0.59 (95% confidence interval (CI) 0.44 to 0.79). The aOR for RDS in relation to antenatal steroids was 0.31 (95% CI 0.19 to 0.49) in babies born to non-smokers and 0.63 (95% CI 0.38 to 1.05) in those born to smokers; the difference was significant (p = 0.04). CONCLUSIONS: Cigarette smoking during pregnancy is associated with a decrease in the risk of RDS in very preterm babies. Although antenatal steroids reduce the risk of RDS in babies born to both smokers and non-smokers, the reduction is smaller in those born to smokers.     

Sweet’s syndrome in a neonate with non-B54 types of human leukocyte antigen

Background

Sweet??s syndrome (acute febrile neutrophilic dermatosis) is characterized by fever, polymorphonuclear leukocytosis of blood, painful plaques on the limbs, face and neck, and histologically a dense dermal infiltration with mature neutrophils. Sweet??s syndrome is often a complication of hematologic malignant disease or drug-induced sensitivity reactions and has a significant susceptibility correlated with certain human leukocyte antigen (HLA).

Methods

A 5-week-old Japanese girl with Sweet??s syndrome confirmed by skin biopsy was successfully treated and HLA analysis was performed.

Results

The patient was one of the youngest patients reported with Sweet??s syndrome, suggesting the importance of the genetic background. Although the HLA types of the patient did not have B54, which was reported as a significant susceptibility correlation, structural analysis of the patient??s HLAs suggested a similar possible motif for the bound peptides.

Conclusion

Studies on the HLA bound peptides and HLA structural analysis for patients with Sweet??s syndrome would be valuable for understanding the molecular mechanism of the pathogenesis.     

Efficacy of volume-targeted ventilation versus high-frequency oscillatory ventilation in the treatment of neonatal respiratory distress syndrome北大核心CSCD

Objective To study the clinical efficacy of volume-targeted ventilation (VTV) versus high-frequency oscillatory ventilation (HFOV) in the treatment of neonatal respiratory distress syndrome (NRDS). Methods A retrospective cohort analysis was performed on the medical data of 140 neonates with severe NRDS who were admitted from September 2016 to February 2022, with 55 neonates in the VTV group and 85 in the HFOV group. The neonates in the VTV group received conventional mechanical ventilation and target tidal volume, and those in the HFOV group received HFOV. Arterial blood gas parameters were collected at 48 hours after admission, and related indices during hospitalization were recorded, including mortality rate, duration of invasive mechanical ventilation, duration of oxygen therapy, and the incidence rates of complications. Results Compared with the VTV group, the HFOV group had significantly lower incidence rates of grade Ⅲ-Ⅳ periventricular-intraventricular hemorrhage and neonatal necrotizing enterocolitis (P<0.05), and there were no significant differences between the two groups in the duration of invasive mechanical ventilation, the duration of oxygen therapy, mortality rate, and the incidence rates of bronchopulmonary dysplasia, hypocapnia, hypercapnia, periventricular leukomalacia, and retinopathy of prematurity (P>0.05). Conclusions HFOV has a better clinical efficacy than VTV in the treatment of NRDS. © 2022 Xiangya Hospital of CSU. All rights reserved.     

Upregulated expression of EGF and TGF-α in the proximal respiratory epithelium in the human hypoplastic lung in congenital diaphragmatic hernia

Newborn infants with congenital diaphragmatic hernia (CDH) still have a high mortality rate. Epidermal growth factor (EGF) and transforming growth factor- (TGF-) are peptide growth factors involved in the fetal lung growth and development. The EGF and TGF- have been reported to promote pulmonary branching activity and alveolar type-II pneumocyte proliferation. Epidermal growth factor and TGF- immunoreactivity and mRNA expression in the bronchial and bronchiolar epithelium is maximal during early fetal life and barely detectable in the proximal airways of neonatal lung. The purpose of this study was to determine protein and gene expression of EGF and TGF- in CDH lung in order to elucidate the potential role of these growth factors in the pathogenesis of pulmonary hypoplasia in CDH. Lung tissue specimens were obtained from archival lung tissue from 11 patients with CDH and 5 controls. Indirect immunohistochemistry was performed using ABC method with anti-EGF and anti-TGF- antibodies. In situ hybridization was performed using EGF and TGF- specific digoxigenin-labeled oligonucleotide probes. The most striking difference between hypoplastic CDH lung and control lung was the strong EGF and TGF- mRNA expression and immunoreactivity in the bronchial and bronchiolar epithelium in CDH lung. The upregulated protein and gene expression of EGF and TGF- in the proximal airways in the CDH hypoplastic lung suggests persistence of fetal stage of pulmonary airway development in CDH.     

Is thrombocytopenia suggestive of organism‐specific response in neonatal sepsis?

Background:  It is controversial whether thrombocytopenia is suggestive of one (or more) causative agents of neonatal sepsis: a low platelet count has been related in turn to Gram-positive, Gram-negative or fungal sepsis.
Methods:  A retrospective, cohort study on 514 very low-birthweight (VLBW) neonates admitted over a 9 year period to a large tertiary neonatal intensive care unit (NICU) in Italy was carried out. Through database search, data on platelet counts, sepsis, clinical course, and microbiological culture were collected and analyzed. Statistical analysis was performed to look for significant association between thrombocytopenia and sepsis caused by different (Gram-positive, Gram-negative or fungal) organisms.
Results:  Sepsis diagnosed on microbiological criteria occurred in 197 of 514 VLBW neonates (38.3%), and thrombocytopenia (at least one finding of platelet count <80 000/mm³) was detected in 34 (17.2%) of the 197 septic infants. Thrombocytopenia occurred in 10 of 51 neonates with fungal sepsis (19.6%), and in 24 of 146 with bacterial sepsis (16.4%; P  = 0.37). The difference was not significant when clustering for sepsis caused by Gram-positive (nine thrombocytopenic of 51 with Gram-positive sepsis, 17.6%; P  = 0.40) and Gram-negative organisms (15/95, 15.7%; P  = 0.22), or when considering only coagulase-negative Staphylococcus sepsis (6/37, 16.2%; P  = 0.25).
Conclusions:  In contrast with previous reports, thrombocytopenia might not be an organism-specific marker of sepsis. Caution should be maintained in relating a low platelet count to any infectious agent (or group of agents) in preterm VLBW neonates.