Severe asthma in children—a review of definitions,epidemiology, and treatment options in 2019

Severe asthma is a relatively uncommon condition in children but one which causes morbidity, occasionally mortality, and is a challenging condition to manage. There are several definitions of severe asthma, which have a common theme of poor control despite high dose inhaled corticosteroid treatment. Depending on the definition chosen, the prevalence of severe childhood asthma may be up to 5% within populations with asthma. Collectively, there is some evidence that the treatments used in severe asthma are beneficial, but a solid evidence‐base is lacking for many treatments and some treatments have recognized side effects. Evidence supporting the use of maintenance oral prednisolone and intramuscular triamcinolone is weak. Response to systemic corticosteroids is heterogeneous and recognizing phenotypes or endotypes may identify those most likely to gain maximal benefit from treatment. For children aged 6 to 11 years, the anti‐IgE biologic omalizumab is effective and anti‐IL‐5 agent (mepolizumab) has recently been licenced in Europe (but not the US). Biologics, which are licenced for >11 year olds include omalizumab, mepolizumab, benralizumab, reslizumab, and dupilumab. There is plenty that the clinician can offer to the child and adolescent with severe asthma in 2019, including nontherapeutic and therapeutic interventions. To manage severe asthma, practitioners from broad specialities must establish and maintain a close therapeutic relationship with patients. Looking beyond 2019, more treatment options will emerge for severe childhood asthma, and clinical teams will need to continue weighing up benefits and harms.     

Hepatitis C virus: The role of molecular mimicry in response to interferon treatment

Chronic hepatitis C virus (HCV) infection is one of the major causes of chronic liver disease worldwide. In order for HCV to persist, the virus must escape immune recognition or inhibit the host immune response. The NS5A protein contains the interferon sensitivity‐determining region (ISDR) and is able to repress dsRNA‐dependent protein kinase (PKR) thus influencing the response to interferon (IFN) therapy. Patients who respond to IFN therapy have stronger antibody reactivity against the NS5A compared to IFN non‐responders. Therefore, given the possible role for the ISDR in IFN resistance and differential antibody reactivity, it is possible that variation in ISDR may be involved in viral immune escape and development of persistent HCV infection employing aspects of host mimicry. In this study, pre‐treatment samples obtained from HCV infected patients were used to investigate the effect of different NS5A ISDR variants on the IFN antiviral response and their involvement in immune evasion. The NS5A was identified as a homologue of the variable region of immunoglobulins (Ig). The IFN resistant genotypes had higher levels of similarity to Ig compared to IFN sensitive genotypes. Expression of NS5A‐6003 (HCV genotype 1b) and NS5A‐6074 (HCV genotype 2a) was able to rescue vesicular stomatitis virus (VSV) from IFN inhibition and restore luciferase activity. A correlation between Ig‐like NS5A structure and also antibody response with the outcome of IFN treatment was observed. J. Med. Virol. 84:1571–1585, 2012. © 2012 Wiley Periodicals, Inc.     

Dementia prevalence,care arrangement,and access to care in Lebanon: A pilot study

Introduction

In North Africa and the Middle East, studies about dementia prevalence are scarce. A pilot study was conducted in Lebanon to assess dementia prevalence, using the Arabic-validated 10/66 Dementia Research Group (DRG) diagnostic assessment for case ascertainment. The study also examined care arrangement and access to care.

Strategies in the management of post-burn breast deformities

Background

Burn injuries to the chest area may end up with severe breast deformity and asymmetry. They are frequently complex and unique to each case, affecting parenchymal development, breast implantation on chest wall, nipple areola complex position, infra-mammary fold definition, and skin envelope. Furthermore, contractures affecting adjacent territories may occur and add to the deformity. Surgical correction should address all the deformity components. Thus, a structured reconstructive plan that recruits different mammaplasty techniques and deals with adjacent territories is needed. This work presents different strategies used in treating severe post-burn breast deformities. Elaborate analyses of the deformities, surgical techniques, and outcomes are presented and a structured reconstructive plan is proposed.

Methods

Sixteen deformed breasts in 11 patients (mean age, 22 years) were managed. The techniques used included a variety of mastopexy techniques, prosthesis-based endoscopic breast reconstruction, and autologous breast augmentation with fat grafting or local flaps in some hypoplastic cases. Ancillary procedures to the neck, axilla, and abdomen were carried out to release the breast when tethered by their contractures.

Results

Considerable improvement and reasonable symmetry were achieved in most cases. All patients were satisfied with the results, tolerated the need for multiple procedures, and accepted residual minor asymmetries.

Conclusions

A post-burn breast deformity has a complex nature that may be addressed on multiple stages with different techniques of mastopexy, augmentation, and reconstruction. Ancillary procedures to a contracted adjacent territory may be needed to release the breast if tethered. Adopting a structured reconstructive plan may help obtain reproducible constant results. Level of Evidence: Level IV, therapeutic study.     

Relationships between the electroretinogram a-wave,b-wave and oscillatory potentials and their application to clinical diagnosis

The electroretinogram is the electrical response of the retina to a light stimulus. The amplitude and temporal pattern of its components, the a-wave, the b-wave and the oscillatory potentials, depend on the functional integrity of the retina, on the intensity of test flash reaching the retina and on the ambient illumination. The latter contributions to the normal variability in the electroretinogram can be circumvented by constructing the relationships between the different electroretinogram waves. The electroretinogram responses were recorded from 18 dark-adapted subjects with normal vision. The slope of the a-wave and the amplitude of the b-waves were measured in the time domain. The oscillatory potentials were isolated by a digital filter and were transformed to the frequency domain for quantitative measurement. The relationship between each pair of variables could be fitted by linear segments. Our findings suggest that this mode of electroretinogram analysis can be useful in localizing the site of action of retinal disorders and that the relationship between the a-wave slope and the power density of the oscillatory potentials is a useful index for identifying disorders of the inner retina.     

Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells

BACKGROUND: It was recently shown that glucose challenge leads to increased generation of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNs) and mononuclear cells (MNCs). OBJECTIVE: To further elucidate the relation between nutrition and ROS generation, we investigated the effect of lipid and protein challenges on ROS generation by leukocytes. DESIGN: After having fasted overnight, one group of healthy subjects consumed a carbohydrate- and protein-free cream preparation (1257 kJ) and another group of healthy subjects consumed an equienergetic pure preparation of casein. Sequential blood samples were obtained after the intake of cream and casein. ROS were measured by chemiluminescence after stimulation by N-formyl-methionyl-leucinyl-phenylalanine. Lipid peroxidation was measured as thiobarbituric acid-reactive substances (TBARS) and alpha-tocopherol was measured by HPLC. RESULTS: ROS generation by MNCs and PMNs increased significantly 1, 2, and 3 h after cream intake and 1 h after protein intake. Cholesterol concentrations did not change significantly, whereas triacylglycerol concentrations increased significantly 2 h after cream intake. Total TBARS concentrations increased 1 h after cream intake and remained elevated 3 h after intake, but the increase was not significant when corrected for changes in triacylglycerol. After casein intake, total cholesterol, triacylglycerol, and TBARS concentrations did not change significantly. alpha-Tocopherol concentrations did not change significantly after either cream or casein intake. CONCLUSIONS: Both fat and protein intakes stimulate ROS generation. The increase in ROS generation lasted 3 h after cream intake and 1 h after protein intake. Cream intake also caused a significant and prolonged increase in lipid peroxidation. These data are important because increased ROS generation and lipid peroxidation are key events in atherogenesis.     

Is a fast necessary when initiating the ketogenic diet?

The purpose of this study was to determine time of onset of ketosis and efficacy when the classic ketogenic diet is initiated at full calories without a prior fast in children with epilepsy. A retrospective hospital and neurology clinic chart review was done of all 14 children commenced on the classic ketogenic diet at full calories without a prior fast between January 1, 1997, and May 31, 2001, to determine time to ketosis, time to good ketosis (urine ketones > or =80 mg/dL), and success of the ketogenic diet. Median age at diet initiation was 63 months (25th-75th percentile 47-149 months). There were 7 girls and 7 boys. Four had symptomatic generalized epilepsy, whereas the remainder had partial seizures +/- secondary generalization. Twelve of 14 children suffered seizures on a daily basis prior to the ketogenic diet. Six were commenced on the diet as outpatients, whereas 8 were admitted to hospital. No patients were fasted. All admitted patients were started on a 1:1 ketogenic ratio at full calories for the first 24 hours and advanced to a 3:1 or 4:1 ratio over 3 to 4 days, while outpatients were started on a 1:1 or 2:1 ratio and similarly advanced. Thirteen of 14 patients were successfully started on the diet, with 1 developing vomiting and food refusal during the initial hospitalization but after ketosis was established. One child was lost to follow-up after initial hospital discharge. Information regarding time to ketosis was determined for all inpatients. Mean time to onset of ketosis was 33 hours (range 17 to 48) and to good ketosis, 58 hours (range 40 to 84). Five of 12 children (42%) experienced success with the ketogenic diet, and all of these had their antiepileptic medications either withdrawn (n = 3) or decreased (n = 2). The ketogenic diet can be effectively initiated without a fast in children with epilepsy. Time to ketosis and diet efficacy are similar to protocols that use a fast.