Cystic Fibrosis Treatment Options Discrepancy Globally

Cystic fibrosis, or rather known as CF, is a common monogenic disease caused by genetic mutation on CFTR on chromosome 7. Progressive obstructive pulmonary disease, sinusitis, exocrine pancreatic insufficiency leading to malabsorption and malnutrition, liver and pancreatic dysfunction, and male infertility are all characteristics of the disease. Persistent pulmonary infections are caused by a lack of CFTR or its decreased function, leading to bronchiectasis and progressive lung destruction. Despite the fact that CF patients' lives are shortening, early diagnosis has helped improve patients' life span to a median age of around 50 years, including newborn screening, mild form identification, and a proactive therapy approach. Pancreatic enzyme replacement, respiratory physiotherapy, mucolytics, and strong antibiotic therapy are among treatments for CF. For the majority of people with severe symptoms, a lung or liver transplant is necessary. The CFTR protein is affected by a large number of mutations, each of which have diverse effects. Despite advances in our understanding of CFTR function and contemporary therapy, most of our knowledge of cystic fibrosis remains unclear. With the recent addition of mutation-specific treatments, future advances in health and quality of life for people with CF are likely to improve. The focus of research is on novel medications that restore CFTR function, some of which are now accessible and have a positive therapeutic impact, while others are showing promising preliminary results.

Substantiation of Using Pimecrolimus 1% Cream in Proactive Therapy of Children with Atopic Dermatitis

Atopic dermatitis (AtD) is multifactorial inflammatory skin disease with high prevalence in pediatric population. It is crucial to implement long-term maintenance therapy to prevent AtD exacerbations according to current clinical guidelines and expert reports. The article summarizes the results of the major studies on using pimecrolimus 1% cream. Its efficacy and safety in long-term proactive therapy of children with AtD are presented.

Effect of Coptischinensis, Glycyrrhiza uralensis, and Fermented Glycine max Extract as Proactive Therapy for Atopic Dermatitis

The aim of this study was to investigate the effect of the Coptis chinensis, Glycyrrhiza uralensis, and fermented Glycine max (3Hb) extract on lipid barrier recovery and the alleviation of atopic dermatitis (AD). The 3Hb extract was administered to lipid barrier-eliminated mice (3HbT) for 5 days. Subsequently, the effect of the 3Hb extract on general skin features and the regulation of filaggrin, inflammatory response, Th2 differentiation, and the skin micro-environment for defense, was evaluated. In the 3HbT, filaggrin was effectively recovered. The clinical skin score was significantly lower in the 3HbT compared with control groups. In addition, significant decreases in pH and TEWL as well as in the levels of kallikrein 7, PAR-2, TSLP, IL-4, Fc ε receptor, and phosphate-NF-κB p65 were observed in the 3HbT, compared with the other control groups. Further, compared with control groups, the 3HbT showed a significant increase in those of claudin, cathelicidin, TLR, and NHE-1. Our results indicated that the 3Hb extract effectively recovered filaggrin. Through the recovery of filaggrin, inflammation and the Th2 differentiation process can be regulated, and microenvironments for defense can be recovered. Therefore, we confirmed the potential of the 3Hb extract for use in the proactive therapy of AD.

A novel PillCam Crohn’s capsule score (Eliakim score) for quantification of mucosal inflammation in Crohn’s disease

Introduction Capsule endoscopy is an important modality for monitoring of Crohn’s disease. Recently, a novel panenteric capsule, PillCam Crohn’s (Medtronic, USA), was approved for use. No quantitative index of inflammation for this method is currently available. This sub-study of a prospective randomized controlled Comprehensive individUalized pRoactive ThErapy of Crohn’s Disease trial (CURE-CD) which aimed to compare the correlation and reliability of the novel PillCam Crohn’s score with the existing small bowel capsule Lewis inflammatory score. Methods The study cohort included Crohn’s disease patients in remission who were evaluated with PillCam Crohn’s. Each result was independently reviewed by two experienced readers. Inflammation was scored in all studies using Lewis inflammatory score and PillCam Crohn’s score (comprised of a sum of scores for most common and most severe lesions multiplied by percentage of segmental involvement + stricture score). Results Fifty-four PillCam Crohn’s studies from 41 patients were included. The median Lewis inflammatory score was 225 for both readers. The median PillCam Crohn’s score was six (0–14) and four (3–15) for readers 1 and 2, respectively. There was a high inter-rater reliability coefficient between the two readers for Lewis inflammatory and PillCam Crohn’s score (0.9, p < 0.0001 for both). The correlation between PillCam Crohn’s score and fecal calprotectin was stronger than for Lewis inflammatory score ( r = 0.32 and 0.54 respectively, p = 0.001 for both). Conclusions The novel panenteric capsule score correlates well with the Lewis inflammatory score, has excellent reliability, and may be potentially more accurate in estimation of the panenteric inflammatory burden.

Computational design of treatment strategies for proactive therapy on atopic dermatitis using optimal control theory

Atopic dermatitis (AD) is a common chronic skin disease characterized by recurrent skin inflammation and a weak skin barrier, and is known to be a precursor to other allergic diseases such as asthma. AD affects up to 25% of children worldwide and the incidence continues to rise. There is still uncertainty about the optimal treatment strategy in terms of choice of treatment, potency, duration and frequency. This study aims to develop a computational method to design optimal treatment strategies for the clinically recommended ‘proactive therapy’ for AD. Proactive therapy aims to prevent recurrent flares once the disease has been brought under initial control. Typically, this is done by using an anti-inflammatory treatment such as a potent topical corticosteroid intensively for a few weeks to ‘get control’, followed by intermittent weekly treatment to suppress subclinical inflammation to ‘keep control’. Using a hybrid mathematical model of AD pathogenesis that we recently proposed, we computationally derived the optimal treatment strategies for individual virtual patient cohorts, by recursively solving optimal control problems using a differential evolution algorithm. Our simulation results suggest that such an approach can inform the design of optimal individualized treatment schedules that include application of topical corticosteroids and emollients, based on the disease status of patients observed on their weekly hospital visits. We demonstrate the potential and the gaps of our approach to be applied to clinical settings. This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’.