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This book provides a comprehensive overview of the past, current and forthcoming advancements in cystic fibrosis research and clinical care.

Chronic organ damage: Understanding fibrosis
Fibrosis was once considered irreversible, resulting from chronic organ damage; Ken-Ichi Kobayashi from Notre Dame Seishin University tells us why the possibility of treatment to reverse the disease is gaining attention. Organ fibrosis is a common phenomenon observed in various organ failure states resulting from disease and aging. The most common examples are renal fibrosis in chronic kidney disease, liver fibrosis in cirrhosis, lung fibrosis in idiopathic pulmonary fibrosis, and pancreatic fibrosis in chronic pancreatitis. The total number of patients with organ fibrosis in Japan is nearly 20 million, and it is no exaggeration to say that it is a 'national disease.' Until recently, fibrosis was considered to be the end result of chronic organ damage and an irreversible condition with a poor prognosis. In recent years, however, fibrosis has begun to be recognized as a reversible process, and the possibility of treatment is gaining attention. It is also becoming clear that fibrosis is caused by complex cellular and inter-organic networks rather than by specific organs, and therefore, common pathological mechanisms are thought to exist even in various types of fibrosis. However, the common pathological mechanism of fibrosis, especially fibrosis-attracting factors, is still an enigma.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause chronic pulmonary infection, particularly in individuals with preexisting inflammatory lung disease such as cystic fibrosis(CF). Pulmonary disease caused by NTM has emerged as a major threat to the health of individuals with CF but remains difficult to diagnose and problematic to treat. In response to this challenge, the US Cystic Fibrosis Foundation (CFF) and the European Cystic Fibrosis Society (ECFS) convened an expert panel of specialists to develop consensus recommendations for the screening, investigation, diagnosis and management of NTM pulmonary disease in individuals with CF. Nineteen experts were invited to participate in the recommendation development process. Population, Intervention, Comparison, Outcome (PICO) methodology and systematic literature reviews were employed to inform draft recommendations. An anonymous voting process was used by the committee to reach consensus. All committee members were asked to rate each statement on a scale of: 0, completely disagree, to 9, completely agree; with 80% or more of scores between 7 and 9 being considered 'good' agreement. Additionally, the committee solicited feedback from the CF communities in the USA and Europe and considered the feedback in the development of the final recommendation statements. Three rounds of voting were conducted to achieve 80% consensus for each recommendation statement. Through this process, we have generated a series of pragmatic, evidence-based recommendations for the screening, investigation, diagnosis and treatment of NTM infection in individuals with CF as an initial step in optimising management for this challenging condition.

Working with a group of investigators from the European Respiratory Society (ERS)/European Cystic Fibrosis Society (ECFS) task force for the "Provision of care in adults with cystic fibrosis (CF)" [1], we have previously modelled future trends in CF demography in European countries by calculating flows of patients entering and exiting CF cohorts in each country [2]. In that report, we used individual country data contained in the ECFS Patient Registry and were able to calculate demographic forecasts for several European Countries, including France [2]. These forecasts, which were based on the assumption that major demographic trends remained stable over time, suggested that a major increase in the number of CF adults was expected in western European countries by 2025 [1, 2]. In France, our forecast predicted an increase by 45.5% in the CF population between 2010 and 2025, corresponding to an increase by 18.4% in the paediatric population and an increase by 75.7% in the adult population [2].

Special Issue: Proceedings of the 14th Paris Hepatology Conference. International Conference on the Management of Liver Diseases, 8‐10 March 2021, Paris, France. ; The prevalence of non alcoholic fatty liver disease (NAFLD) has increased to 25% in the general population and could double by 2030. Liver fibrosis is the main indicator of morbidity and mortality and recent estimations suggest a substantial number of individuals with undiagnosed advanced liver disease. Strategies to monitor advanced fibrosis are essential for early detection, referral, diagnosis and treatment in primary care and endocrine units, where NAFLD and consequently liver fibrosis are more prevalent. Blood-based non-invasive methods could be used to stratify patients according to the risk of the progression of fibrosis and combined with imaging techniques to improve stratification. Powerful new diagnostic tools such as MRE and PDFF are emerging and might prevent the need for liver biopsy in the near future. The current therapeutic landscape of NAFLD is rapidly evolving with an increasing number of molecules that treat key factors involved in its progression, but that still have a limited or no ability to effectively reverse fibrosis. Management of this disease will probably require a combination of sequential and personalized treatments as a result of its complex and dynamic pathophysiology. Lifestyle interventions are still the most effective therapeutic option and should be better integrated into patient management together with specific programs of bariatric endoscopy/surgery for morbidly obese patients. ; This project has been partially funded by the "Spanish Ministry of Economy, Innovation and Competition, the Instituto de Salud Carlos III" (PI19/01404, PI16/01842, PI19/00589, PI17/00535 and GLD19/00100), and the Andalussian government (Proyectos Estratégicos-Fondos Feder PE-0451-2018).

BACKGROUND--The study comprised three interrelated aims: (1) to ascertain (a) patient compliance with physiotherapy, exercise, enzyme and vitamin regimens, (b) how compliance was perceived by patients, and (c) the reasons for poor compliance (2) to identify demographic and clinical variables associated with compliance; and (3) to determine how accurately patient compliance can be predicted by carers. METHODS--Demographic and medical history data were obtained from medical records and a patient questionnaire. The data obtained included age, sex, employment status, inpatient or outpatient status, frequency of contact with the clinic, age at diagnosis, and the number of years practising physiotherapy. Measures of clinical status, including FEV1 and FVC percentage predicted, Shwachman score, and 24 hour sputum weight were recorded before completion of the questionnaire. The questionnaire, administered by a psychologist, assessed the reported degree of patient compliance, their perception of compliance, and their reasons for poor compliance. RESULTS--Sixty patients participated in the study and 51/60 and 41/55 patients were considered compliant with enzyme and exercise therapies, respectively. Compliance was lower with physiotherapy (32/60) and vitamin treatment (21/45). Patients reporting immediate benefits following exercise and physiotherapy were more compliant than those reporting no improvement. The perception by patients that compliance was sufficient ("about right") was physiotherapy 67%, exercise 37%, enzymes 78%, and vitamins 9%. Compliance was not influenced by demographic details nor by severity of disease, although patients producing large amounts of sputum and receiving help with physiotherapy were more compliant with physiotherapy. The physiotherapist and physician judged correctly the degree of compliance with physiotherapy in 83% and 75% of cases, respectively, and with exercise in 68% and 67% of cases, respectively. CONCLUSIONS--The reported degree of compliance and reasons for poor compliance were ...

Until recently, idiopathic pulmonary fibrosis (IPF) has been a devastating and generally fatal disease with no effective therapeutic. New developments in understanding the biology of the disease include a growing consensus that the lesions are mainly composed of cells that originated from resident fibroblasts. New developments in therapeutics include recommendations against several treatment regimes that have been previously used. On a positive note, the orally available drug pirfenidone has been approved for use in IPF in China, Japan, India, and the European Union, but not yet in the United States. Other possibilities for managing IPF include managing gastrointestinal reflux, and limiting excessive salt intake. A variety of potential therapeutics for IPF are in clinical trials; for instance in a Phase 1b trial, intravenous injections of a recombinant version of the normal human serum protein Serum Amyloid P (SAP, also known as PTX2) improved lung function in IPF patients.

Idiopathic pulmonary fibrosis (IPF) is marked by a very disappointing survival rate and still represents a clinical dilemma. According to the current pathogenic hypothesis, chronic damage of the alveolar epithelium is followed by abnormal tissue repair and impairment of the alveolar structure. This process is driven by pathogenic events very similar to cancer, including epigenetic and genetic changes, altered response to regulatory signals, abnormal expression of microRNAs and activation of specific signalling pathways. IPF also resembles cancer with regard to its poor response to medical treatment and prognosis, which is very often worse than many cancers. We have hypothesised that IPF might be assimilated to a neoproliferative disorder of the lung. Viewing IPF as a cancer-like disease may satisfy the need for a better understanding of the pathogenesis of IPF by exploiting the large amount of knowledge that cancer biology evokes. The recognition of common pathogenic pathways between the two diseases may stimulate new clinical trials with cancer drugs, different drug combinations and different lines of drugs, as already experimented in oncology. Moreover, the concept of IPF as a cancer-like disorder may improve the attention given to this dreadful disease on a public, political and healthcare level.

Between 2001 and 2005, 6,166 females underwent cystic fibrosis (CF) carrier screening at our institution. Only 36% were Caucasian. We identified 143 carrier females and subsequently tested 85 of their partners. The observed carrier frequency was not significantly different than expected for any racial or ethnic group tested. We identified 6 positive couples (5 Caucasian, 1 Arab American) and 1 affected fetus. In just under 4 years, our institution spent approximately USD 334,000 on CF population screening. Comparing this to the lifetime medical cost for a CF patient, CF population-based carrier screening is cost effective at our institution, despite the high number of non-Caucasians being screened.

Glycerol has been recently used to induce muscle adiposity in mice. However, its effects on the rat muscles have not been investigated previously. Therefore, we investigated the regeneration outcomes of rat muscles following glycerol-induced injury at different time points. Glycerol injection induced myofiber degeneration with extensive inflammatory infiltration on day 4 followed by appearance of regenerating myotubes on day 7 after injury without adipocyte infiltration. Meanwhile, a significant collagen deposition at early stage of regeneration that increased together with persistent inflammatory infiltration up to day 14 after injury indicates impaired regeneration. In conclusion, glycerol injury in rats is more suitable as a fibrosis-inducing model than in mice due to earlier and higher accumulation of fibrous tissue with lacking adipogenesis. ; JSPS KAKENHI Grant Number 16H02585 and the Egyptian Government. ; https://www.jstage.jst.go.jp ; am2019 ; Anatomy and Physiology