Next generation sequencing technology and genomewide data analysis: Perspectives for retinal research.

Prog Retin Eye Res. 2016 Jun 10;

Authors: Chaitankar V, Karakülah G, Ratnapriya R, Giuste FO, Brooks MJ, Swaroop A

Abstract
The advent of high throughput next generation sequencing (NGS) has accelerated the pace of discovery of disease-associated genetic variants and genomewide profiling of expressed sequences and epigenetic marks, thereby permitting systems-based analyses of ocular development and disease. Rapid evolution of NGS and associated methodologies presents significant challenges in acquisition, management, and analysis of large data sets and for extracting biologically or clinically relevant information. Here we illustrate the basic design of commonly used NGS-based methods, specifically whole exome sequencing, transcriptome, and epigenome profiling, and provide recommendations for data analyses. We briefly discuss systems biology approaches for integrating multiple data sets to elucidate gene regulatory or disease networks. While we provide examples from the retina, the NGS guidelines reviewed here are applicable to other tissues/cell types as well.

PMID: 27297499 [PubMed - as supplied by publisher]

Differential integrative omic analysis for mechanism insights and biomarker discovery of abnormal Savda syndrome and its unique Munziq prescription.

Sci Rep. 2016;6:27831

Authors: Guo X, Bakri I, Abudula A, Arken K, Mijit M, Mamtimin B, Upur H

Abstract
Research has shown that many cancers have acommon pathophysiological origin and often present with similar symptoms. In terms of Traditional Uighur Medicine (TUM) Hilit (body fluid) theory, abnormal Savda syndrome (ASS) formed by abnormal Hilit is the common phenotype of complex diseases and in particular tumours. Abnormal Savda Munziq (ASMq), one representative of TUM, has been effective in the treatment of cancer since ancient times. Despite the physiopathology of ASS, the relationship between causative factors and the molecular mechanism of ASMq are not fully understood. The current study expanded upon earlier work by integrating traditional diagnostic approaches with others utilizing systems biology technology for the analysis of proteomic (iTRAQ) and metabolomic ((1)H-NMR) profiles of Uighur Medicine target organ lesion (liver) tumours. The candidate proteins were analyzed by enrichment analysis of the biological process and biomarker filters. Subsequently, 3Omics web-based tools were used to determine the relationships between proteins and appropriate metabolites. ELISA assay and IHC methods were used to verify the proteomic result; the protein von Willebrand factor (vWF) may be the "therapeutic window" of ASMq and biomarkers of ASS. This study is likely to be of great significance for the standardization and modernization of TUM.

PMID: 27296761 [PubMed - in process]

Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era.

Brief Bioinform. 2016 Jun 12;

Authors: Cheng F, Hong H, Yang S, Wei Y

Abstract
Advances in next-generation sequencing technologies have generated the data supporting a large volume of somatic alterations in several national and international cancer genome projects, such as The Cancer Genome Atlas and the International Cancer Genome Consortium. These cancer genomics data have facilitated the revolution of a novel oncology drug discovery paradigm from candidate target or gene studies toward targeting clinically relevant driver mutations or molecular features for precision cancer therapy. This focuses on identifying the most appropriately targeted therapy to an individual patient harboring a particularly genetic profile or molecular feature. However, traditional experimental approaches that are used to develop new chemical entities for targeting the clinically relevant driver mutations are costly and high-risk. Drug repositioning, also known as drug repurposing, re-tasking or re-profiling, has been demonstrated as a promising strategy for drug discovery and development. Recently, computational techniques and methods have been proposed for oncology drug repositioning and identifying pharmacogenomics biomarkers, but overall progress remains to be seen. In this review, we focus on introducing new developments and advances of the individualized network-based drug repositioning approaches by targeting the clinically relevant driver events or molecular features derived from cancer panomics data for the development of precision oncology drug therapies (e.g. one-person trials) to fully realize the promise of precision medicine. We discuss several potential challenges (e.g. tumor heterogeneity and cancer subclones) for precision oncology. Finally, we highlight several new directions for the precision oncology drug discovery via biotherapies (e.g. gene therapy and immunotherapy) that target the 'undruggable' cancer genome in the functional genomics era.

PMID: 27296652 [PubMed - as supplied by publisher]

A Systems Biology Approach to Reveal Putative Host-Derived Biomarkers of Periodontitis by Network Topology Characterization of MMP-REDOX/NO and Apoptosis Integrated Pathways.

Front Cell Infect Microbiol. 2015;5:102

Authors: Zeidán-Chuliá F, Gürsoy M, Neves de Oliveira BH, Özdemir V, Könönen E, Gürsoy UK

Abstract
Periodontitis, a formidable global health burden, is a common chronic disease that destroys tooth-supporting tissues. Biomarkers of the early phase of this progressive disease are of utmost importance for global health. In this context, saliva represents a non-invasive biosample. By using systems biology tools, we aimed to (1) identify an integrated interactome between matrix metalloproteinase (MMP)-REDOX/nitric oxide (NO) and apoptosis upstream pathways of periodontal inflammation, and (2) characterize the attendant topological network properties to uncover putative biomarkers to be tested in saliva from patients with periodontitis. Hence, we first generated a protein-protein network model of interactions ("BIOMARK" interactome) by using the STRING 10 database, a search tool for the retrieval of interacting genes/proteins, with "Experiments" and "Databases" as input options and a confidence score of 0.400. Second, we determined the centrality values (closeness, stress, degree or connectivity, and betweenness) for the "BIOMARK" members by using the Cytoscape software. We found Ubiquitin C (UBC), Jun proto-oncogene (JUN), and matrix metalloproteinase-14 (MMP14) as the most central hub- and non-hub-bottlenecks among the 211 genes/proteins of the whole interactome. We conclude that UBC, JUN, and MMP14 are likely an optimal candidate group of host-derived biomarkers, in combination with oral pathogenic bacteria-derived proteins, for detecting periodontitis at its early phase by using salivary samples from patients. These findings therefore have broader relevance for systems medicine in global health as well.

PMID: 26793622 [PubMed - indexed for MEDLINE]

Changes in lipid metabolism and β-adrenergic response of adipose tissues of periparturient dairy cows affected by an energy-dense diet and nicotinic acid supplementation.

J Anim Sci. 2015 Aug;93(8):4012-22

Authors: Kenéz Á, Tienken R, Locher L, Meyer U, Rizk A, Rehage J, Dänicke S, Huber K

Abstract
Dairy cattle will mobilize large amounts of body fat during early lactation as an effect of decreased lipogenesis and increased lipolysis. Regulation of lipid metabolism involves fatty acid synthesis from acetate and β-adrenergic-stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in adipocytes. Although basic mechanisms of mobilizing fat storage in transition cows are understood, we lack a sufficiently detailed understanding to declare the exact regulatory network of these in a broad range of dairy cattle. The objective of the present study was to quantify 1) protein abundance of fatty acid synthase (FAS), 2) extent of phosphorylation of HSL and perilipin in vivo, and 3) β-adrenergic stimulated lipolytic response of adipose tissues in vitro at different stages of the periparturient period. We fed 20 German Holstein cows an energy-dense or an energetically adequate diet prepartum and 0 or 24 g/d nicotinic acid (NA) supplementation. Biopsy samples of subcutaneous and retroperitoneal adipose tissue were obtained at d 42 prepartum (d -42) and at d 1, 21, and 100 postpartum (d +1, d +21, d +100, respectively). To assess β-adrenergic response, tissue samples were incubated with 1 μ isoproterenol for 90 min at 37°C. The NEFA and glycerol release, as well as HSL and perilipin phosphorylation, was measured as indicators of in vitro stimulated lipolysis. In addition, protein expression of FAS and extent of HSL and perilipin phosphorylation were measured in fresh, nonincubated samples. There was no effect of dietary energy density or NA on the observed variables. The extent of HSL and perilipin phosphorylation under isoproterenol stimulation was strongly correlated with the release of NEFA and glycerol, consistent with the functional link between β-adrenergic-stimulated protein phosphorylation and lipolysis. In the nonincubated samples, FAS protein expression was decreased at d +1 and d +21, whereas HSL and perilipin phosphorylation increased from d -42 to d +1 and remained at an increased level throughout the first 100 d of lactation. In vitro lipolytic response was significant in prepartum samples at times when in vivo lipolysis was only minimally activated by phosphorylation. These data extend our understanding of the complex nature of control of lipolysis and lipogenesis in dairy cows and could be useful to the ongoing development of systems biology models of metabolism to help improve our quantitative knowledge of the cow.

PMID: 26440181 [PubMed - indexed for MEDLINE]

Systematic Mapping of Kinase Addiction Combinations in Breast Cancer Cells by Integrating Drug Sensitivity and Selectivity Profiles.

Chem Biol. 2015 Aug 20;22(8):1144-55

Authors: Szwajda A, Gautam P, Karhinen L, Jha SK, Saarela J, Shakyawar S, Turunen L, Yadav B, Tang J, Wennerberg K, Aittokallio T

Abstract
Chemical perturbation screens offer the possibility to identify actionable sets of cancer-specific vulnerabilities. However, most inhibitors of kinases or other cancer targets result in polypharmacological effects, which complicate the identification of target dependencies directly from the drug-response phenotypes. In this study, we developed a chemical systems biology approach that integrates comprehensive drug sensitivity and selectivity profiling to provide functional insights into both single and multi-target oncogenic signal addictions. When applied to 21 breast cancer cell lines, perturbed with 40 kinase inhibitors, the subtype-specific addiction patterns clustered in agreement with patient-derived subtypes, while showing considerable variability between the heterogeneous breast cancers. Experimental validation of the top predictions revealed a number of co-dependencies between kinase targets that led to unexpected synergistic combinations between their inhibitors, such as dasatinib and axitinib in the triple-negative basal-like HCC1937 cell line.

PMID: 26211361 [PubMed - indexed for MEDLINE]

DermO; an ontology for the description of dermatologic disease.

J Biomed Semantics. 2016;7:38

Authors: Fisher HM, Hoehndorf R, Bazelato BS, Dadras SS, King LE, Gkoutos GV, Sundberg JP, Schofield PN

Abstract
BACKGROUND: There have been repeated initiatives to produce standard nosologies and terminologies for cutaneous disease, some dedicated to the domain and some part of bigger terminologies such as ICD-10. Recently, formally structured terminologies, ontologies, have been widely developed in many areas of biomedical research. Primarily, these address the aim of providing comprehensive working terminologies for domains of knowledge, but because of the knowledge contained in the relationships between terms they can also be used computationally for many purposes.
RESULTS: We have developed an ontology of cutaneous disease, constructed manually by domain experts. With more than 3000 terms, DermO represents the most comprehensive formal dermatological disease terminology available. The disease entities are categorized in 20 upper level terms, which use a variety of features such as anatomical location, heritability, affected cell or tissue type, or etiology, as the features for classification, in line with professional practice and nosology in dermatology. Available in OBO flatfile and OWL 2 formats, it is integrated semantically with other ontologies and terminologies describing diseases and phenotypes. We demonstrate the application of DermO to text mining the biomedical literature and in the creation of a network describing the phenotypic relationships between cutaneous diseases.
CONCLUSIONS: DermO is an ontology with broad coverage of the domain of dermatologic disease and we demonstrate here its utility for text mining and investigation of phenotypic relationships between dermatologic disorders. We envision that in the future it may be applied to the creation and mining of electronic health records, clinical training and basic research, as it supports automated inference and reasoning, and for the broader integration of skin disease information with that from other domains.

PMID: 27296450 [PubMed - in process]

A Relation Extraction Framework for Biomedical Text Using Hybrid Feature Set.

Comput Math Methods Med. 2015;2015:910423

Authors: Muzaffar AW, Azam F, Qamar U

Abstract
The information extraction from unstructured text segments is a complex task. Although manual information extraction often produces the best results, it is harder to manage biomedical data extraction manually because of the exponential increase in data size. Thus, there is a need for automatic tools and techniques for information extraction in biomedical text mining. Relation extraction is a significant area under biomedical information extraction that has gained much importance in the last two decades. A lot of work has been done on biomedical relation extraction focusing on rule-based and machine learning techniques. In the last decade, the focus has changed to hybrid approaches showing better results. This research presents a hybrid feature set for classification of relations between biomedical entities. The main contribution of this research is done in the semantic feature set where verb phrases are ranked using Unified Medical Language System (UMLS) and a ranking algorithm. Support Vector Machine and Naïve Bayes, the two effective machine learning techniques, are used to classify these relations. Our approach has been validated on the standard biomedical text corpus obtained from MEDLINE 2001. Conclusively, it can be articulated that our framework outperforms all state-of-the-art approaches used for relation extraction on the same corpus.

PMID: 26347797 [PubMed - indexed for MEDLINE]

Negative symptoms in schizophrenia: a study in a large clinical sample of patients using a novel automated method.

BMJ Open. 2015;5(9):e007619

Authors: Patel R, Jayatilleke N, Broadbent M, Chang CK, Foskett N, Gorrell G, Hayes RD, Jackson R, Johnston C, Shetty H, Roberts A, McGuire P, Stewart R

Abstract
OBJECTIVES: To identify negative symptoms in the clinical records of a large sample of patients with schizophrenia using natural language processing and assess their relationship with clinical outcomes.
DESIGN: Observational study using an anonymised electronic health record case register.
SETTING: South London and Maudsley NHS Trust (SLaM), a large provider of inpatient and community mental healthcare in the UK.
PARTICIPANTS: 7678 patients with schizophrenia receiving care during 2011.
MAIN OUTCOME MEASURES: Hospital admission, readmission and duration of admission.
RESULTS: 10 different negative symptoms were ascertained with precision statistics above 0.80. 41% of patients had 2 or more negative symptoms. Negative symptoms were associated with younger age, male gender and single marital status, and with increased likelihood of hospital admission (OR 1.24, 95% CI 1.10 to 1.39), longer duration of admission (β-coefficient 20.5 days, 7.6-33.5), and increased likelihood of readmission following discharge (OR 1.58, 1.28 to 1.95).
CONCLUSIONS: Negative symptoms were common and associated with adverse clinical outcomes, consistent with evidence that these symptoms account for much of the disability associated with schizophrenia. Natural language processing provides a means of conducting research in large representative samples of patients, using data recorded during routine clinical practice.

PMID: 26346872 [PubMed - indexed for MEDLINE]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/15

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back.

Trends Pharmacol Sci. 2016 Jun 10;

Authors: Yadav AK, Srikrishna S, Gupta SC

Abstract
The fruit fly Drosophila melanogaster has been used for modeling cancer and as an in vivo tool for the validation and/or development of cancer therapeutics. The impetus for the use of Drosophila in cancer research stems from the high conservation of its signaling pathways, lower genetic redundancy, short life cycle, genetic amenability, and ease of maintenance. Several cell signaling pathways in Drosophila have been used for cancer drug development. The efficacy of combination therapy and uptake/bioavailability of drugs have also been studied. Drosophila has been validated using several FDA-approved drugs, suggesting a potential application of this model in drug repurposing. The model is emerging as a powerful tool for high-throughput screening and should significantly reduce the cost and time associated with drug development. In this review we discuss the applications of Drosophila in cancer drug development. The advantages and limitations of the model are discussed.

PMID: 27298020 [PubMed - as supplied by publisher]

Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era.

Brief Bioinform. 2016 Jun 12;

Authors: Cheng F, Hong H, Yang S, Wei Y

Abstract
Advances in next-generation sequencing technologies have generated the data supporting a large volume of somatic alterations in several national and international cancer genome projects, such as The Cancer Genome Atlas and the International Cancer Genome Consortium. These cancer genomics data have facilitated the revolution of a novel oncology drug discovery paradigm from candidate target or gene studies toward targeting clinically relevant driver mutations or molecular features for precision cancer therapy. This focuses on identifying the most appropriately targeted therapy to an individual patient harboring a particularly genetic profile or molecular feature. However, traditional experimental approaches that are used to develop new chemical entities for targeting the clinically relevant driver mutations are costly and high-risk. Drug repositioning, also known as drug repurposing, re-tasking or re-profiling, has been demonstrated as a promising strategy for drug discovery and development. Recently, computational techniques and methods have been proposed for oncology drug repositioning and identifying pharmacogenomics biomarkers, but overall progress remains to be seen. In this review, we focus on introducing new developments and advances of the individualized network-based drug repositioning approaches by targeting the clinically relevant driver events or molecular features derived from cancer panomics data for the development of precision oncology drug therapies (e.g. one-person trials) to fully realize the promise of precision medicine. We discuss several potential challenges (e.g. tumor heterogeneity and cancer subclones) for precision oncology. Finally, we highlight several new directions for the precision oncology drug discovery via biotherapies (e.g. gene therapy and immunotherapy) that target the 'undruggable' cancer genome in the functional genomics era.

PMID: 27296652 [PubMed - as supplied by publisher]

14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/06/14

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Glipizide suppresses prostate cancer progression in the TRAMP model by inhibiting angiogenesis.

Sci Rep. 2016;6:27819

Authors: Qi C, Bin Li, Yang Y, Yang Y, Li J, Zhou Q, Wen Y, Zeng C, Zheng L, Zhang Q, Li J, He X, Zhou J, Shao C, Wang L

Abstract
Drug repurposing of non-cancer drugs represents an attractive approach to develop new cancer therapy. Using the TRAMP transgenic mouse model, glipizide, a widely used drug for type 2 diabetes mellitus, has been identified to suppress prostate cancer (PC) growth and metastasis. Angiogenesis is intimately associated with various human cancer developments. Intriguingly, glipizide significantly reduces microvessel density in PC tumor tissues, while not inhibiting prostate cancer cell proliferation from the MTT assay and flow cytometry investigation. Moreover, glipizide inhibits the tubular structure formation of human umbilical vein endothelial cells by regulating the HMGIY/Angiopoietin-1 signaling pathway. Taken together, these results demonstrate that glipizide has the potential to be repurposed as an effective therapeutic for the treatment of PC by targeting tumor-induced angiogenesis.

PMID: 27292155 [PubMed - in process]

Progresses in treating agitation: a major clinical challenge in Alzheimer's disease.

Expert Opin Pharmacother. 2015;16(17):2581-8

Authors: Panza F, Solfrizzi V, Seripa D, Imbimbo BP, Santamato A, Lozupone M, Prete C, Greco A, Pilotto A, Logroscino G

Abstract
INTRODUCTION: Treatment of neuropsychiatric symptoms (NPS) represents a major clinical challenge in Alzheimer's disease (AD). Agitation and aggression are frequently seen during institutionalization and increase patient morbidity and mortality and caregiver burden. Off-label use of atypical antipsychotics for treating agitation in AD showed only modest clinical benefits, with high side-effect burden and risk of mortality. Non-pharmacological treatment approaches have become the preferred first-line option. When such treatment fails, pharmacological options are often used. Therefore, there is an urgent need to identify effective and safe pharmacological treatments for efficiently treating agitation and aggression in AD and dementia.
AREAS COVERED: Emerging evidence on the neurobiological substrates of agitation in AD has led to several recent clinical trials of repositioned and novel therapeutics for these NPS in dementia as an alternative to antipsychotics. We operated a comprehensive literature search for published articles evaluating pharmacological interventions for agitation in AD, with a review of recent clinical trials on mibampator, dextromethorphan/quinidine, cannabinoids, and citalopram.
EXPERT OPINION: Notwithstanding the renewed interest for the pharmacological treatment of agitation in AD, progresses have been limited. A small number and, sometimes methodologically questionable, randomized controlled trials (RCTs) have produced disappointing results. However, recently completed RCTs on novel or repositioned drugs (mibampator, dextromethorphan/quinidine, cannabinoids, and citalopram) showed some promise in treating agitation in AD, but still with safety concerns. Further evidence will come from ongoing Phase II and III trials on promising novel drugs for treating these distressing symptoms in patients with AD and dementia.

PMID: 26389682 [PubMed - indexed for MEDLINE]

Pharmacogenetic considerations in the treatment of Alzheimer's disease.

Pharmacogenomics. 2016 Jun 13;

Authors: Cacabelos R, Torrellas C, Teijido O, Carril JC

Abstract
The practical pharmacogenetics of Alzheimer's disease (AD) is circumscribed to acetylcholinesterase inhibitors (AChEIs) and memantine. However, pharmacogenetic procedures should be applied to novel strategies in AD therapeutics including: novel AChEIs and neurotransmitter regulators, anti-Aβ treatments, anti-tau treatments, pleiotropic products, epigenetic drugs and combination therapies. Genes involved in the pharmacogenetic network are under the influence of the epigenetic machinery which regulates gene expression transcriptionally and post-transcriptionally, configuring the fundamentals of pharmacoepigenomics. Over 60% of AD patients present concomitant pathologies demanding additional treatments which increase the likelihood of drug-drug interactions. Lipid metabolism dysfunction is a pathogenic mechanism inherent to AD neurodegeneration. The therapeutic response to hypolipidemic compounds is influenced by the APOE and CYP genotypes. The development of novel compounds and the use of combination/multifactorial treatments require the implantation of pharmacogenomic procedures for the avoidance of ADRs and the optimization of therapeutics.

PMID: 27291247 [PubMed - as supplied by publisher]

Will personalized drugs for cardiovascular disease become an option? - Defining 'Evidence-based personalized medicine' for its implementation and future use.

Expert Opin Pharmacother. 2015;16(17):2549-52

Authors: de Denus S, Dubé MP, Tardif JC

Abstract
It is generally accepted that the implementation of pharmacogenomics and, more broadly, personalized medicine will have to be 'evidence-based'. However, there is a lack of consensus on the level of evidence required to justify the use of pharmacogenomic testing in clinical practice. In the cardiovascular field, this lack of agreement has led to somewhat contradicting recommendations by different organizations regarding the clinical utility and use of pharmacogenomic tests or information. Here, we argue that randomized, controlled trials are paramount in order to enable and accelerate the widespread implementation of pharmacogenomics, not only to demonstrate the clinical efficacy and cost-effectiveness of such tests, but because such level of evidence is required to support the considerable changes associated with the implantation of pharmacogenomics in clinical practice.

PMID: 26371722 [PubMed - indexed for MEDLINE]

Expiratory Flow Limitation for Monitoring Cystic Fibrosis. Ready for the Starting Gun?

Ann Am Thorac Soc. 2016 Jun;13(6):770-771

Authors: Bush A

PMID: 27295150 [PubMed - as supplied by publisher]

Cystic Fibrosis Revisited - a Review Study.

Med Chem. 2016 Jun 8;

Authors: Kuca K, Klimova B, Novotny M, Maresova P

Abstract
BACKGROUND: Cystic fibrosis (CF) is an incurable, chronic disease, which causes severe damages to respiratory and digestive tracts. It is the most common genetically inherited disease among caucasians. This disease is caused by defects in CF genes, the so-called mutations in cystic fibrosis transmembrane conductance regulator (CFTR) gene population. At present over 100,000 people suffer from this disease worldwide.
OBJECTIVE: The purpose of this review study is to describe the pathophysiology of CF and provide the latest information on its diagnosis and treatment therapies with respect to the improvement of patient's quality of life and emphasis on targeted specialized care.
METHOD: The methodological approaches include a method of literature review of available sources exploring the issue of cystic fibrosis both from a global and specific perspective point of view. A search was performed in the databases PubMed, MEDLINE, Web of Science, Scopus, Springer and ScienceDirect. Furthermore, other sources cited in the analyzed studies were also examined. On the basis of evaluation of these literature sources, the research issue was explored.
RESULTS: The main benefits (e.g., specialized centres for the treatment of CF exist or a new breakthrough in the gene therapy of CF has been made) and limitations (e.g., comorbidity of CF, lifelong and costly treatment, or adverse impact on patient's and caregiver's quality of life) in the treatment of narcolepsy are highlighted.
CONCLUSION: CF requires an integrated treatment approach in specialized CF centers, involving various factors contributing to a better patient's state of health in the form of relevant and well-balanced non-pharmacological and pharmacological therapies. In addition, further large scale clinical trials are needed in order to develop compounds that are aimed at the most common classes of CFTR.

PMID: 27292156 [PubMed - as supplied by publisher]

[Italian Cystic Fibrosis Register - Report 2010].

Epidemiol Prev. 2016 Mar-Apr;40(2 Suppl 2):1-47

Authors: Amato A, Ferrigno L, Salvatore M, Toccaceli V, Gruppo di lavoro RIFC/ICFR Working Group

Abstract
UNLABELLED: The Italian National CF Registry (INCFR) is based on the official agreement between the clinicians of the Italian National Referral Centers for Cystic Fibrosis and the researchers of the Istituto Superiore di Sanità (National Center for Rare Diseases; National Center for Epidemiology, Surveillance and Health Care Promotion). OBJECTIVES The main aim of INCFR is to contribute to the improvement in CF patients health care and clinical management through: i. the estimates of CF prevalence and incidence in Italy; ii. the analyses of medium and long term clinical and epidemiological trends of the disesase; iii. the identification of the main health care needs at regional and national level to contribute to the Health Care programmes and to the distribution of resources. MATERIALS AND METHODS Analyses and results described in the present Report are referred to patients in charge to the Italian National Referral Centers for Cystic Fibrosis in 2010. Data were sent by Centers by means of a specific software (Camilla, Ibis Informatica). The Italian National Referral Centers for Cystic Fibrosis sent a total of 5,271 individual records; 1,112 records were excluded from the analyses due to restricted inclusion criteria. The total number of patients included in INCFR for analyses is 4,159. RESULTS INCFR database includes all prevalent cases at 1th January 2010 as well as all new diagnoses done in 2010. The present Report has been organized into 9 sections. 1. Demography: estimated 2010 CF prevalence was 7/100,000 residents in Italy; 52% of the patients were male, CF distribution showed higher frequency in patients aged 7 to 35 years. In 2010, 48.9% of the patients were more than 18 years old. 2. Diagnoses: most of the CF patients were diagnosed before two years of age (66.7%); a significant percentage of patients (11.4%) was diagnosed in adult-age. 3. New diagnoses (2010): new diagnoses were 168. Sixty-five percent of them was diagnosed before the second year of age and 17%in adulthood. No differences were observed between male and female. Incidence at birth was estimated 1/4,854 living births. 4.
GENETICS: in 95.9% of patients, 2 (or more) CFTR mutations were identified. [delta]508F mutation was the most frequent (45.1%). 5. Respiratory function: analyses were performed on 2,966 out of 3,341 patients aged 7 years or older. FEV1 (Forced Expiratory Volume in the first second) scores progressively decreased before adult age, in accordance with the natural history of the disease. 6. Nutrition: most critical periods are during the first 6 months of life and during adolescence. Fourteen per cent of the patients within 2-18 years resulted malnourished. From 18 years onwards, optimal BodyMass Index (BMI) values were detected in 36.5%of males and in 28%of females. BMI also improved during age. 7. Transplantation: in 2010, 20 patients (10 males and 10 females) were bi-pulmunary transplanted; age was comprised between 11 and 46 years, median age at transplantation was 27.5 years. Eleven out of the 20 patients resulted still alive on the 31th December 2010. 8. Microbiology: analyses were performed on 3.272 patients (887 did not report these data) and were exclusively referred to tests performed in 2010. A percentage of 34 patients, younger than 18 years of age, was characterized by the presence of Pseudomonas aeruginosa compared to 61.8% of the older patients. Prevalence of Burkholderia Cepacia was 0.8% in patients aged up to 17 years; in patients aged more than 17 years, prevalence was 6.8%. Staphylococcus aureus meticillino sensitive prevalence was not correlated with patients' age. 9.
MORTALITY: 34 patients aged from 0 to 45 years died in 2010 (16 males and 18 females). Respiratory insufficiency was the main cause of death (73.5%). CONCLUSIONS The report aims at being an instrument for CF community, with particular attention to the needs of patients and their families. Information collected within INCFR are an important starting point for further studies from health care perspectives. Finally, INCFR represents an important tool to foster research and innovative treatment for CF, as the rareness of the disease is a constraint to clinical trials and other studies set-up. A significant subset of data are regularly sent to the European Registry of Cystic Fibrosis.

PMID: 27291389 [PubMed - in process]