Features of Severe Liver Disease With Portal Hypertension in Patients With Cystic Fibrosis

Liver disease is the third leading cause of death in patients with cystic fibrosis (CF), but features of patients with CF, severe liver disease, and portal hypertension have not been fully characterized

Immunoreactive trypsinogen levels in newborn screened infants with an inconclusive diagnosis of cystic fibrosis.

BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction in each individual and therefore would help to identify those with CRMS/CSPID who are later at risk for meeting the criteria of CF. METHODS: In this longitudinal, prospective study, infants with CRMS/CFSPID and CF were recruited and followed in 9 CF clinics (Canada and Italy). We compared NBS IRT levels between CF and CRMS/CFSPID, and between children with CRMS/CFSPID→CF and CRMS/CFSPID→CRMS/CFSPID during the period of June 2007 to April 2016. RESULTS: Ninety eight CRMS/CFSPID and 120 CF subjects were enrolled. During the study period, 14 (14.3%) CRMS/CFSPID subjects fulfilled the diagnostic criteria for CF (CRMS/CFSPID→CF), while the diagnosis remained uncertain (CRMS/CFSPID→ CRMS/CFSPID) in 84 (85.7%) subjects. Significantly higher NBS IRT concentrations (ng/ml) were present in CF than CRMS/CFPSID (median (interquartile range): 143.8 (99.8-206.2) vs. 75.0 (61.0-105.9); P \u3c 0.0001). Infants with CRMS/CFSPID→CF (n = 14) had significantly higher NBS IRT concentrations (ng/ml) than CRMS/CFSPID→ CRMS/CFSPID (n = 83) (median (interquartile range): 108.9 (72.3-126.8) vs. 73.7(60.0-96.0); P = 0.02). CONCLUSIONS: Amongst infants who tested positive on NBS for CF, there is a gradation of elevated NBS IRT concentrations. Infants with CF have higher NBS IRT levels than CRMS/CFPSID, and higher NBS IRT concentrations were present in infants with CRMS/CFSPID→CF than CRMS/CFSPID→ CRMS/CFSPID. NBS IRT concentrations, in concert with other factors, may have the potential to predict the likelihood of CF amongst infants with CRMS/CFSPID

Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine involvement in patients with multiple myeloma

BACKGROUND: Recently, radiopharmaceutical scanning with Tc-99m-MIBI was reported to depict areas with active bone disease in multiple myeloma (MM) with both high sensitivity and specificity. This observation was explained by the uptake of Tc-99m-MIBI by neoplastic cells. The present investigation evaluates whether Tc-99m-MIBI imaging and magnetic resonance imaging (MRI) perform equally well in detecting myelomatous bone marrow lesions. METHODS: In 21 patients with MM, MRIs of the vertebral region TH12 to S1 and whole body scans with Tc-99m-MIBI were done. RESULTS: Tc-99m-MIBI scanning missed bone marrow infiltration in 43 of 87 vertebrae (50.5%) in which MRI showed neoplastic bone marrow involvement. In patients with disease stage I+II, Tc-99m-MIBI scanning was negative in all of 24 vertebrae infiltrated according to MRI. In patients with disease stage III, Tc-99m-MIBI scanning detected 44 of 63 (70%) vertebrae involved by neoplastic disease. CONCLUSION: Tc-99m-MIBI scanning underestimated the extent of myelomatous bone marrow infiltration in the spine, especially in patients with low disease stage

The Ongoing Confusion Over Ongoing Royalties 1

In eBay Inc. v. MercExchange LLC, the Supreme Court correctly concluded that courts had both the power and the responsibility to decide whether a successful patent owner needed injunctive relief, and whether the imposition of that relief would unduly harm either the defendant or the public. 3 The application of the traditional four-factor equity test has led, for the first time, to a significant number of cases in which courts find patent infringement but refuse to enjoin continued infringement. That in turn has raised the question "what happens then?" The basic answer seems clear as a matter of policy: while the patentee can't enjoin infringement, the infringer should have to pay for the right to continue infringing. But that basic answer conceals three subsidiary issues: do courts have the authority to award an ongoing royalty, who decides what that royalty should be, and how should that royalty be calculated. To date, courts have largely ignored the first and second questions. While they have addressed the third, they haven't done so in a particularly satisfactory manner. In this article I endeavor to answer these questions

A Fully Integrated Real-Time Detection, Diagnosis, and Control of Community Diarrheal Disease Clusters and Outbreaks (the INTEGRATE Project):Protocol for an Enhanced Surveillance System

BACKGROUND:Diarrheal disease, which affects 1 in 4 people in the United Kingdom annually, is the most common cause of outbreaks in community and health care settings. Traditional surveillance methods tend to detect point-source outbreaks of diarrhea and vomiting; they are less effective at identifying low-level and intermittent food supply contamination. Furthermore, it can take up to 9 weeks for infections to be confirmed, reducing slow-burn outbreak recognition, potentially impacting hundreds or thousands of people over wide geographical areas. There is a need to address fundamental problems in traditional diarrheal disease surveillance because of underreporting and subsequent unconfirmed infection by patients and general practitioners (GPs); varying submission practices and selective testing of samples in laboratories; limitations in traditional microbiological diagnostics, meaning that the timeliness of sample testing and etiology of most cases remains unknown; and poorly integrated human and animal surveillance systems, meaning that identification of zoonoses is delayed or missed. OBJECTIVE:This study aims to detect anomalous patterns in the incidence of gastrointestinal disease in the (human) community; to target sampling; to test traditional diagnostic methods against rapid, modern, and sensitive molecular and genomic microbiology methods that identify and characterize responsible pathogens rapidly and more completely; and to determine the cost-effectiveness of rapid, modern, sensitive molecular and genomic microbiology methods. METHODS:Syndromic surveillance will be used to aid identification of anomalous patterns in microbiological events based on temporal associations, demographic similarities among patients and animals, and changes in trends in acute gastroenteritis cases using a point process statistical model. Stool samples will be obtained from patients' consulting GPs, to improve the timeliness of cluster detection and characterize the pathogens responsible, allowing health protection professionals to investigate and control outbreaks quickly, limiting their size and impact. The cost-effectiveness of the proposed system will be examined using formal cost-utility analysis to inform decisions on national implementation. RESULTS:The project commenced on April 1, 2013. Favorable approval was obtained from the Research Ethics Committee on June 15, 2015, and the first patient was recruited on October 13, 2015, with 1407 patients recruited and samples processed using traditional laboratory techniques as of March 2017. CONCLUSIONS:The overall aim of this study is to create a new One Health paradigm for detecting and investigating diarrhea and vomiting in the community in near-real time, shifting from passive human surveillance and management of laboratory-confirmed infection toward an integrated, interdisciplinary enhanced surveillance system including management of people with symptoms. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/13941

Alinhamento interpessoal, representacional e morfossintático na Gramática Discursivo-Funcional

Este artigo se debruça sobre o mapeamento entre os Níveis Interpessoal, Representacional e Morfossintático da gramática, o chamado alinhamento, segundo o arcabouço da Gramática Discursivo-Funcional (GDF). Propõe uma tipologia das línguas baseada no que a sua organização morfossintática codifica: distinções pragmáticas (p.ex. em Tagalo), distinções semânticas (p.ex. em Achém), ou distinções inerentes à morfossintaxe (p.ex. em Inglês, Basco ou a língua Kham). A inclusão tanto do Sujeito como do Objeto e de línguas tanto acusativas como ergativas no tratamento do alinhamento morfossintático permitiu-nos abranger tipos tipologicamente mais variáveis e demonstrar o potencial da GDF para a análise contrastiva das línguas.<br>Within the framework of Functional Discourse Grammar (FDG), alignment concerns the relations between the Interpersonal, Representational and Morphosyntactic Levels of grammar. This article proposes a typology of languages based upon what we find to be encoded in their morphosyntactic organization: pragmatic distinctions (as in Tagalog), semantic distinctions (as in Acheh), or distinctions inherent to the morphosyntax (as in English, Basque and Kham). By including both subject and object, and both accusative and ergative languages in our treatment of morphosyntactic alignment, we provide a better coverage of typological variation and show the potential of FDG for cross-linguistic analysis

Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report

Newborn screening (NBS) for cystic fibrosis (CF) is increasingly being implemented and is soon likely to be in use throughout the United States, because early detection permits access to specialized medical care and improves outcomes. The diagnosis of CF is not always straightforward, however. The sweat chloride test remains the gold standard for CF diagnosis but does not always give a clear answer. Genotype analysis also does not always provide clarity; more than 1500 mutations have been identified in the CF transmembrane conductance regulator (CFTR) gene, not all of which result in CF. Harmful mutations in the gene can present as a spectrum of pathology ranging from sinusitis in adulthood to severe lung, pancreatic, or liver disease in infancy. Thus, CF identified postnatally must remain a clinical diagnosis. To provide guidance for the diagnosis of both infants with positive NBS results and older patients presenting with an indistinct clinical picture, the Cystic Fibrosis Foundation convened a meeting of experts in the field of CF diagnosis. Their recommendations, presented herein, involve a combination of clinical presentation, laboratory testing, and genetics to confirm a diagnosis of CF

A novel lung disease phenotype adjusted for mortality attrition for cystic fibrosis Genetic modifier studies

Genetic studies of lung disease in Cystic Fibrosis are hampered by the lack of a severity measure that accounts for chronic disease progression and mortality attrition. Further, combining analyses across studies requires common phenotypes that are robust to study design and patient ascertainment