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BACKGROUND: People with coeliac disease (CD) are at increased risk of osteoporosis and fractures. Currently, baseline dual-energy X-ray absorptiometry (DXA) is recommended for all patients with newly diagnosed CD. We aimed to determine the prevalence of osteoporosis and the clinical utility of the Fracture Risk Assessment Tool (FRAX) in predicting major osteoporotic fractures (MOF) in patients with biopsy-proven CD. METHODS: We retrospectively collected data for consecutive adult patients with biopsy-proven CD between 2001 and 2015 who underwent DXA scanning within 1 year of diagnosis and were followed up for a minimum of 7 years. Fracture risk was assessed using FRAX scores, and the incidence of major osteoporotic fractures during the follow-up period was analysed. RESULTS: A total of 593 patients (median age 45.0 years, 68.5% female) were included. The prevalence of osteopenia and osteoporosis were 32.3% and 14.5%, respectively. Increasing age (OR 1.06, p < .0001), decreasing BMI (OR 0.90, p = .003), and higher baseline immunoglobulin A-tissue tissue transglutaminase titre (OR 1.04, p = .03) were significantly associated with increased risk of osteoporosis. The sensitivity, specificity, positive and negative predictive values of the FRAX tool to predict MOF were 21.2%, 91.3%, 16.3%, 93.5%, respectively. A higher risk of fractures was associated with ongoing gluten exposure (OR 1.86, p = .02), previous fractures (OR 2.69, p = .005), and older age (OR 1.03, p < .0001). CONCLUSION: Osteoporosis is a common finding in patients with CD. The FRAX tool showed high specificity in predicting osteoporotic fractures and could be used to aid with patient selection for DXA scanning in some cases.
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BACKGROUND: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. METHODS: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. FINDINGS: Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. INTERPRETATION: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.
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Doença Celíaca , Duodeno , Transglutaminases , Humanos , Doença Celíaca/patologia , Doença Celíaca/diagnóstico , Doença Celíaca/dietoterapia , Feminino , Masculino , Adulto , Estudos de Casos e Controles , Duodeno/patologia , Adulto Jovem , Transglutaminases/imunologia , Imunoglobulina A/sangue , Proteínas de Ligação ao GTP/imunologia , Atrofia , Dieta Livre de Glúten , Mucosa Intestinal/patologia , Proteína 2 Glutamina gama-Glutamiltransferase , Gastroscopia , Pessoa de Meia-IdadeRESUMO
Hematospermia is a common, but anxiety-provoking genitourinary condition. In instances without spontaneous resolution, pharmacologic intervention with a 5-alpha reductase inhibitor has been shown to be successful. In cases of refractory hematospermia, robotic-assisted laparoscopic seminal vesiculectomy may provide a definitive treatment option. A robotic-assisted bilateral seminal vesiculectomy was performed on a 42-year-old male with refractory painless hematospermia after failing conservative management. Three months post-operatively, the patient reported resolution of hematospermia after six ejaculations with no impact on erectile function. The robotic-assisted approach is safe and feasible with good functional outcomes and reduced morbidity.
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OBJECTIVE: Persistent villous atrophy (pVA) in coeliac disease (CD) despite a gluten-free diet (GFD) has unclear meaning. We aimed to (i) study the relationship between pVA and long-term outcomes and (ii) develop a score to identify patients at risk of pVA. DESIGN: This is a multicentre retrospective-prospective study consisting of a study cohort (cohort 1) and an external validation cohort (cohort 2) of patients with biopsy-proven CD diagnosed between 2000 and 2021. Cohort 1 was used to (i) compare long-term outcomes between patients with and without pVA (Marsh ≥3a) at follow-up biopsy and (ii) to develop a score to evaluate the risk of pVA, which was validated in cohort 2. RESULTS: Of 2211 patients, 694 (31%) underwent follow-up duodenal biopsy and were included in the study cohort (491F, 44±16 years). 157/694 (23%) had pVA. Risk of complications (HR 9.53, 95% CI 4.77 to 19.04, p<0.001) and mortality (HR 2.93, 95% CI 1.43 to 6.02, p<0.01) were increased in patients with pVA. A 5-point score was developed and externally validated (receiver operating characteristic area under the curve 0.78, 95% CI 0.68 to 0.89) to stratify patients by risk of pVA: low (0-1 points, 5% pVA), intermediate (2 points, 16% pVA) and high (3-5 points, 73% pVA). Predictors for pVA used in the score were age at diagnosis ≥45 years (OR 2.01, 95% CI 1.21 to 3.34, p<0.01), classical pattern of CD (OR 2.14, 95% CI 1.28 to 3.58, p<0.01), lack of clinical response to GFD (OR 2.40, 95% CI 1.43 to 4.01, p<0.001) and poor GFD adherence (OR 48.9, 95% CI 26.1 to 91.8, p<0.001). CONCLUSIONS: Risk of complications and mortality were increased in patients with pVA. We developed a score to identify patients at risk of pVA and in need of histological reassessment and closer follow-up.
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Doença Celíaca , Humanos , Adulto , Pessoa de Meia-Idade , Doença Celíaca/complicações , Doença Celíaca/diagnóstico , Estudos Retrospectivos , Estudos Prospectivos , Estudos Longitudinais , Mucosa Intestinal/patologia , Atrofia/patologia , Dieta Livre de Glúten , BiópsiaRESUMO
BACKGROUND: Poor diet, alcohol use, and tobacco smoking have been identified as strong determinants of chronic diseases, such as cardiovascular disease, diabetes, and cancer. Smartphones have the potential to provide a real-time, pervasive, unobtrusive, and cost-effective way to measure these health behaviors and deliver instant feedback to users. Despite this, the validity of using smartphones to measure these behaviors is largely unknown. OBJECTIVE: The aim of our review is to identify existing smartphone-based approaches to measure these health behaviors and critically appraise the quality of their measurement properties. METHODS: We conducted a systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsycINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library databases in March 2020. Articles that were written in English; reported measuring diet, alcohol use, or tobacco use via a smartphone; and reported on at least one measurement property (eg, validity, reliability, and responsiveness) were eligible. The methodological quality of the included studies was assessed using the Consensus-Based Standards for the Selection of Health Measurement Instruments Risk of Bias checklist. Outcomes were summarized in a narrative synthesis. This systematic review was registered with PROSPERO, identifier CRD42019122242. RESULTS: Of 12,261 records, 72 studies describing the measurement properties of smartphone-based approaches to measure diet (48/72, 67%), alcohol use (16/72, 22%), and tobacco use (8/72, 11%) were identified and included in this review. Across the health behaviors, 18 different measurement techniques were used in smartphones. The measurement properties most commonly examined were construct validity, measurement error, and criterion validity. The results varied by behavior and measurement approach, and the methodological quality of the studies varied widely. Most studies investigating the measurement of diet and alcohol received very good or adequate methodological quality ratings, that is, 73% (35/48) and 69% (11/16), respectively, whereas only 13% (1/8) investigating the measurement of tobacco use received a very good or adequate rating. CONCLUSIONS: This review is the first to provide evidence regarding the different types of smartphone-based approaches currently used to measure key behavioral risk factors for chronic diseases (diet, alcohol use, and tobacco use) and the quality of their measurement properties. A total of 19 measurement techniques were identified, most of which assessed dietary behaviors (48/72, 67%). Some evidence exists to support the reliability and validity of using smartphones to assess these behaviors; however, the results varied by behavior and measurement approach. The methodological quality of the included studies also varied. Overall, more high-quality studies validating smartphone-based approaches against criterion measures are needed. Further research investigating the use of smartphones to assess alcohol and tobacco use and objective measurement approaches is also needed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-https://doi.org/10.1186/s13643-020-01375-w.
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Dieta , Smartphone , Comportamentos Relacionados com a Saúde , Humanos , Reprodutibilidade dos Testes , Uso de TabacoRESUMO
Hurthle cell tumors are rare follicular-derived thyroid neoplasms. Hurthle cell tumors may be benign or malignant. Workup includes imaging, fine needle aspiration, and treatment usually consists of observation versus thyroidectomy. We describe a case of Hurthle cell adenoma in an adolescent; to the best of our knowledge, this represents only the third case described in the English literature of adolescent Hurthle cell adenoma.
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Adenoma Oxífilo , Neoplasias da Glândula Tireoide , Adolescente , Humanos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Biópsia por Agulha Fina/métodos , Adenoma Oxífilo/patologiaRESUMO
BACKGROUND: The link between chronic diseases and the Big 6 lifestyle risk behaviors (ie, poor diet, physical inactivity, smoking, alcohol use, sedentary recreational screen time, and poor sleep) is well established. It is critical to target these lifestyle risk behaviors, as they often co-occur and emerge in adolescence. Smartphones have become an integral part of everyday life, and many adolescents already use mobile apps to monitor their lifestyle behaviors and improve their health. Smartphones may be a valuable platform for engaging adolescents with interventions to prevent key chronic disease risk behaviors. OBJECTIVE: The aim of this paper is to describe the development, usability, and acceptability of the Health4Life app, a self-monitoring smartphone app for adolescents that concurrently targets the Big 6 lifestyle behaviors. METHODS: The development of the Health4Life app was an iterative process conducted in collaboration with adolescents and experts. The development process consisted of three stages: scoping the literature; end user consultations, which included a web-based survey (N=815; mean age 13.89, SD 0.89 years) and a focus group (N=12) among adolescents; and app development and beta testing. Following this development work, 232 adolescents were asked to rate the usability and acceptability of the app. RESULTS: The process resulted in a self-monitoring smartphone app that allows adolescent users to track and set goals for the Big 6 health behaviors, using in-app rewards and notifications to enhance engagement. The overall adolescent feedback was positive in terms of user-friendly design, content, relevance, and helpfulness. Commonly identified areas for improvement were to increase interactive features and display recorded health behaviors differently to improve interpretability. CONCLUSIONS: The Health4Life app is a co-designed, self-monitoring smartphone app for adolescents that concurrently targets the Big 6 lifestyle behaviors. Adolescents rated the app as highly acceptable and usable. The app has the potential to efficiently and effectively modify important risk factors for chronic disease among young people and is currently being evaluated in a world-first trial of 6640 secondary school students in 71 schools across Australia.
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BACKGROUND: Six core behavioural risk factors (poor diet, physical activity, sedentary behaviour, alcohol misuse, smoking and unhealthy sleep patterns) have been identified as strong determinants of chronic disease, such as cardiovascular disease, diabetes and cancers. Smartphones have the potential to provide a real-time, pervasive, unobtrusive and cost-effective way to measure health behaviours and deliver instant feedback to users. Despite this, validity of using smartphones to measure these six key behaviours is largely unknown. The proposed systematic review aims to address this gap by identifying existing smartphone-based approaches to measure these health behaviours and critically appraising, comparing and summarizing the quality of their measurement properties. METHODS: A systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsychINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost) and IEEE Xplore Digital Library databases will be conducted from January 2007 to March 2020. Eligible studies will be those written in English that measure at least one of the six health behaviours of interest via a smartphone and report on at least one measurement property. The primary outcomes will be validity, reliability and/or responsiveness of these measurement approaches. A secondary outcome will be the feasibility (e.g. user burden, usability and cost) of identified approaches. No restrictions will be placed on the participant population or study design. Two reviewers will independently screen studies for eligibility, extract data and assess the risk of bias. The study methodological quality (or bias) will be appraised using an appropriate tool. Our results will be described in a narrative synthesis. If feasible, random effects meta-analysis will be conducted where appropriate. DISCUSSION: The results from this review will provide important information about the types of smartphone-based approaches currently available to measure the core behavioural risk factors for chronic disease and the quality of their measurement properties. It will allow recommendations on the most suitable and effective measures of these lifestyle behaviours using smartphones. Valid and reliable measurement of these behaviours and risk factor opens the door to targeted and real-time delivery of health behaviour interventions, providing unprecedented opportunities to offset the trajectory toward chronic disease. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42019122242.
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Comportamento Sedentário , Smartphone , Comportamentos Relacionados com a Saúde , Humanos , Estilo de Vida , Metanálise como Assunto , Reprodutibilidade dos Testes , Revisões Sistemáticas como AssuntoRESUMO
Cystic fibrosis (CF) is a lethal genetic disorder caused by mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Despite recent groundbreaking approval of genotype-specific small-molecule drugs, a significant portion of CF patients still lack effective therapeutic options that address the underlying cause of the disease. Through a phenotypic high-throughput screen of approximately 54,000 small molecules, we identified a novel class of CFTR modulators called amplifiers. The identified compound, the characteristics of which are represented here by PTI-CH, selectively increases the expression of immature CFTR protein across different CFTR mutations, including F508del-CFTR, by targeting the inefficiencies of early CFTR biosynthesis. PTI-CH also augments the activity of other CFTR modulators and was found to possess novel characteristics that distinguish it from CFTR potentiator and corrector moieties. The PTI-CH-mediated increase in F508del-CFTR did not elicit cytosolic or endoplasmic reticulum-associated cellular stress responses. Based on these data, amplifiers represent a promising new class of CFTR modulators for the treatment of CF that can be used synergistically with other CFTR modulators.
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Fibrose Cística/tratamento farmacológico , Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Bibliotecas de Moléculas Pequenas/farmacologia , Linhagem Celular , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/genética , Genótipo , Humanos , Mutação/genética , FenótipoRESUMO
In Neisseria meningitidis, iron-responsive gene regulation is mediated primarily by the ferric uptake regulator (Fur) protein. When complexed with iron, Fur represses gene expression by preventing transcription initiation. Fur can also indirectly activate gene expression via the repression of regulatory small RNAs (sRNA). One such Fur- and iron-regulated sRNA, NrrF, was previously identified in N. meningitidis and shown to repress expression of the sdhA and sdhC genes encoding subunits of the succinate dehydrogenase complex. In the majority of Gram-negative bacteria, sRNA-mediated regulation requires a cofactor RNA-binding protein (Hfq) for proper gene regulation and stabilization. In this study, we examined the role of Hfq in NrrF-mediated regulation of the succinate dehydrogenase genes in N. meningitidis and the effect of an hfq mutation on iron-responsive gene regulation more broadly. We first demonstrated that the stability of NrrF, as well as the regulation of sdhC and sdhA in vivo, was unaltered in the hfq mutant. Secondly, we established that iron-responsive gene regulation of the Fur-regulated sodB gene was dependent on Hfq. Finally, we demonstrated that in N. meningitidis, Hfq functions in a global manner to control expression of many ORFs and intergenic regions via iron-independent mechanisms. Collectively these studies demonstrate that in N. meningitidis, iron- and NrrF-mediated regulation of sdhC and sdhA can occur independently of Hfq, although Hfq functions more globally to control regulation of other N. meningitidis genes primarily by iron-independent mechanisms.