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2.
BMJ Open Gastroenterol ; 11(1)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38519047

RESUMO

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive therapeutic option to treat the sequelae of portal hypertension. It is unclear whether current international recommendations are reflected in current clinical practice across Australia and the extent of variations in care. This study aimed to address this gap in knowledge and benchmark the current landscape of TIPS services in Australia against international guidelines. METHODS: We designed a 42-item questionnaire according to practice-based recommendations and standards of international guidelines to investigate current landscape of TIPS service across four key domains: (1) service provision, (2) patient selection and indications, (3) best procedure practice, and (4) postoperative care. RESULTS: Gastroenterologist/hepatologists from 23 major liver centres (67.6%) across Australia currently performing TIPS completed the questionnaire. Between 2017 and 2020, there were 456 elective TIPS insertions. Units offering TIPS service had a low median number of TIPS insertions (n=7 per annum). More than half of respondents (56.5%) did not have institutional clinical practice protocols. There was marked variation in practices across institutions in terms of TIPS indications and patient selection. Despite variations, the success rate of elective TIPS was high at 91.7% (79-100%), with 86.6% (29-100%) for rescue TIPS. There was significant variation in postoperative follow-up and care. CONCLUSION: Current TIPS practice in Australia varies significantly across institutions. There is a need for a national consensus clinical practice guidelines to improve access and minimise unwarranted variation. A national registry for TIPS could measure, monitor, and report on quality of clinical care and patient outcomes.


Assuntos
Hipertensão Portal , Derivação Portossistêmica Transjugular Intra-Hepática , Humanos , Derivação Portossistêmica Transjugular Intra-Hepática/métodos , Hipertensão Portal/cirurgia , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Austrália/epidemiologia
3.
Gut Microbes ; 16(1): 2331520, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517357

RESUMO

Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.


Assuntos
Bacteriófagos , Microbioma Gastrointestinal , Humanos , Células CACO-2 , Bacteriófagos/fisiologia , Junções Íntimas , Colo
4.
PLoS One ; 18(11): e0289907, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37910527

RESUMO

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March-October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n = 12), secondary immunosuppression (N = 8) and those with primary or acquired immunodeficiency (i.e. HIV; N = 7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Austrália/epidemiologia
5.
BMC Gastroenterol ; 23(1): 356, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845625

RESUMO

OBJECTIVE: Delivering effective secondary preventive and integrated care has the potential to break the revolving-door phenomenon of frequent readmissions in patients with advanced chronic liver disease. To address this, we launched the Care Coordination of Liver Disease (CCoLD) pilot, a novel nurse-led cirrhosis clinic in Western Sydney. METHODS AND ANALYSIS: Following an index presentation to Blacktown or Mount Druitt hospitals (BMDH), patients (n = 89, matched by age, sex, and MELD-NA) were consecutively either followed up by the CCoLD clinical nurse consultant (intervention cohort) or received standard care (control cohort). Controlled evaluation of the impact of the nurse-led clinic was carried out for a 3-month period including readmission rates, survival, and cost effectiveness. RESULTS: The inaugural nurse-led clinic led to improvement in patient-level outcomes including a reduction in unplanned liver-related readmissions (2.08% for intervention cohort vs 12.2% for control cohort, p < 0.01), and mortality at 30 days (0% for intervention cohort vs 7.3% for control cohort, p = 0.03). Similar trends were observed at 90 days from index discharge. No deaths were observed in the intervention cohort as compared to the control cohort at 90 days (0% versus 7.3%, p = 0.03), while unplanned liver-related readmissions were 10.41% for the intervention cohort vs 19.5% for the control cohort (p = 0.115). Moreover, time to readmission was significantly longer in the intervention cohort, resulting in an overall cost-effective intervention. CONCLUSION: These findings highlight the significant impact of optimised care-coordination. A nurse-led clinic can deliver patient-centred, goal-directed, and cost-effective secondary prevention and care. A multicentre randomised trial for wider evaluation of these findings is warranted.


Assuntos
Papel do Profissional de Enfermagem , Readmissão do Paciente , Humanos , Cirrose Hepática/terapia , Alta do Paciente , Masculino , Feminino
6.
Int J Cardiol Cardiovasc Risk Prev ; 19: 200211, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37719420

RESUMO

Background: Obesity has been linked with alterations in hemodynamic, autonomic, and hormonal pathways in the body, leading to a spectrum of cardiovascular changes. We sought to evaluate the effects of obesity on structural and functional changes of the heart in the absence of cardiac disease and associated risk factors. Methods: We identified healthy outpatients without any cardiovascular disease or risk factors from our institution's echocardiography database (2017-2020). Patients were stratified by body mass index (BMI; normal: 18.5-25 kg/m2; overweight: 25-30 kg/m2; class 1 obesity: 30-35 kg/m2; class 2 obesity: 35-40 kg/m2; class 3 obesity: >40 kg/m2). Traditional and advanced echocardiographic parameters of cardiac chamber size and function including left ventricular global longitudinal strain (LV-GLS), left atrial reservoir strain (LASr), and right ventricular free wall strain (RV-FWS) were examined. The optimal cut-off BMI for discriminating LV-GLS (>-17.5%), LASr (<23%), and RV-FWS (>-23%) impairment was calculated using ROC curves. Results: 307 patients were assessed (41.5 ± 13.3yrs; 36.5%male; LVEF 61.3 ± 4.8%). No significant differences in indexed chamber volumes or LVEF were appreciated across BMI groups (p > 0.05 for all). LV-GLS, LASr, and RV-FWS were all significant on one-way ANOVA for differences from the group mean (all p < 0.01). Jonckheere-Terpstra test confirmed a significant trend of lower absolute LV-GLS, LASr and RV-FWS values across the rising BMI groups. On ROC curve analysis, a BMI value of 29.9 kg/m2, 35.1 kg/m2, and 37.3 kg/m2 were associated with LASr (AUC: 0.75), RV-FWS (AUC: 0.72), and LV-GLS (AUC: 0.75) impairment respectively. Conclusion: Obesity is linked with subclinical reduction of cardiac function in otherwise healthy subjects without cardiovascular risk factors, with reduction of left atrial function occurring at lower BMI, followed by the right and left ventricular function.

8.
Int J Health Plann Manage ; 38(5): 1228-1249, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37469119

RESUMO

BACKGROUND: One of the most difficult challenges in healthcare involves equitable allocation of resources. Our review aimed to identify international funding models in Organisation for Economic Co-operation and Development (OECD) countries for government-funded public hospitals and evidence underpinning their efficacy, via review of the peer-reviewed and grey literature. METHODS: Ovid-Medline, Ovid Embase, Scopus, and PubMed were searched for peer-reviewed literature. Advanced Google searches and targeted hand searches of relevant organisational websites identified grey literature. Inclusion criteria were: English language, published between 2011 and 2022, and that the article: (1) focused on healthcare funding; (2) reported on or identified specific factors, indexes, algorithms or formulae associated with healthcare funding; and (3) referred to countries that are members of the OECD, excluding the United States (US). RESULTS: For peer-reviewed literature 1189 abstracts and 35 full-texts were reviewed; six articles met the inclusion criteria. For grey literature, 2996 titles or abstracts and 37 full-texts were reviewed; five articles met the inclusion criteria. Healthcare funding arrangements employed in 15 OECD countries (Australia, Belgium, Canada, Finland, France, Germany, Israel, Italy, the Netherlands, New Zealand, Norway, Spain, Sweden, Switzerland, and the United Kingdom [UK; specifically, England, Scotland, Wales and Northern Ireland]) were identified, but papers reported population-based funding arrangements for specific regions rather than hospital-specific models. CONCLUSIONS: While some models adjusted for deprivation and ethnicity factors, none of the identified documents reported on health systems that adjusted funding allocation for social determinants such as health literacy levels.


Assuntos
Serviços de Saúde , Organização para a Cooperação e Desenvolvimento Econômico , Estados Unidos , Reino Unido , Atenção à Saúde , Hospitais Públicos
9.
Methods Protoc ; 6(2)2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-37104017

RESUMO

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

10.
Hepatol Int ; 17(3): 542-545, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36971983

RESUMO

The perception of high surgical risk among patients with cirrhosis has resulted in a long-standing reluctance to operate. Risk stratification tools, first implemented over 60 years ago, have attempted to assess mortality risk among cirrhotic patients and ensure the best possible outcomes for this difficult to treat cohort. Existing postoperative risk prediction tools including the Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) provide some prediction of risk in counselling patients and their families but tend to overestimate surgical risk. More personalised prediction algorithms such as the Mayo Risk Score and VOCAL-Penn score that incorporate surgery-specific risks have demonstrated a significant improvement in prognostication and can ultimately aid multidisciplinary team determination of potential risks. The development of future risk scores will need to incorporate, first and foremost, predictive efficacy, but perhaps just as important is the feasibility and usability by front-line healthcare professionals to ensure timely and efficient prediction of risk for cirrhotic patients.


Assuntos
Doença Hepática Terminal , Humanos , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Fibrose , Fatores de Risco , Prognóstico , Estudos Retrospectivos
12.
Endoscopy ; 55(7): 611-619, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36716781

RESUMO

INTRODUCTION: The frequency and severity of abdominal pain after endoscopic mucosal resection (EMR) of colonic laterally spreading lesions (LSLs) of ≥ 20 mm is unknown, as are the risk factors to predict its occurrence. We aimed to prospectively characterize pain after colonic EMR , determine the rapidity and frequency of its resolution after analgesia, and estimate the frequency of needing further intervention. METHODS: Procedural and lesion data on consecutive patients with LSLs who underwent EMR at a single tertiary referral center were prospectively collected. If pain after colonic EMR, graded using a visual analogue scale (VAS), lasted > 5 minutes, 1 g of paracetamol was administered. Pain lasting > 30 minutes lead to clinical review and upgrade to opiate analgesics. Investigations and interventions for pain were recorded. RESULTS: 67/336 patients (19.9 %, 95 %CI 16.0 %-24.5 %) experienced pain after colonic EMR (median VAS 5, interquartile range 3-7). Multivariable predictors of pain were: lesion size ≥ 40 mm, odds ratio [OR] 2.15 (95 %CI 1.22-3.80); female sex, OR 1.99 (95 %CI 1.14-3.48); and intraprocedural bleeding requiring endoscopic control, OR 1.77 (95 %CI 0.99-3.16). Of 67 patients with pain, 51 (76.1 %, 95 %CI 64.7 %-84.7 %) had resolution of their "mild pain" after paracetamol and were discharged without sequelae. The remaining 16 (23.9 %) required opiate analgesia (fentanyl), after which 11/16 patients (68.8 %; "moderate pain") could be discharged. The 5/67 patients (7.5 %) with "severe pain" had no resolution despite fentanyl; all settled during hospital admission (median duration 2 days), intravenous analgesia, and antibiotics. CONCLUSION: Pain after colonic EMR occurs in approximately 20 % of patients and resolves rapidly and completely in the majority with administration of intravenous paracetamol. Pain despite opiates heralds a more serious scenario and further investigation should be considered.


Assuntos
Acetaminofen , Ressecção Endoscópica de Mucosa , Humanos , Feminino , Acetaminofen/efeitos adversos , Ressecção Endoscópica de Mucosa/efeitos adversos , Alta do Paciente , Dor/etiologia , Fentanila/efeitos adversos , Colonoscopia/efeitos adversos
13.
Immunol Cell Biol ; 101(2): 142-155, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36353774

RESUMO

The long-term health consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are still being understood. The molecular and phenotypic properties of SARS-CoV-2 antigen-specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen-specific memory B-cell (MBC) population has not yet been analyzed to the same degree, but phenotypic analysis suggests differences following recovery from mild or severe coronavirus disease 2019 (COVID-19). Here, we performed single-cell molecular analysis of the SARS-CoV-2 receptor-binding domain (RBD)-specific MBC population in three patients after severe COVID-19 and four patients after mild/moderate COVID-19. We analyzed the transcriptomic and B-cell receptor repertoire profiles at ~2 months and ~4 months after symptom onset. Transcriptomic analysis revealed a higher level of tumor necrosis factor-alpha (TNF-α) signaling via nuclear factor-kappa B in the severe group, involving CD80, FOS, CD83 and TNFAIP3 genes that was maintained over time. We demonstrated the presence of two distinct activated MBCs subsets based on expression of CD80hi TNFAIP3hi and CD11chi CD95hi at the transcriptome level. Both groups revealed an increase in somatic hypermutation over time, indicating progressive evolution of humoral memory. This study revealed distinct molecular signatures of long-term RBD-specific MBCs in convalescence, indicating that the longevity of these cells may differ depending on acute COVID-19 severity.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Células B de Memória , Convalescença , Anticorpos Antivirais
14.
Cells ; 11(18)2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36139388

RESUMO

Numerous cell sources are being explored to replenish functional ß-cell mass since the proof-of -concept for cell therapy of diabetes was laid down by transplantation of islets. Many of these cell sources have been shown to possess a degree of plasticity permitting differentiation along new lineages into insulin-secreting ß-cells. In this review, we explore emerging reprograming pathways that aim to generate bone fide insulin producing cells. We focus on small molecules and key transcriptional regulators that orchestrate phenotypic conversion and maintenance of engineered cells.


Assuntos
Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Insulinas , Diferenciação Celular , Terapia Baseada em Transplante de Células e Tecidos , Diabetes Mellitus Tipo 1/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Insulinas/metabolismo
15.
Hepatol Commun ; 6(11): 3260-3271, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36153817

RESUMO

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Técnica Delfos , Indicadores de Qualidade em Assistência à Saúde , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Antivirais
16.
BMC Psychiatry ; 22(1): 517, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35907801

RESUMO

BACKGROUND: Previous research on the psychological mechanisms of obesity has primarily focused on acute psychopathology. However, there is limited literature on the role of more complex and entrenched psychological processes in weight management. The current study aimed to expand previous research by examining more enduring psychological constructs, including early maladaptive schemas (EMS), schemas modes, and trauma. METHODS: Participants (N = 125) comprised adults with normal weight (n = 40) and obesity (n = 85) from community and clinical settings in Australia. Eligible participants completed a series of self-report questionnaires via Research Electronic Data Capture (REDCap). Two, separate, one-way multivariate analysis of variance (MANOVA) were conducted to examine group differences on the outcome variables. RESULTS: Findings indicated a significant effect of group on EMS and schema modes, V = .51, F(32, 92) = 2.97, p < .001, partial η2 = .51. Follow-up univariate tests revealed that individuals with obesity endorsed significantly more maladaptive schemas and schema modes and significantly less healthy schema modes than individuals with normal weight. In addition, results demonstrated a significant effect of group on childhood trauma and posttraumatic stress disorder (PTSD) symptoms, V = .19, F(6, 118) = 4.70, p < .001, partial η2 = .19. Subsequent univariate tests and chi-square analyses indicated that individuals with obesity reported significantly more childhood trauma as well as significantly more PTSD symptoms within the last month than normal weight individuals. CONCLUSION: This was the first study to compare EMS and schema modes in treatment-seeking individuals with obesity and normal weight controls using the short form version 3 of the Young Schema Questionnaire and revised, 118-item, Schema Mode Inventory. Overall, findings revealed that individuals with obesity experience more complex and enduring psychological difficulties than normal weight individuals. Increased assessment and targeted treatment of these underlying mental health concerns may contribute to a more holistic conceptualisation of obesity and could improve the long-term success of weight management.


Assuntos
Experiências Adversas da Infância , Transtornos de Estresse Pós-Traumáticos , Adaptação Psicológica , Adulto , Humanos , Obesidade , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e Questionários
17.
J Eat Disord ; 10(1): 82, 2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710487

RESUMO

BACKGROUND: Despite being the first validated measure of grazing, the Grazing Questionnaire (GQ) has not been investigated among individuals with obesity. Therefore, the current study aimed to examine the psychometric properties of the GQ in an obesity sample. METHODS: Participants (N = 259) were recruited from community and clinical settings in Australia. The sample comprised adults with normal weight (n = 77) and obesity (n = 182). A portion of individuals with obesity (n = 102) had binge eating disorder (BED). Data from the obesity group was examined to establish the factor structure, validity, and reliability of the GQ. A one-way ANOVA with planned contrasts was conducted to compare scores on the GQ across groups. RESULTS: Confirmatory factor analysis revealed that the 2-factor model of the GQ was the best model fit for individuals with obesity. The GQ demonstrated high internal consistency, test-retest reliability over 3 months, and convergent and divergent validity. As hypothesised, the obesity group had significantly higher scores on the GQ than the normal weight group, while the obesity with BED group had significantly higher scores than the obesity without BED group. CONCLUSION: This was the first study to investigate the psychometric properties of the GQ in an obesity sample. Overall, findings indicated that the GQ is a psychometrically sound measure of grazing among individuals with obesity. These findings provide further support for two distinct subtypes of grazing and highlight the importance of increased assessment and management of grazing behaviours for individuals with obesity and eating disorders. Maintaining a healthy weight is one of the greatest challenges for individuals with obesity. Certain eating patterns such as grazing may contribute to difficulties in weight management. Grazing is the repetitive and unplanned eating of small amounts of food that is not related to feeling hungry. Researchers and clinicians often use self-report questionnaires to measure grazing. However, the first validated questionnaire of grazing has not been investigated among individuals with obesity. Therefore, the goal of this study was to examine and validate the Grazing Questionnaire in individuals with obesity. Overall, our results showed that the Grazing Questionnaire is a valid and reliable self-report measure of grazing in individuals with obesity. Similar to previous research, we found that there are two subtypes of grazing. The first subtype involves continuous, unplanned eating. The second subtype is associated with a sense of loss of control over eating. We also found that people with obesity and binge eating disorder graze more than people with obesity that do not have binge eating disorder, while both groups graze more than individuals with normal weight. We recommend that clinicians routinely assess and treat unhelpful grazing patterns when working with individuals with obesity and eating disorders.

18.
Cell Rep ; 38(6): 110345, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35090598

RESUMO

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%-76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection.


Assuntos
Anticorpos Amplamente Neutralizantes/metabolismo , Células B de Memória/metabolismo , SARS-CoV-2/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Austrália , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , COVID-19/imunologia , Estudos de Coortes , Feminino , Humanos , Imunidade/imunologia , Imunidade Humoral/imunologia , Masculino , Células B de Memória/imunologia , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/imunologia
19.
Inflamm Bowel Dis ; 28(4): 586-598, 2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-34724042

RESUMO

BACKGROUND: Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans. METHODS: Human intestinal biopsies were collected from Crohn's disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score. RESULTS: A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P < .0001) and unaffected CD (P < .0001), with transitional CD specimens also showing greater staining than controls (P < .05) and unaffected CD (P < .05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P < .0001) and unaffected CD (P < .0001) and was significantly higher in transitional CD than in controls (P < .0001) and unaffected CD (P < .0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P < .05), unaffected CD (P < .0001) and transitional CD (P < .05), with transitional CD specimens showing greater staining than unaffected CD (P < .01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment. CONCLUSION: These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.


Our data show for the first time that the density of neutrophil extracellular trap formed in the bowel of Crohn's disease patients increases with increasing disease severity, suggesting that myeloperoxidase-mediated host-tissue damage may play a role in disease pathogenesis.


Assuntos
Doença de Crohn , Armadilhas Extracelulares , Doença de Crohn/patologia , Armadilhas Extracelulares/metabolismo , Histonas , Humanos , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Peroxidase/metabolismo
20.
Nutrients ; 13(11)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34836331

RESUMO

Australia has one of the highest prevalences of obesity in the developed world with recognised gaps in patient access to obesity services. This non-randomised before and after study investigated the health benefits and patient acceptability of integrating the Get Healthy Service, a state-funded telephone-delivered coaching service in Australia, as an adjunct to multidisciplinary care for adults attending a public obesity service. Forty-one participants received multidisciplinary care alone while 39 participants were subsequently allocated to receive adjunctive treatment with the Get Healthy Service. Weight, body mass index, glycosylated haemoglobin, measurement of hepatic steatosis and liver enzymes were collected at baseline and 6 months. Participant evaluation was obtained post intervention. Statistically significant reductions from baseline were achieved for both control and intervention with respect to weight (-6.7 ± 2.2 kg, p = 0.01; -12.6 ± 3.2, p = 0.002), body mass index (-2.3 ± 0.8, p = 0.01; -4.8 ± 1.2 kg/m2, p = 0.002) and glycosylated haemoglobin (-0.2 ± 0.2%, p = 0.2 (NS); -0.7 ± 0.2%, p = 0.02), respectively. There were no significant differences in steatosis or liver enzymes or in outcomes between control and intervention cohorts. A high level of patient acceptability was reported. Integrating telephone-delivered coaching provided non-inferior care and high levels of patient satisfaction. Telephone coaching aligned with the principles of an obesity service should be trialled to improve patient access to obesity interventions.


Assuntos
Dieta Saudável/métodos , Tutoria/métodos , Obesidade/terapia , Telemedicina/métodos , Programas de Redução de Peso/métodos , Adolescente , Adulto , Austrália , Índice de Massa Corporal , Estudos Controlados Antes e Depois , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Obesidade/fisiopatologia , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Telefone , Resultado do Tratamento , Redução de Peso , Adulto Jovem
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