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INTRODUCTION: Effective and safe vaccines against COVID-19 are essential to achieve global control of the coronavirus (SARS-CoV-2). Using faith centres may offer a promising route for promoting higher vaccine uptake from certain minority ethnic groups known to be more likely to be vaccine hesitant. METHODS: This cross-sectional study explored attendees' perceptions, experiences of being offered, and receiving COVID-19 vaccination in a local mosque in Woking, Surrey, UK. About 199 attendees completed a brief questionnaire on experiences, views, motivations about attending the mosque and vaccination on site. RESULTS: The most common ethnic groups reported were White British (39.2%) and Pakistani (22.6%); 36.2% identified as Christian, 23.6% as Muslim, 5.5% as Hindu, and 17.1% had no religion. Genders was relatively equal with 90 men (45.2%) and 98 women (49.2%), and 35-44-year-olds represented the most common age group (28.1%). Views and experiences around receiving vaccinations at the mosque were predominantly positive. Primary reasons for getting vaccinated at the mosque included convenience, accessibility, positive aspects of the venue's intercultural relations, and intentions to protect oneself against COVID-19, regardless of venue type. Negative views and experiences in regards to receiving the vaccination at the mosque were less common (7% expressed no intention of recommending the centre to others), and disliked aspects mostly referred to the travel distance and long waiting times. CONCLUSIONS: Offering COVID-19 vaccination in faith centres appears acceptable for different faith groups, ensuring convenient access for communities from all religions and ethnic backgrounds.
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BACKGROUND & AIMS: Prevention of neurological worsening (NW) under therapy is an unmet need in the management of Wilson disease (WD). In this study, we aimed to characterize the occurrence, associated outcomes and potential reversibility of NW in WD. METHODS: From a total cohort of 457 patients with WD, 128 patients with WD and neurological features at any time point (all Caucasian, 63 females, median age at diagnosis 22 years) were identified by chart review at University Hospital Heidelberg and grouped according to initial presentation. The timing and occurrence of NW was assessed following a structured clinical examination during clinical visits. RESULTS: Early NW (within the first 3 months of therapy) was observed in 30 out of 115 (26.1%) patients with neurological or mixed presentation and never in patients with a purely hepatic or asymptomatic presentation (0%). Late NW (after >12 months) was seen in a further 23 (20%) with neurological or mixed presentation and in 13 out of 294 (4.4%) patients with a hepatic or asymptomatic presentation. The median time from start of treatment to late NW was 20 months. Only three patients experienced NW between 3 and 12 months. NW was observed with D-penicillamine, trientine and zinc therapy and was reversible in 15/30 (50%) with early NW and in 29/36 (81%) with late NW. CONCLUSIONS: In this study, we identified two peaks in NW: an early (≤3 months) treatment-associated peak and a late (>12 months of treatment) adherence-associated peak. Early paradoxical NW was attributed to treatment initiation and pre-existing neurological damage, and was not observed in those with a hepatic or asymptomatic presentation. Late NW is likely to be associated with non-adherence. IMPACT AND IMPLICATIONS: In patients with Wilson disease, defined as an excess accumulation of copper which can damage the liver, brain and other vital organs, neurological worsening can occur despite chelation therapy. The study identifies different patterns of 'early' (<3 months) vs. 'late' (>12 months) neurological worsening in relation to initiation of chelation therapy and establishes possible causes and the potential for reversibility. These data should be useful for counseling patients and for guiding the optimal management of chelation therapy.
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Degeneración Hepatolenticular , Femenino , Humanos , Degeneración Hepatolenticular/complicaciones , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/tratamiento farmacológico , Penicilamina/uso terapéutico , Penicilamina/efectos adversos , Trientina , Zinc/uso terapéutico , CobreRESUMEN
BACKGROUND & AIMS: The risk of significant liver fibrosis from prolonged methotrexate (MTX) exposure has been estimated at around 5%, prompting intensive monitoring strategies. However, the evidence is derived from retrospective studies that under-reported risk factors for liver disease. We evaluated the risk of long-term MTX therapy on liver fibrosis in a longitudinal cohort study using two non-invasive markers. METHOD: Between 2014-2021, adult patients diagnosed with rheumatoid arthritis (RA) or psoriasis for ≥2 years were recruited prospectively from six UK sites. The MTX group included patients who received MTX for ≥6 months, whereas the unexposed group included those who never received MTX. All patients underwent full liver profiling, with transient elastography (TE) and enhanced liver fibrosis (ELF) marker measurements. RESULTS: A total of 999 patients (mean age 60.8 ± 12 years, 62.3% females) were included. Of 976 with valid TE values, 149 (15.3%) had liver stiffness ≥7.9 kPa. Of 892 with a valid ELF, 262 (29.4%) had ELF ≥9.8. Age and BMI were independently associated with elevated liver stiffness and ELF. Neither MTX cumulative dose nor duration was associated with elevated liver stiffness. Diabetes was the most significant risk factor associated with liver stiffness ≥7.9 kPa (adjusted odds ratio = 3.19; 95% CI 1.95-5.20; p <0.001). Regular use of non-steroidal anti-inflammatory drugs showed the strongest association with ELF ≥9.8 (odds ratio = 1.76; 95% CI 1.20-2.56; p = 0.003), suggesting the degree of joint inflammation in RA may confound ELF as a non-invasive marker of liver fibrosis. CONCLUSION: The risk of liver fibrosis attributed to MTX itself might have been previously overestimated; there is a need to consider modifying current monitoring guidelines for MTX. IMPACT AND IMPLICATIONS: Current guidelines recommend intensive (2-3 monthly) monitoring strategies for patients on long-term methotrexate therapy due to the potential risk of liver fibrosis. Evaluation of the association using two validated non-invasive markers of liver fibrosis, liver stiffness and enhanced liver fibrosis score, in a large cohort of patients with rheumatoid arthritis or psoriasis shows that the reported risk has previously been overestimated. The clinical focus should be to improve patients' metabolic risk factors, diabetes and BMI, that are independently associated with liver stiffness. There is a need to consider modifying current treatment monitoring guidelines for methotrexate.
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Artritis Reumatoide , Psoriasis , Adulto , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Metotrexato/efectos adversos , Estudios Retrospectivos , Estudios Longitudinales , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/epidemiología , Cirrosis Hepática/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamenteRESUMEN
BACKGROUND AND AIMS: Although a good genotype-phenotype correlation has not been established in Wilson disease (WD), patients with loss-of-function (LOF) ATP7B variants demonstrate different clinical and biochemical characteristics. We aim to describe long-term treatment outcomes in the chronic liver disease (CLD) phenotype and evaluate an association with LOF variants. METHODS: This was a single-center retrospective review of WD patients with at least 1 variant in ATP7B. Demographic, biochemical, genetic, and clinical parameters were obtained. The composite clinical endpoint of liver transplantation or death was used for probands with CLD phenotype on chelators. RESULTS: Of 117 patients with hepatic WD: 71 had CLD, 27 had fulminant hepatic failure requiring urgent liver transplantation, and 19 were diagnosed through family screening. Median age at diagnosis was 13.1 (interquartile range, 9.7-17.6) years. In total, 91 variants in ATP7B were identified in the study population. At least 1 LOF variant was present in 60 (51.3%) patients. During median follow-up of 10.7 (interquartile range, 6.7-18.9) years, 10 (14.1%) of the probands with CLD reached the composite endpoint. There was a worse transplant-free survival for patients prescribed chelation therapy in patients with at least 1 LOF variant (P = .03). CONCLUSIONS: Patients with WD and CLD phenotype on chelators, who have at least 1 LOF variant in ATP7B, have a worse prognosis during long-term follow up. This subgroup of patients requires close monitoring for signs of progressive liver disease. Sequencing of ATP7B may be used in the diagnosis of WD, and in addition, it may provide useful prognostic information for patients with hepatic WD.
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Degeneración Hepatolenticular , Humanos , Quelantes , Genotipo , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/tratamiento farmacológico , Mutación , Fenotipo , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Wilson's disease (WD) is an autosomal-recessive disorder caused by ATP7B gene mutations leading to pathological accumulation of copper in the liver and brain. Adoption of initial treatments for WD was based on empirical observations. These therapies are effective, but there are still unmet needs for which treatment modalities are being developed. An increase of therapeutical trials is anticipated. APPROACH AND RESULTS: The first Wilson Disease Aarhus Symposium (May 2019) included a workshop on randomized clinical trial design. The authors of the article were organizers or presented during this workshop, and this article presents their consensus on the design of clinical trials for WD, addressing trial population, treatment comparators, inclusion and exclusion criteria, and treatment endpoints. To achieve adequate recruitment of patients with this rare disorder, the study groups should include all clinical phenotypes and treatment-experienced as well as treatment-naïve patients. CONCLUSIONS: The primary study endpoint should be clinical or a composite endpoint until appropriate surrogate endpoints are validated. Standardization of clinical trials will permit pooling of data and allow for better treatment comparisons, as well as reduce the future numbers of patients needed per trial.
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Degeneración Hepatolenticular/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Adolescente , Biomarcadores , Niño , Progresión de la Enfermedad , Educación , Degeneración Hepatolenticular/genética , Degeneración Hepatolenticular/patología , Humanos , Resultado del Tratamiento , Adulto JovenRESUMEN
Wilson's disease (WD) is a rare cause of acute liver failure (ALF) that is thought to have a uniformly fatal outcome without liver transplantation (LT). Previous studies proposed diagnostic and prognostic criteria for WD-ALF. It is not known whether these apply to WD patients presenting as severe acute liver injury (ALI) without encephalopathy. From 2008 to 2018, 822 patients with ALI in the US Acute Liver Failure Study Group (ALFSG) registry were enrolled and prospectively followed. The diagnosis of WD-ALI was confirmed in 8 patients. Serum biochemical diagnostic ratios predicting WD-ALF (alkaline phosphatase [ALP]:total bilirubin(TB) and aspartate aminotransferase [AST]:alanine aminotransferase [ALT]) were determined in these patients, and predictors of prognosis for WD-ALI were evaluated. Of these 8 ALI-WD patients, 5 received an LT. Ratios of both ALP:TB of <4 and AST:ALT of >2.2 on study admission were met in 4 LT patients. All LT patients were female. The Model for End-Stage Liver Disease scores on admission were generally higher in LT patients. All transplanted patients had an initial revised WD score of >11 (>10 predicting poor outcome without LT in WD-ALF), whereas in non-LT patients, 2 had scores of 9, and 1 a score of 13. Also, 3 LT patients were started on chelation therapy, 2 were started on plasmapheresis, and 1 was started on Molecular Adsorbent Recirculating System therapy. All non-LT patients were treated with chelation. At 21 days, all patients were alive and discharged from the hospital. In conclusion, some patients with ALI due to WD may survive without LT. Revised Wilson index scores >10 predict poor outcome in most patients with WD-ALI, as they do for WD-ALF, and they correlate positively with the ALI model in this cohort. Biochemical ratios for WD diagnosis appear more applicable to ALF compared with WD-ALI.
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Enfermedad Hepática en Estado Terminal , Degeneración Hepatolenticular , Trasplante de Hígado , Adulto , Femenino , Degeneración Hepatolenticular/complicaciones , Degeneración Hepatolenticular/diagnóstico , Degeneración Hepatolenticular/terapia , Humanos , Índice de Severidad de la EnfermedadRESUMEN
Hepatitis B virus (HBV) infection is estimated to affect 292 million people worldwide, 90% of them are unaware of their HBV status. The Determine HBsAg 2 (Alere Medical Co, Ltd Chiba Japan [Now Abbott]) is a rapid test that meets European Union (EU) regulatory requirements for Hepatitis B surface antigen 2 (HBsAg) analytical sensitivity, detecting the 0.1 IU/mL World Health Organization (WHO) International HBsAg Standard. This prospective, multicentre study was conducted to establish its clinical performance. 351 evaluable subjects were enrolled, 145 HBsAg-positive. The fingerstick whole blood sensitivity and specificity were 97.2% and 98.5% (15' reading, reference assay cut-off 0.05 IU/mL), sensitivity increasing to 97.9% with the prespecified cut-off 0.13 IU/mL (EU regulations). The venous whole blood, serum and plasma sensitivity was 97.2%, 97.9%, and 98.6%, respectively (15' reading); reaching 99%, 99.5% and 100% specificity. A testing algorithm following up an initial positive fingerstick test result with plasma/serum test demonstrates 100% specificity. The Determine HBsAg 2 test gives 15-minute results with high sensitivity and specificity, making it an ideal tool for point-of-care testing, with the potential to enable large-scale population-wide screening to reach the WHO HBV diagnostic targets. The evaluated test improves the existing methods as most of the reviewed rapid tests do not meet the EU regulatory requirements of sensitivity.
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INTRODUCTION: PBC registries in the UK focus on data from secondary care without clear coordinated contribution from primary care. The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) receives data from > 500 primary care practices (PCPs). Notably, the Lancet commissioning group is extracting data from the RCGP RSC database to shape UK policy on liver disease. AIMS: To create a novel ontology to facilitate PBC case finding from primary care provider (PCP) records. METHODS: RCGP RSC data were collected from participating PCPs in the county of Surrey, UK. PBC diagnostic criteria of the AASLD and EASL guidelines were used to develop 725 data codes to facilitate patient record searches. A scoring system built into the ontology allowed categorization of cases as PBC definite, PBC probable, and PBC unlikely. RESULTS: A total of 218,099 records were searched from participating PCPs. Of these, there were 58 PBC definite, 2317 PBC probable, and 215,724 PBC unlikely patients. There were 32 PBC definite patients who did not match to our regional PBC database and were henceforth included as new-found cases. Two of these cases were not labeled as PBC by the PCP. From the PBC unlikely group, 7/215,724 (0.003%) patients were labeled as PBC in secondary care records; however, none of them were coded as having PBC by their PCPs. CONCLUSIONS: Utilization of the UK National RCGP RSC database supported by novel ontology score has successfully helped us identify (i) new cases of PBC not known to local/regional secondary care providers and (ii) de novo PBC cases. There are many PBC probable cases whose data merit further careful evaluation.
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Colangitis/epidemiología , Atención Primaria de Salud , Atención Secundaria de Salud , Áreas de Influencia de Salud , Colangitis/terapia , Estudios de Factibilidad , Humanos , Sistema de Registros , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases. METHODS: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology. RESULTS: Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82-100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy. CONCLUSION: These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia.
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Agammaglobulinemia/inducido químicamente , Enfermedades Autoinmunes/tratamiento farmacológico , Linfocitos B , Inmunización Pasiva/efectos adversos , Enfermedades Reumáticas/tratamiento farmacológico , Adulto , Comités Consultivos , Agammaglobulinemia/inmunología , Enfermedades Autoinmunes/inmunología , Toma de Decisiones Clínicas , Técnica Delphi , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/inmunologíaAsunto(s)
Hepatopatías , Humanos , Hepatopatías/diagnóstico , Hepatopatías/patología , Enfermedad CrónicaRESUMEN
BACKGROUND: Screening programmes are well established in cancer, and are now being implemented in other conditions. An effective screening programme leads to early disease detection and improved outcomes but its impact is dependent on the quality of the test and the proportion of the target population participating. A further consideration is that uptake of screening by minority groups is low. PURPOSE: To determine which interventions have successfully increased screening uptake amongst minorities. DATA SOURCES: Medline, Cochrane database and the grey literature were searched from 1990 to 1st March 2016. STUDY SELECTION: Fifty-five English language studies that assessed uptake of screening in any minority population in the country of study aged over 18 years and that included a comparison arm. DATA EXTRACTION: Independent data extraction was undertaken by two researchers (CK and MP), using a predesigned data extraction form (DEF) which assisted retrieval of the core contents of each study and the organisation of material. DATA SYNTHESIS: Evidence was organised by screening test and type of intervention. Two authors (CK and MP) extracted data into evidence tables to enable comparison of study characteristics and findings. The heterogeneity of methods precluded a meta-analysis thus results are descriptive. Evidence was also assessed, using the Cochrane Collaboration risk of bias tables. RESULTS: This systematic review appraises data from international studies on a variety of minority groups, interventions and screening programmes providing a narrative review of their success and limitations.
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BACKGROUND: Wilson disease requires lifelong therapy, currently given daily in multiple divided dosages. AIM: To prospectively evaluate once-daily trientine as therapy for Wilson disease. STUDY GROUP: eight patients (seven males) aged 22-71 years with stable Wilson disease treated from 4 to 50 years. Patients were monitored for 3 months then for 12 months on a single daily dose of trientine (15 mg/kg). RESULTS: All patients remained clinically well. ALT and AST fluctuated in some, but none required treatment stoppages or side effects. Liver synthetic function was unchanged. Mean 24-h urine copper and zinc excretions at end of treatment were 313.4 ± 191.7 and 2,214 ± 1,346 µg, respectively. CONCLUSIONS: Once-daily trientine should be explored further for possible maintenance therapy for WD. Single daily dose may improve adherence to therapy. Larger trials and longer-term follow-up will establish the safety and treatment efficacy of this once-daily treatment regimen for WD (registration: NCT01472874).
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Quelantes/administración & dosificación , Degeneración Hepatolenticular/tratamiento farmacológico , Trientina/administración & dosificación , Administración Oral , Adulto , Anciano , Quelantes/efectos adversos , Esquema de Medicación , Femenino , Degeneración Hepatolenticular/diagnóstico , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Pacientes Desistentes del Tratamiento , Satisfacción del Paciente , Proyectos Piloto , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Trientina/efectos adversos , Adulto JovenRESUMEN
Research ethics committees exist internationally to review research proposals to protect the rights and safety of human participants and researchers involved in research. These committees recruit a panel of expert and lay members, mostly on an unpaid voluntary basis, with relevant scientific experience to appraise these studies. Contemporary data in the UK show that women and people over 55 years old are overrepresented in these committee panels in the Health Research Authority, suggesting that there are potential barriers to inclusivity and participation. A variety of global approaches to tackle these barriers include targeting specific populations, such as faith or community leaders, or implementing quotas have been adopted. Further research is needed to understand likely barriers preventing participation in research ethics committees in the UK and how they may be overcome.
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Comités de Ética en Investigación , Humanos , Femenino , Persona de Mediana Edad , Reino UnidoRESUMEN
Background & Aims: Wilson disease (WD) is caused by accumulation of copper primarily in the liver and brain. During maintenance therapy of WD with D-penicillamine, current guidelines recommend on-treatment ranges of urinary copper excretion (UCE) of 200-500 µg/24 h and serum non-ceruloplasmin-bound copper (NCC) of 50-150 µg/L. We compared NCC (measured by two novel assays) and UCE from patients with clinically stable WD on D-penicillamine therapy with these recommendations. Methods: This is a secondary analysis of data from the Chelate trial (NCT03539952) that enrolled physician-selected patients with clinically stable WD on D-penicillamine maintenance therapy (at an unaltered dose for at least 4 months). We analyzed laboratory samples from the first screening visit, prior to interventions. NCC was measured by either protein speciation (NCC-Sp) using anion exchange high-performance liquid chromatography protein speciation followed by copper determination with inductively coupled plasma mass spectroscopy or as exchangeable copper (NCC-Ex). NCC-Sp was also analyzed in healthy controls (n = 75). Results: In 76 patients with WD with 21.3±14.3 average treatment-years, NCC-Sp (mean±SD: 56.6±26.2 µg/L) and NCC-Ex (mean±SD: 57.9±24.7 µg/L) were within the 50-150 µg/L target in 61% and 54% of patients, respectively. In addition, 36% and 31%, respectively, were even below the normal ranges (NCC-Sp: 46-213 µg/L, NCC-Ex: 41-71 µg/L). NCC-Ex positively correlated with NCC-Sp (r2 = 0.66, p <0.001) but with systematic deviation. UCE was outside the 200-500 µg/24 h target range in 58%. Only 14/69 (20%) fulfilled both the NCC-Sp and UCE targets. Clinical or biochemical signs of copper deficiency were not detected. Conclusion: Clinically stable patients with WD on maintenance D-penicillamine therapy frequently have lower NCC-Sp or higher UCE than current recommendations without signs of overtreatment. Further studies are warranted to identify appropriate target ranges of NCC-Sp, NCC-Ex and UCE in treated WD. Impact and implications: Chelator treatment of patients with Wilson disease (WD) is currently guided by measurements of non-ceruloplasmin-bound copper (NCC) and 24 h urinary copper excretion (UCE) but validation is limited. In 76 adults with ≈21 years history of treated WD and clinically stable disease on D-penicillamine therapy, NCC was commonly found to be below normal values and recommended target ranges whether measured by protein speciation (NCC-Sp) or as exchangeable copper (NCC-Ex), while UCE values were above the recommended target range in 49%. Common wisdom would suggest overtreatment in these cases, but no clinical or biochemical signs of copper deficiency were observed. Exploratory analysis of liver enzymes suggested that NCC below levels seen in controls may be beneficial, while the relation to UCE was less clear. The data calls for critical re-evaluation of target ranges for treatment of WD, specific for drug and laboratory methodology. Clinical trial number: (NCT03539952).
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BACKGROUND: Enhanced cell expression of MAdCAM-1 is critical in tissue recruitment of lymphocytes in response to stimuli expressing the α4ß7 integrin. MAdCAM-1 is well characterized in gut mucosa with emerging evidence of hepatic expression. AIMS: (i) Compare quantitative/semi-quantitatively MAdCAM-1 expression in relation to early and advanced liver diseases (ii) Define the fine structure of vascular plexuses/lymphatics in the portal tract on which MAdCAM-1 is expressed. METHODS: Using alkaline phosphatase anti-alkaline phosphatase methodology on paraffin embedded tissue sections (n=28) from cirrhotic individuals who underwent orthotopic liver transplant, we evaluated MAdCAM-1 expression and compared with pre-cirrhotic, fulminant hepatitis B, and non-cirrhotic portal hypertension tissue sections. The positive controls included normal colon tissue with negative controls without primary antibody and isotype-matched purified IgG. We developed a real time PCR to quantify levels of MAdCAM-1 mRNA in our samples. RESULTS: MAdCAM-1 was expressed in 27/28 of the cirrhotic sections, localized primarily to septal areas within (i) endothelium of the peribiliary vascular plexus (PBP) (ii) lymphoid aggregates, with absence from normal, non-cirrhotic portal hypertension and pre-cirrhotic livers. There was significant upregulation of MAdCAM-1 mRNA in cirrhosis (p<0.011), consistent with immunohistochemical analysis. CONCLUSIONS: MAdCAM-1 is up-regulated in cirrhosis with expression on PBP and lymphoid aggregates. MAdCAM-1 is likely to contribute to the localization and recruitment of α4ß7 lymphocytes during the pathogenesis of cirrhosis. MAdCAM-1 could be a useful marker of advanced liver disease. Further studies with respect to the expression of MAdCAM-1 in the presence of reversible and non-reversible stages of liver disease may be of merit.
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Inmunoglobulinas/metabolismo , Cirrosis Hepática/metabolismo , Hígado/metabolismo , Mucoproteínas/metabolismo , Adulto , Moléculas de Adhesión Celular , Colon/metabolismo , Endotelio Linfático/metabolismo , Femenino , Humanos , Inmunohistoquímica , Hígado/irrigación sanguínea , Tejido Linfoide/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismo , Adulto JovenRESUMEN
OBJECTIVES: Conspiracy theories are associated with significant COVID-19 health consequences including lower engagement with protective behaviours. This study uses sensemaking theory, a process of constructing meanings through interpersonal exchanges that enable people to interpret their world to explain the theoretical process underlying the development of conspiratorial beliefs around COVID-19 within Black African and Caribbean communities in the UK. DESIGN: Qualitative, in-depth interviews were used. METHODS: Twenty-eight members of the communities were recruited: semi-structured interviews were analysed using grounded theory. RESULTS: Our findings provide an explanation of how an environment of crisis combined with current and historical mistrust, perceived injustice and inequality provided a context in which alternative conspiracy narratives could thrive. The nature of these conspiratorial beliefs made more sense to many of our respondent's than institutional sources (such as the UK Government). Critically, these alternative beliefs helped respondents shape their decision-making, leading to non-engagement with COVID protective behaviours. CONCLUSIONS: We conclude that the uncertainty of the pandemic, combined with historical and contemporary perceived injustice and mistrust, and a lack of specific identity-aligned messaging, created a perfect environment for conspiratorial sense-making to thrive. This alternative sensemaking was inconsistent with the health-protection messaging espoused by the Government. To ensure all groups in society are protected, and for health promotion messages to take purchase, the experiences of different target audiences must be taken into account, with sensemaking anchored in lived experience.
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COVID-19 , Humanos , Etnicidad , Teoría Fundamentada , Promoción de la Salud , Reino UnidoRESUMEN
AIM: To retrospectively evaluate the characteristic clinicopathological spectrum in patients with suspicion of IgG4-related disease (IgG4RD). METHODS: Winpath histology database from January 2011 to April 2018 identified all suspected IgG4RD cases wherein IgG4 immunohistochemistry was performed. The histology slides were reviewed to categorise cases into Boston criteria groups-highly suggestive of IgG4RD, probable IgG4RD and insufficient evidence. Information regarding clinical data, treatment received, follow-up and serum IgG4 levels was obtained from medical records and AllScripts Patient Administration System (APAS) clinical database. RESULTS: The study included 204 patients and the most common sites of biopsy/resection were pancreas and duodenum. The most common clinical presentation was fibroinflammatory lesion or mass/lump. On histology, 54/204 (26.47%) cases showed typical storiform fibrosis, 65/204 (32.64%) had >10 IgG4+ plasma cells per high power field and only one case showed thrombophlebitis (0.49%). There were 14/204 (6.78%) cases categorised as highly suggestive of IgG4RD; 8 of these showed high serum IgG4 levels and were managed clinically as true IgG4RD. CONCLUSION: Histological diagnosis of IgG4RD remains challenging, as not all characteristic features are always present especially in small biopsies. Due to the novelty of its experience, fear of over diagnosis in the context of malignancy and features overlapping with diseases of similar clinical scenario, diagnosis of IgG4RD has become more puzzling. Further multicentre clinical trials/studies are advisable.
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Enfermedades Autoinmunes , Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/patología , Estudios Retrospectivos , Biopsia , Inmunoglobulina G , Reino Unido/epidemiología , Enfermedades Autoinmunes/diagnósticoRESUMEN
The European Association for the Study of the Liver (EASL) has recently (June 2022) produced new clinical practice guidelines for the investigation and management of haemochromatosis, to replace the previous document published in 2010. Here, we provide an overview of the principal changes recommended for the investigation and management of haemochromatosis arising from these guidelines and highlight particular areas where evidence is lacking and where future focus on specific research would improve patient treatment and outcomes. The guideline provides several important new recommendations that will have a meaningful impact on patient management. Specifically, the use of hepatic elastography as a non-invasive assessment of fibrosis, erythrocytapheresis as an alternative treatment modality to classical phlebotomy, surveillance for hepatocellular carcinoma, dietary recommendations in patients with haemochromatosis and guidance on controversial topics including the management of P.C282Y/p.H63D compound heterozygotes, which have been a source of controversy within the field. It is anticipated that the new guidance will affect the management of haemochromatosis patients commonly seen in gastroenterology, liver and related clinics (e.g. haematology and rheumatology) and with this publication we intend to highlight these changes so as to empower clinicians with the confidence to bring these improvements to their translational practice in the treatment of these patients.