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OBJECTIVE: To evaluate the risk of end-stage kidney disease (ESKD) in lupus nephritis (LN) patients using tubulointerstitial lesion scores. METHODS: Clinical profiles and histopathological presentations of 151 biopsy-proven LN patients were retrospectively examined. Risk factors of ESKD based on characteristics and scoring of their tubulointerstitial lesions (e.g. interstitial inflammation [II], tubular atrophy [TA], and interstitial fibrosis [IF]) were analyzed. RESULTS: The mean age of 151 LN patients was 36 years old, and 136 (90.1%) were female. The LN cases examined included: class I/II (n = 3, 2%), class III/IV (n = 119, 78.8%), class V (n = 23, 15.2%), and class VI (n = 6, 4.0%). The mean serum creatinine level was 1.4 mg/dl. Tubulointerstitial lesions were recorded in 120 (79.5%) patients. Prior to receiving renal biopsy, 9 (6.0%) patients developed ESKD. During the follow-up period (mean, 58 months), an additional 47 patients (31.1%) progressed to ESKD. Multivariate analyses identified serum creatinine (hazard ratio [HR]: 1.7, 95% confidence interval [CI]: 1.42-2.03, p < 0.001) and IF (HR: 3.2, 95% CI: 1.58-6.49, p = 0.001) as independent risk factors of ESKD. Kaplan-Meier analysis further confirmed a heightened risk of ESKD associated with IF. CONCLUSION: Tubulointerstitial involvement is commonly observed in histopathological presentation of LN. However, IF, rather than II, or TA, was found to increase the risk of ESKD in our cohort. Therefore, to predict renal outcome in LN patients prior to adjusting immunosuppressive treatment, degree of IF should be reviewed.
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OBJECTIVES: To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation. METHODS: Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies. RESULTS: During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy. CONCLUSIONS: HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment.
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Antirreumáticos , Productos Biológicos , Antígeno HLA-B27 , Neoplasias , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Antígeno HLA-B27/inmunología , Femenino , Masculino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Factores de Riesgo , Inflamación/inmunología , Inflamación/tratamiento farmacológicoRESUMEN
Background and Objective: The International Map of Axial Spondyloarthritis (IMAS) explores the physical, psychological, and social experiences of patients with axial spondyloarthritis (axSpA). This initiative is now being expanded to Taiwan as the Taiwanese Map of Axial Spondyloarthritis (TMAS). We aim to provide rheumatologists with insights into the perspectives of Taiwanese patients, enabling physicians to better understand the unmet needs of these patients and optimize their management. Materials and Methods: The TMAS is a cross-sectional study gathering data through an online survey of axSpA patients, promoted by the Ankylosing Spondylitis Caring Society of R.O.C. (ASCARES), conducted from July 2017 to March 2018 by Ipsos, and analyzed by the Health & Territory Research (HTR) group of the University of Seville. The questionnaire includes 99 questions that cover domains such as patient profile, diagnosis, habits/lifestyle, employment status, physical/psychological health status, social support, use of healthcare services, and treatments. Results: A total of 112 axSpA patients were included in this survey. The mean age was 38.6 years and 75.0% were male. The average diagnostic delay was 3 years, and 19.6% reported extra-articular manifestations. Out of the 49 respondents who reported HLA-B27 information, 35 were HLA-B27-positive. The disease burden was high, with a mean BASDAI score of 4.9 and 75.9% having a mild to moderate degree of spinal stiffness. Furthermore, they were socially and psychologically burdened, with 88.4% experiencing work-related issues and 25.9% suffering from anxiety. Conclusions: The TMAS sheds light on the overall perspective of axSpA patients in Taiwan. The TMAS shows shorter diagnostic delay compared to patients from the EMAS. However, high disease activity and significant psychological distress still trouble the patients, causing functional impairments and even leading to career failures. Understanding the perspective of axSpA patients can help rheumatologists adjust treatment strategies to their unmet needs and improve their disease outcomes.
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Espondiloartritis , Espondilitis Anquilosante , Humanos , Masculino , Adulto , Femenino , Espondiloartritis/diagnóstico , Espondiloartritis/psicología , Antígeno HLA-B27 , Estudios Transversales , Diagnóstico TardíoRESUMEN
Background: Pulmonary arterial hypertension (PAH), defined as the presence of a mean pulmonary artery pressure > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) > 2 Wood units based on expert consensus, is characterized by a progressive and sustained increase in PVR, which may lead to right heart failure and death. PAH is a well-known complication of connective tissue diseases (CTDs), such as systemic sclerosis, systemic lupus erythematosus, Sjogren's syndrome, and other autoimmune conditions. In the past few years, tremendous progress in the understanding of PAH pathogenesis has been made, with various novel diagnostic and screening methods for the early detection of PAH proposed worldwide. Objectives: This study aimed to obtain a comprehensive understanding and provide recommendations for the management of CTD-PAH in Taiwan, focusing on its clinical importance, prognosis, risk stratification, diagnostic and screening algorithm, and pharmacological treatment. Methods: The members of the Taiwan Society of Cardiology (TSOC) and Taiwan College of Rheumatology (TCR) reviewed the related literature thoroughly and integrated clinical trial evidence and real-world clinical experience for the development of this consensus. Conclusions: Early detection by regularly screening at-risk patients with incorporations of relevant autoantibodies and biomarkers may lead to better outcomes of CTD-PAH. This consensus proposed specific screening flowcharts for different types of CTDs, the risk assessment tools applicable to the clinical scenario in Taiwan, and a recommendation of medications in the management of CTD-PAH.
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IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato-hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.
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Enfermedades Autoinmunes/inmunología , Linfocitos B/inmunología , Fibrosis/inmunología , Enfermedad Relacionada con Inmunoglobulina G4/inmunología , Inmunoglobulina G/inmunología , Inflamación/inmunología , Linfocitos T/inmunología , Animales , Linfocitos B/patología , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Inmunoglobulina E/inmunología , Inmunoglobulina G/química , Enfermedad Relacionada con Inmunoglobulina G4/genética , Enfermedad Relacionada con Inmunoglobulina G4/patología , Inflamación/patología , Proteínas NLR/inmunología , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Receptores Toll-Like/inmunologíaRESUMEN
Recent studies have reported that peroxisome proliferator-activated receptor α (PPARα) agonist decreases intrahepatic resistance, whereas PPARγ agonist reduces portosystemic shunts (PSSs) and splanchnic angiogenesis in cirrhotic rats. The present study investigated the effects of a 21-day treatment with the dual PPARα/γ agonist aleglitazar (Ale) on progressive abnormalities in bile-duct-ligated and thioacetamide-induced cirrhotic rats with portal hypertension (PH). In vivo and in vitro effects were evaluated. Chronic Ale treatment significantly up-regulated PPARα/PPARγ receptors and down-regulated tumor necrosis factor-α (TNF-α) and NF-κB expression in the liver, splanchnic tissues, collateral vessels, and intestines of cirrhotic rats with PH. Notably, Ale improved PH by the suppression of systemic/tissue inflammation, hepatic fibrosis, hepatic Rho-kinase-mediated endothelin-1 hyperresponsiveness, intrahepatic/mesenteric angiogenesis, vascular endothelial growth factor expression, PSS, intestinal mucosal injury, and hyperpermeability in cirrhotic rats. Acute Ale treatment inhibited TNF-α-enhanced endothelin-1-induced contraction of primary hepatic stellate cells, vascular endothelial growth factor-induced migration/angiogenesis of liver sinusoidal endothelial cells, and TNF-α-induced disruption of Caco-2 cell monolayer-epithelial barrier. The present study suggested that Ale can potentially treat relevant abnormalities through the inhibition of inflammatory, vasoconstrictive, angiogenic, and mucosal-disrupted pathogenic markers in cirrhosis. Overall, chronic Ale treatment ameliorated PH syndrome by the suppression of hepatic fibrogenesis, neoangiogenesis, vasoconstrictor hyperresponsiveness, splanchnic vasodilatation, and PSS; and decreased intestinal mucosal injury and hyperpermeability in cirrhotic rats.
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Hipertensión Portal/tratamiento farmacológico , Circulación Hepática/efectos de los fármacos , Cirrosis Hepática/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Oxazoles/farmacología , PPAR alfa/agonistas , PPAR gamma/agonistas , Circulación Esplácnica/efectos de los fármacos , Tiofenos/farmacología , Animales , Células CACO-2 , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Background: Reversal of alcohol-induced peroxisome proliferator-activated receptor (PPAR) α (PPARα) and PPARδ dysfunction has been reported to decrease the severity of alcoholic steatohepatitis (ASH). Autophagy is essential for cell survival and tissue energy homeostasis. Emerging evidence indicates that alcohol-induced adipose tissue (AT) autophagy dysfunction contributes to injury in the intestine, liver, and AT of ASH. Methods: The effects and mechanisms of dual PPARα/δ agonist elafibranor on autophagy stimulation were investigated using mice with ASH. Results: C57BL/6 mice on ethanol diet showed AT dysfunction, disrupted intestinal barrier, and ASH, which was accompanied by alcohol-mediated decrease in PPARα, PPARδ, and autophagy levels in intestine, liver, and AT. Chronic treatment with elafibranor attenuated AT apoptosis and inflammation by restoration of tissue PPARα, PPARδ, and autophagy levels. In ASH mice, alcohol-induced AT dysfunction along with increased fatty acid (FA) uptake and decreased free FA (FFA) release from AT was inhibited by elafibranor. The improvement of AT autophagy dysfunction by elafibranor alleviated inflammation and apoptosis-mediated intestinal epithelial disruption in ASH mice. Acute elafibranor incubation inhibited ethanol-induced ASH-mice-sera-enhanced autophagy dysfunction, apoptosis, barrier disruption, and intracellular steatosis in Caco-2 cells and primary hepatocytes (PHs). Conclusion: Altogether, these findings demonstrated that the PPARα/δ agonist, elafibranor, decreased the severity of liver injury by restoration of alcohol-suppressed AT autophagy function and by decreasing the release of apoptotic markers, inflammatory cytokines, and FFA, thereby reducing intestinal epithelium disruption and liver inflammation/apoptosis/steatosis in ASH mice. These data suggest that dual PPAR agonists can serve as potential therapeutic agents for the management of ASH.
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Chalconas/administración & dosificación , Hígado Graso Alcohólico/tratamiento farmacológico , Intestinos/efectos de los fármacos , Hígado/efectos de los fármacos , Propionatos/administración & dosificación , Tejido Adiposo/citología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Autofagia/efectos de los fármacos , Hígado Graso Alcohólico/genética , Hígado Graso Alcohólico/metabolismo , Humanos , Intestinos/citología , Intestinos/lesiones , Hígado/lesiones , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR delta/genética , PPAR delta/metabolismoRESUMEN
In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory [TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite] profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic [(SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1)] markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.
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Cafeína/farmacología , Hígado Graso/prevención & control , Enfermedades del Sistema Inmune/prevención & control , Obesidad/inmunología , Obesidad/metabolismo , Adiposidad/efectos de los fármacos , Animales , Células Cultivadas , Dieta Alta en Grasa , Hígado Graso/metabolismo , Enfermedades del Sistema Inmune/etiología , Enfermedades del Sistema Inmune/patología , Inflamación/prevención & control , Resistencia a la Insulina , Lipogénesis/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Obesidad/etiología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
AIMS: Increases in the systemic vasodilator adrenomedullin and the renal vasoconstrictors thromboxane A2 in cirrhotic patients are pathogenic factors for the development of functional acute kidney injury (AKI), including pre-renal azotemia (PRA) and hepatorenal syndrome (HRS), which is associated with high mortality. This study aims to find biomarkers that can diagnose HRS at an early stage, to enable treatment as soon as possible. METHODS: Acute decompensated cirrhotic patients who had been admitted to hospital were enrolled in this prospective cohort study. Blood and urinary samples were collected immediately after admission. In addition to initially categorizing AKI cases into PRA, acute tubular necrosis (ATN), and HRS groups, their final diagnosis was adjudicated by a nephrologist and a hepatologist who checked the corrected and misclassification rates for significant biomarkers. RESULTS: The cut-off values for serum adrenomedullin and urinary thromboxane B2 (TXB2 ), when used as predictors for functional AKI (adrenomedullin >283 pg/mL, urinary TXB2 >978 [pg/mg urinary creatinine]), for HRS (adrenomedullin >428, urinary TXB2 >1604), and for good terlipressin plus albumin treatment responders (adrenomedullin >490, urinary TXB2 >1863), were observed. Patients with HRS who could be treated, due to high mortality, had significantly higher serum adrenomedullin and urinary TXB2 levels compared to HRS patients receiving standard treatment. In addition to predicting 60-day mortality, a combination of these two markers further increased diagnostic accuracy for HRS among functional AKI. CONCLUSIONS: Prompt diagnosis of HRS by differentiating it from PRA and ATN can be achieved by using serum adrenomedullin and urinary TXB2 in acute decompensated cirrhotic patients. In combination with severe clinical courses, these two markers are useful to select HRS patients who cannot be treated.
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Enfermedades Autoinmunes , Enfermedad Relacionada con Inmunoglobulina G4 , Fibrosis Retroperitoneal , Enfermedades Autoinmunes/diagnóstico , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/tratamiento farmacológico , Riñón , Fibrosis Retroperitoneal/complicaciones , Fibrosis Retroperitoneal/diagnósticoRESUMEN
Background: Anti-MDA5 antibody-bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) and/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD, especially with regard to the mortality rate, are unknown. Methods: We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Results: In total, 39 (55%) patients presented with DM/PM, but 32 (45%) did not. In total, 22 of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA-5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among the 32 patients who did not have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio (OR) = 1.816, p = 0.032), presence of anti-Ro-52 antibody (OR = 1.676, p = 0.018), elevated C-reactive protein (CRP, OR = 4.354, p < 0.001) and carcinoembryonic antigen (CEA, OR = 2.625, p = 0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p = 0.009), CRP (p = 0.001) and CEA (p = 0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR = 0.245, p = 0.017) and multivariate (OR = 0.058, p = 0.036) regressions, indicating that they may be a protective factor in relation to RPILD (OR = 0.543, p = 0.008) or fatality (OR = 0.707, p = 0.012), which was also demonstrated in subgroup analyses. Conclusions: In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might conversely be a protective factor in anti-MDA5+ patients.
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BACKGROUND: Immune-mediated diseases (IMDs) after nucleic acid-based vaccines have been sporadically reported since their introduction during the worldwide COVID-19 crisis. Confirming their cause-effect association remains challenging. We analysed the effects of AZD1222 (ChAdOx1 nCoV-19), BNT-162b2, and/or mRNA-1273 on the development &/or deterioration of IMDs in terms of the time of clinical onsets of IMDs after exposure to these vaccines. METHODS: We retrospectively reviewed 78 in-patients in Taipei Veterans General Hospital, who presented with IMDs within 120 days after receiving AZD1222, BNT-162b2, &/or mRNA-1273 vaccinations in Taiwan from May 2021 to April 2022. The duration from inoculation to development of IMD was analysed by two-tailed Kolmogorov-Smirnov (K-S) test for goodness of fit. RESULTS: The average time to new IMDs or flare-up of the diseases following vaccinations was 36 ± 26 days for all 91 events in these 78 patients. The onset time of IMDs after vaccinations was not haphazard as analysed by two-tailed K-S test for overall 91 events (40 new and 51 deteriorating episodes, p < 0.001). The IMDs presenting as non-connective tissue diseases (non-CTDs) have a shorter duration of incubation after vaccinations than those of CTDs (<14.7 days, 95 % confidence interval [CI], 3.0 to 26.4, p = 0.014). Furthermore, systemic vasculitis and type 2 inflammatory diseases were observed exclusively in those receiving AZD1222. CONCLUSION: AZD1222, BNT-162b2, or mRNA-1273 influence the activities of IMDs in ways yet to be explored. High index of suspicion to IMDs after nucleic acid-based vaccine inoculation against COVID-19 may be important for primary care physicians.
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COVID-19 , Enfermedades del Sistema Inmune , Humanos , ChAdOx1 nCoV-19 , Vacuna BNT162 , Vacuna nCoV-2019 mRNA-1273 , Estudios Retrospectivos , Vacunación/efectos adversos , COVID-19/prevención & control , Vacunación Basada en Ácidos NucleicosRESUMEN
BACKGROUND: Graft failure resulting from rejection or any other adverse event usually originates from an aberrant and/or exaggerated immune response and is often catastrophic in renal transplantation. So, it is essential to monitor patients' immune status for detecting a rejection/graft failure early on. METHODS: We monitored the sequence change of complementary determining region 3 (CDR3) in B-cell receptor (BCR) immunoglobulin heavy-chain (IGH) immune repertoire (iR) in 14 renal transplant patients using next-generation sequencing (NGS), correlating its diversity to various clinical events occurring after transplantation. BCR-IGH-CDR3 in peripheral blood mononuclear cells was sequenced along the post-transplantation course by NGS using the iRweb server. RESULTS: Datasets covering VDJ regions of BCR-IGH-CDR3 indicated clonal diversity (D50) variations along the post-transplant course. Furthermore, principal component analysis showed the clustering of these sequence variations. A total of 544 shared sequences were identified before transplantation. D50 remained low in three patients receiving rituximab. Among them, one's D50 resumed after 3 m, indicating graft tolerance. The D50 rapidly increased after grafting and decreased thereafter in four patients without rejection, decreased in two patients with T-cell-mediated rejection (TCMR) and exhibited a sharp down-sliding after 3 m in two patients receiving donations after cardiac death (DCD). In another two patients with TCMR, D50 was low just before individual episodes, but either became persistently low or returned to a plateau, depending on the failure or success of the immunosuppressive treatments. Shared CDR3 clonal expansions correlated to D50 changes. Agglomerative hierarchical clustering showed a commonly shared CDR3 sequence and at least two different clusters in five patients. CONCLUSIONS: Clonal diversity in BCR-IGH-CDR3 varied depending on clinical courses of 14 renal transplant patients, including B-cell suppression therapy, TCMR, DCD, and graft tolerance. Adverse events on renal graft failure might lead to different clustering of BCR iR. However, these preliminary data need further verification in further studies for the possible applications of iR changes as genetic expression biomarkers or laboratory parameters to detect renal graft failure/rejection earlier.
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OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized heterogeneous, subacute, and usually silent autoimmune disease involving many organs with protean manifestations. However, high IgG4 in serum is not necessarily indicating an IgG4-RD. The aims of this study were to investigate the clinical relevance of high serum IgG4 level in IgG4-RD or non IgG4-RD patients, and to see if IgG4-RD in Taiwan differs from that in other parts of the world. METHODS: Eight hundred forty-five patients with high IgG4 were retrospectively reviewed from January 2002 to May 2020 in Taipei Veteran General Hospital. Two hundred sixty-seven patients fulfilled IgG4-RD criteria and were categorized into pancreato-hepato-biliary disease, retroperitoneal fibrosis and/or aortitis, head/neck-limited disease, classic Mikulicz syndrome with systemic involvement, CNS-limited disease, sclerosing vasculitis, skin-limited disease, and sensorineural hearing disease. These manifestations were correlated to smoking, atopy, hyper-IgE/eosinophilia, aging, malignancies, and hypocomplementemia. Five hundred seventy-eight patients were not fulfilling the criteria but were also analyzed for the prevalence of allergy, malignancy, connective tissue diseases, lung diseases, and infections. RESULTS: In IgG4-RD patients, 124 (46.4%) smoked. Top 4 clinical subtypes included Mikulicz syndrome with systemic involvement (33.3%), pancreato-hepatobiliary disease (31.4%), head/neck disease (19.4%), and retroperitoneal fibrosis/aortitis (12.7%). Top 4 co-morbid conditions included high serum IgE/eosinophilia (46.2%), hypocomplementemia (34%), malignancies (13.4%), and allergy (13.4%). Pancreato-biliary disease was associated with high IgE/eosinophilia (r2 = 0.380, P = 0.025) and malignancy (r2 = 0.211, P = 0.027), Miculicz syndrome with allergy (r2 = 0.396, P < 0.01) and high IgE/eosinophil (r2 = 0.396, P < 0.01), CNS diseases (r2 = 0.973, P = 0.035) and sclerosing vasculitis (r2 = 1, P < 0.01) with advanced age respectively, with the latter being also related to atopy and high IgE/eosinophilia (r2 = 1, p < 0.01). CONCLUSION: Smoking may precipitate IgG4-RD. IgG4-RD with pancreato-hepatobiliary disease is closely related to allergy and neoplasm, and those with Mikulicz syndrome may result from atopy. Elderly IgG4-RD patients tend to develop CNS pathology parallel to advancing of age. The disease may probably be originated from an unknown mechanism that may sporadically evolve into malignancies.
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Enfermedades Autoinmunes , Enfermedad Relacionada con Inmunoglobulina G4 , Fibrosis Retroperitoneal , Anciano , Enfermedades Autoinmunes/epidemiología , Humanos , Inmunoglobulina G , Enfermedad Relacionada con Inmunoglobulina G4/epidemiología , Fibrosis Retroperitoneal/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: This study aimed to evaluate whether the role-play (RP) of real patients by medical students as part of interactive clinical reasoning training can improve medical students' clinical performance. METHODS: A total of 26 medical students volunteered to portray real patients within this program and were treated as the RP group while the other 72 students as the non-RP group. In the interactive morning meeting, the medical students practiced how to approach the RP student as if they were encountering a real patient. All students were evaluated by mini-clinical evaluation exercises (mini-CEX) before and after this training program. RESULTS: We found that all students had an increased total mini-CEX score after 4-week training, especially for interviewing skills. Notably, after training, the RP students had significantly elevated total mini-CEX scores (51.23 ± 1.06 vs 53.12 ± 1.11, p = 0.028), and for counselling (7.15 ± 0.14 vs 7.54 ± 0.18, p = 0.015) and overall clinical competence (7.27 ± 0.15 vs 7.65 ± 0.16, p = 0.030). In contrast, the non-RP students had lower scores compared with the RP group, as revealed by both the pre- and post-training tests. Moreover, their mini-CEX scores were not improved after training. CONCLUSION: Medical students who were motivated to RP real patients had better performance scores than those who did not. In addition, RP can enhance their counselling skills and clinical competences.
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Competencia Clínica/normas , Simulación de Paciente , Desempeño de Papel , Estudiantes de Medicina , Femenino , Humanos , Masculino , Evaluación de Programas y Proyectos de Salud , Mejoramiento de la CalidadRESUMEN
BACKGROUND: Sarcopenia is an ever-increasingly recognized entity in aging or chronically-ill individuals. A recent surge of researches came out on sarcopenia in rheumatoid arthritis (RA). However, the results varied widely. We tried to assess the prevalence of and associated factors with sarcopenia in patients with RA. METHODS: We searched the investigations dealing with the prevalence of and associated factors with sarcopenia in RA from PubMed, EMBASE, CENTRAL, EBSCOhost, Airiti Library, CEPS, CNKI and J-STAGE from the inception to January 11, 2020. Effects regarding prevalence and associated factors were extracted and evaluated by random-effects model. Sensitivity analysis was also performed. RESULTS: Seventeen studies containing 3,140 RA subjects were identified. After exclusion of outliers, the pooled prevalence of sarcopenia was 31%. Neither ongoing-study districts nor diagnostic modalities affected prevalence significantly. Any associated factors being mentioned in at least two publications were analyzed, yielding functional limitation (Steinbrocker stage III/IV), high CRP and RF seropositivity as the significant risk factors. Based on disease durations, we carried out meta-regression and found DAS28 and HAQ are predictive models. There was no alteration in the interpretation of results from sensitivity analysis after removal of any studies skewed in sampling distribution. CONCLUSIONS: The prevalence of sarcopenia in patients with RA is high, compared to that in general counterparts. Disease duration rather than age, residing area or diagnostic modalities influences sarcopenia development; DAS28 and HAQ predict occurrence. High index of suspicion to facilitate early detection of sarcopenia in RA patients is important.
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Artritis Reumatoide , Sarcopenia , Artritis Reumatoide/complicaciones , Artritis Reumatoide/epidemiología , Humanos , Prevalencia , Análisis de Regresión , Factores de Riesgo , Sarcopenia/epidemiología , Sarcopenia/etiologíaRESUMEN
Bacterial translocation (BT) and splenomegaly contribute to cirrhosis-associated immune dysfunction (CAID) including T cell depletion, infection, and chronic inflammation. ß-blockers have been reported to decrease BT and improve splenomegaly. This study explores the modulation of ß1 and ß2 adrenergic receptors (ADRB1/ADRB2) by propranolol treatment on the peripheral and splenic immune dysfunction of cirrhotic mice. In vivo experiments were performed in bile duct ligation (BDL)- and thioacetamide (TAA)-cirrhotic mice receiving two weeks of propranolol treatment. Acute effects of propranolol were evaluated in T-helper (Th) cells isolated from spleen of cirrhotic mice. Over-expression of ß1 and ß2 adrenergic receptors (ADRB1/ADRB2) in spleen and T lymphocytes was associated with high peripheral/splenic lipopolysaccharide binding protein levels. Moreover, a decrease in Th cells percentage, increase in Treg subset, and cytokines were accompanied by increased apoptosis, proliferation, and reduced white pulp hyperplasia in cirrhotic mice, which were counteracted by propranolol treatment. The Th-cell depletion, systemic inflammation, BT, and infection were improved by chronic propranolol treatment. Acute propranolol treatment inhibited apoptosis, Treg-conditioned differentiation, and promoted Th2-conditioned differentiation through ADRB-cyclic adenosine monophosphate (cAMP) signals in cirrhotic mice. In conclusion, suppression of ADRB1 and ADRB2 expressions in spleen and splenic T lymphocytes by acute and chronic propranolol treatment ameliorate systemic and splenic immune dysfunction in cirrhosis.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Propranolol/uso terapéutico , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Antagonistas Adrenérgicos beta/farmacología , Animales , Modelos Animales de Enfermedad , Humanos , Cirrosis Hepática/inmunología , Masculino , Ratones , Propranolol/farmacología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
Alcoholic cirrhosis (AC) leads to enormous disease burden and occupies a substantial proportion in the etiology of hepatocellular carcinoma (HCC), but scarce attention has been paid to this topic. Besides, propranolol has been reported to decrease the rate of HCC in viral hepatitis. We conducted a retrospective tertiary-center cohort study to identify the HCC incidence in AC patients with or without propranolol. A total of 1,046 AC patients with hospitalization had been screened, and those with regular follow-up for three years or otherwise until the date of malignancy diagnosis without meeting exclusion criteria were enrolled; finally, 23 AC patients with propranolol and 46 AC patients without propranolol were analyzed after twofold propensity-score matching. The cumulative incidence of HCC was lower in the propranolol group (log-rank test, P = 0.046). Furthermore, we undertook the meta-analysis of annual incidence of HCC in AC patients, and 1,949 publications were screened, within which eight studies were analyzed; the pooled annual incidence was 2.41%, which was higher than the calculated annual incidence of HCC in our AC cohort with propranolol (1.45%). In conclusion, propranolol is associated with decreased risk of HCC incidence in patients with AC.
RESUMEN
BACKGROUND: In non-alcoholic steatohepatitis (NASH), muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice. METHODS: In vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat-methionine and choline deficient diet-induced NASH mice and palmitate-pretreated C2C12 myoblast cells. RESULTS: Resveratrol treatment improved grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. The SIRT1-dependent effect of muscle wasting was associated with the suppression of oxidative stress, upregulation of antioxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, upregulation of lipolytic genes and the reduction of fatty infiltration in limb muscles of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The beneficial effects of resveratrol were abolished by EX527. CONCLUSIONS: Our study suggests that chronic resveratrol treatment is a potential strategy for amelioration of hepatic steatosis and muscle wasting in NASH mouse model.