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1.
Sci Rep ; 13(1): 12507, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532752

RESUMO

Gout is a common metabolic disorder characterized by deposits of monosodium urate monohydrate crystals (tophi) in soft tissue, triggering intense and acute arthritis with intolerable pain as well as articular and periarticular inflammation. Tophi can also promote chronic inflammatory and erosive arthritis. 2015 ACR/EULAR Gout Classification criteria include clinical, laboratory, and imaging findings, where cases of gout are indicated by a threshold score of ≥ 8. Some imaging-related findings, such as a double contour sign in ultrasound, urate in dual-energy computed tomography, or radiographic gout-related erosion, generate a score of up to 4. Clearly, the diagnosis of gout is largely assisted by imaging findings; however, dual-energy computed tomography is expensive and exposes the patient to high levels of radiation. Although musculoskeletal ultrasound is non-invasive and inexpensive, the reliability of the results depends on expert experience. In the current study, we applied transfer learning to train a convolutional neural network for the identification of tophi in ultrasound images. The accuracy of predictions varied with the convolutional neural network model, as follows: InceptionV3 (0.871 ± 0.020), ResNet101 (0.913 ± 0.015), and VGG19 (0.918 ± 0.020). The sensitivity was as follows: InceptionV3 (0.507 ± 0.060), ResNet101 (0.680 ± 0.056), and VGG19 (0.747 ± 0.056). The precision was as follows: InceptionV3 (0.767 ± 0.091), ResNet101 (0.863 ± 0.098), and VGG19 (0.825 ± 0.062). Our results demonstrate that it is possible to retrain deep convolutional neural networks to identify the patterns of tophi in ultrasound images with a high degree of accuracy.


Assuntos
Artrite Gotosa , Gota , Humanos , Reprodutibilidade dos Testes , Gota/diagnóstico por imagem , Ácido Úrico/metabolismo , Ultrassonografia/métodos , Tomografia Computadorizada por Raios X/métodos , Inflamação , Aprendizado de Máquina
2.
Acta Cardiol Sin ; 39(2): 213-241, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36911549

RESUMO

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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36520129

RESUMO

Phenotype modification therapy has emerged as one of the main treatment objectives of periodontal plastic surgery. However, long-term data on the stability of gingival thickness gains are not available. This study examined the kinetics of mucosal thickness gain as a measure of phenotype modification therapy following treatment of multiple gingival recession defects with vestibular incision subperiosteal tunnel access (VISTA). Six patients with 14 recession type (RT) II teeth were treated using VISTA and subepithelial connective tissue grafts (SCTG). Scanned images of study casts at pre- and postoperative periods (6 to 66 months) were digitally superimposed for quantitative evaluation of soft tissue dimensional changes. Mucosal thickness gains ranged from 1.0 ± 0.7 mm (1 mm apical to cement-enamel junction [CEJ]) to 1.4 ± 0.4 mm (5 mm apical to CEJ). The gingival thickness gains remained relatively stable, with thickness gains at 66 months of 0.5 ± 0.8, 0.9 ± 0.6, 1.1 ± 0.6, 1.0 ± 0.4, and 1.2 ± 0.6 mm at 1, 2, 3, 4 and 5 mm apical to the CEJ, respectively. Treatment of multiple gingival recession defects with VISTA and SCTG led to stable gingival thickness gains and shows promise as a strategy for phenotype modification therapy.


Assuntos
Retração Gengival , Humanos , Retração Gengival/diagnóstico por imagem , Retração Gengival/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Raiz Dentária/cirurgia , Retalhos Cirúrgicos , Gengiva/cirurgia , Tecido Conjuntivo/transplante
5.
Front Immunol ; 13: 992819, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275719

RESUMO

Background: Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection. Methods: This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan's National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders. Results: The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81-1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71-1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02-1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves' disease (aHR: 6.06, 95% CI: 1.27-28.8) and Hashimoto's thyroiditis (aHR 1.49, 95% CI 1.01-2.21) among IBT users. Conclusions: IBT use increases the risk of autoimmune thyroid diseases (Hashimoto's thyroiditis and Graves' disease) in patients with HCV infection to a greater extent than non-IBT use.


Assuntos
Doença de Graves , Doença de Hashimoto , Hepatite C Crônica , Hepatite C , Humanos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Ribavirina , Interferon-alfa , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , Hepatite C/complicações , Doença de Hashimoto/complicações
6.
Clin Biochem ; 108: 27-41, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35843269

RESUMO

BACKGROUND: Sjogren's syndrome (SS) is a systemic autoimmune disease featured with a dry mouth and dry eyes. Several autoantibodies, including anti-SSA, anti-SSB, antinuclear antibodies can be detected in patients with SS. Oxidation-specific epitopes (OSEs) can be formed from malondialdehyde (MDA)-modified protein adducts and trigger chronic inflammation. In this study, our purposes were used serum levels of anti-MDA-modified peptide adducts autoantibodies to evaluate predictive performance by machine learning algorithms in primary Sjögren's syndrome (pSS) and assess the association between pSS and healthy controls. METHODS: Three novel MDA-modified peptide adducts, including immunoglobulin (Ig) gamma heavy chain 1 (IGHG1)102-131, complement factor H (CFAH)1045-1062, and Ig heavy constant alpha 1 (IGHA1)307-327 were identified and validated. Serum levels of protein, MDA-modified protein adducts, MDA, and autoantibodies recognizing unmodified peptides and MDA-modified peptide adducts were measured. Statistically significance in correlations and odds ratios (ORs) were estimated. RESULTS: The random forest classifier utilized autoantibodies combination composed of IgM anti-IGHG1102-131, IgM anti-IGHG1102-131 MDA and IgM anti-IGHA1307-327 achieved predictive performance as an accuracy of 88.0%, a sensitivity of 93.7%, and a specificity of 84.4% which may be as potential diagnostic biomarkers to differentiate patients with pSS from rheumatoid arthritis (RA), and secondary SS in RA and HCs. CONCLUSIONS: Our findings imply that low levels of IgA anti-IGHG1102-131 MDA (OR = 2.646), IgA anti-IGHG1102-131 (OR = 2.408), IgA anti-CFAH1045-1062 (OR = 2.571), and IgA anti-IGHA1307-327 (OR = 2.905) may denote developing risks of pSS, respectively.


Assuntos
Artrite Reumatoide , Síndrome de Sjogren , Anticorpos Antinucleares , Autoanticorpos , Biomarcadores , Fator H do Complemento , Epitopos , Feminino , Humanos , Imunoglobulina A , Imunoglobulina M , Malondialdeído , Peptídeos , Síndrome de Sjogren/diagnóstico
7.
J Clin Oncol ; 40(21): 2391-2392, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35549388
8.
J Dent ; 120: 104083, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35247470

RESUMO

OBJECTIVES: Studies have evaluated changes in hard tissue following immediate implant placement (IIP) through cone beam computed tomography (CBCT) imaging. This study compared the 3D volumetric changes of the alveolar bone at immediate implant sites with 2D linear measurement outcomes by using a novel image analysis workflow. METHODS: Preoperative and 6-month postoperative CBCT images of patients who underwent IIP and bone grafting in the maxillary esthetic area were acquired. Linear and volumetric measurements of buccal bone dimensions were taken using a specially designed workflow. The 2D and 3D measurements were compared, and their correlations were determined. RESULTS: Images from 13 patients (13 implants) were analyzed. Linear measurements revealed that the general linear buccal bone loss was less than 1mm in all segments. The 3D volumetric bone reduction (reported as median [first quantile, third quantile]) in the vertical, cervical, middle, and apical segments was 14.27 [11.33, 30.66] mm3 (51.30 [42.78, 66.91]%), 16.20 [10.35, 30.52] mm3 (18.20 [9.88, 24.74]%), 17.48 [8.42, 21.17] mm3 (24.05 [12.39, 28.22]%), and 6.87 [3.88, 9.45] mm3 (11.34 [5.14, 22.54]%), respectively. Significant positive correlations between 2D and 3D measurements were consistently identified in the cervical and middle segments, but no significant correlation was noted in the vertical segment. CONCLUSIONS: The results revealed that linear measurements could not fully represent volumetric bone dimensional changes. Performing volumetric measurements and 3D rendering could be valuable in presenting the actual amount and topography of peri-implant bone remodeling. CLINICAL SIGNIFICANCE: Linear measurements only partially represent the real-life event of 3D bone changes at immediate implant sites. Factors affecting hard tissue alterations following IIP should be reassessed using 3D volumetric measurement outcomes.


Assuntos
Estética Dentária , Alvéolo Dental , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Maxila/diagnóstico por imagem , Maxila/cirurgia , Projetos Piloto , Alvéolo Dental/cirurgia
9.
Int J Mol Sci ; 23(5)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35269745

RESUMO

Calcium pyrophosphate (CPP) deposition disease (CPPD) is a form of CPP crystal-induced arthritis. A high concentration of extracellular pyrophosphate (ePPi) in synovial fluid is positively correlated with the formation of CPP crystals, and ePPi can be upregulated by ankylosis human (ANKH) and ectonucleotide pyrophosphatase 1 (ENPP1) and downregulated by tissue non-specific alkaline phosphatase (TNAP). However, there is currently no drug that eliminates CPP crystals. We explored the effects of the histone deacetylase (HDAC) inhibitors (HDACis) trichostatin A (TSA) and vorinostat (SAHA) on CPP formation. Transforming growth factor (TGF)-ß1-treated human primary cultured articular chondrocytes (HC-a cells) were used to increase ePPi and CPP formation, which were determined by pyrophosphate assay and CPP crystal staining assay, respectively. Artificial substrates thymidine 5'-monophosphate p-nitrophenyl ester (p-NpTMP) and p-nitrophenyl phosphate (p-NPP) were used to estimate ENPP1 and TNAP activities, respectively. The HDACis TSA and SAHA significantly reduced mRNA and protein expressions of ANKH and ENPP1 but increased TNAP expression in a dose-dependent manner in HC-a cells. Further results demonstrated that TSA and SAHA decreased ENPP1 activity, increased TNAP activity, and limited levels of ePPi and CPP. As expected, both TSA and SAHA significantly increased the acetylation of histones 3 and 4 but failed to block Smad-2 phosphorylation induced by TGF-ß1. These results suggest that HDACis prevented the formation of CPP by regulating ANKH, ENPP1, and TNAP expressions and can possibly be developed as a potential drug to treat or prevent CPPD.


Assuntos
Pirofosfato de Cálcio , Condrocalcinose , Pirofosfato de Cálcio/metabolismo , Condrocalcinose/tratamento farmacológico , Condrocalcinose/genética , Condrocalcinose/metabolismo , Condrócitos/metabolismo , Inibidores de Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Humanos , Pirofosfatases/genética , Pirofosfatases/metabolismo
10.
Arthritis Res Ther ; 24(1): 52, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35189943

RESUMO

BACKGROUND: Corticosteroid injection for knee osteoarthritis is limited by its modest duration of treatment effect. The liposome formulation of dexamethasone sodium phosphate (TLC599) was developed for the sustained relief of osteoarthritis pain. This clinical study was conducted to evaluate the efficacy and safety of TLC599 at two dose levels in patients with knee osteoarthritis. METHODS: A randomized, double-blinded, placebo-controlled study was conducted in 75 patients with osteoarthritis of the knee from 13 study centers. Patients were randomized and administered a single intra-articular injection of TLC599 or placebo and assessed for efficacy and safety for 24 weeks. Patient-reported outcomes included the Western Ontario and McMaster Universities Arthritis (WOMAC) Index for pain and function and visual analog scale for pain. RESULTS: TLC599 at 12 mg demonstrated significantly greater reduction in WOMAC pain through 12 weeks (least squares (LS) mean difference = - 0.37, p = 0.0027) and through 24 weeks (LS mean difference = - 0.35, p = 0.0037) when compared to placebo. TLC599 12 mg also exhibited significantly greater improvement in function when compared to placebo at 24 weeks (LS mean difference = - 0.26, p = 0.0457). TLC599 18 mg did not significantly improve pain or function in comparison with placebo. The use of acetaminophen during the study was less in both TLC599 groups in comparison with placebo. No major or unexpected safety issues were reported. CONCLUSIONS: In participants with symptomatic knee osteoarthritis, TLC599 is a well-tolerated treatment that reduces pain and improves function for up to 24 weeks, a longer duration than that reported for existing IA treatments. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03005873 . Registered on 29 December 2016.


Assuntos
Osteoartrite do Joelho , Método Duplo-Cego , Humanos , Ácido Hialurônico , Injeções Intra-Articulares , Articulação do Joelho , Resultado do Tratamento
11.
J Clin Oncol ; 40(11): 1206-1219, 2022 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-35044851

RESUMO

PURPOSE: H1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection. MATERIALS AND METHODS: Patients with HBV, HCV, or dual HBV-HCV infection were enrolled from Taiwan's National Health Insurance Research Database and examined for the period from January 1, 2006, to December 31, 2015. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the association between AH use and HCC risk. RESULTS: We included patients with HBV infection (n = 521,071), HCV (n = 169,159), and dual HBV-HCV (n = 39,016). Patients with HBV, HCV, or dual virus infection who used AHs exhibited significantly lower risk of HCC relative to patients who did not use AH, with their adjusted hazard ratio being 0.489 (95% CI, 0.455 to 0.524), 0.484 (95% CI, 0.450 to 0.522), and 0.469 (95% CI, 0.416 to 0.529), respectively. Furthermore, there was a dose-response relationship between AH use and the risk of HCC in the HBV cohort. The adjusted hazard ratios were 0.597 (95% CI, 0.530 to 0.674), 0.528 (0.465 to 0.600), 0.470 (0.416 to 0.531), and 0.407 (0.362 to 0.457) for AH use of 28-42, 43-63, 64-119, and ≥ 120 cumulative defined daily doses, respectively, relative to no AH use. Additionally, there was also a dose-response relationship between AH use and the risk of HCC in the HCV and dual HBV-HCV cohorts. CONCLUSION: AH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed.


Assuntos
Carcinoma Hepatocelular , Hepatite B , Hepatite C , Neoplasias Hepáticas , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/prevenção & controle , Hepacivirus , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Vírus da Hepatite B , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Antagonistas dos Receptores Histamínicos , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle
12.
Rheumatology (Oxford) ; 61(5): 1849-1856, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-34534283

RESUMO

OBJECTIVES: RA damages the joints and increases the risks of total knee replacement (TKR) and total hip replacement (THR). However, the benefits of biologics in preventing TKR or THR remain unclear. METHODS: This retrospective nationwide study used the 2000-2013 claims-based National Health Insurance dataset. Biologics are reimbursed for refractory cases. The risks of TKR and THR in the biologic cohort were compared with those of an age- and sex-matched csDMARD cohort. A multivariate Cox regression model was used to investigate the benefits of bDMARDs for TKR and THR. RESULTS: TKR was performed in 5979 biologic cases and 11 958 matched controls, of which 249 (4.16%) and 871 (7.28%) cases received TKR, respectively. THR was performed in 6245 biologic cases and 12 490 matched controls, of which 159 (2.55%) and 516 (4.13%) cases had THR, respectively. The biologic cohort had significantly lower incidence rates of TKR (11.73 vs 16.33/1000 person-years, P < 0.001) and THR (7.09 vs 9.16/1000 person-years, P < 0.001). After adjustment for confounding factors, the regular bDMARD subgroup (average dose >0.95 defined daily dose/day) had significantly lower risks of TKR (aHR: 0.55, 95% CI: 0.38, 0.81) and THR (aHR: 0.63, 95% CI: 0.40, 0.98). Those without MTX use, with steroid use, with biologic switch, and overlapping antiphospholipid syndrome had significantly higher risks of TKR and THR. CONCLUSIONS: Compared with the csDMARD cohort, the risks of TKR and THR in the bDMARD cohort were the same as those in the low-to-moderate dose subgroups and significantly lower in those with regular bDMARD use.


Assuntos
Artrite Reumatoide , Artroplastia de Quadril , Artroplastia do Joelho , Produtos Biológicos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/cirurgia , Produtos Biológicos/uso terapêutico , Humanos , Estudos Retrospectivos
13.
Biomed J ; 44(5): 627-635, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34740571

RESUMO

BACKGROUND: Transcrestal sinus floor elevation is a reliable procedure when additional bone height is needed for maxillary implant placement. However, the grafted bone undergoes remodeling and the dimensional stability of grafted bone height may be affected by several clinical factors, including graft material, sinus anatomy and the morphology of grafted space. METHODS: This retrospective study examined patients who had undergone transcrestal sinus floor elevation with synthetic biphasic calcium phosphate and single implant placement. The reduction of sinus graft height (GHR) after 6-8 months healing period was measured with cone-beam computed tomography (CBCT) images. Correlating factors, including vertical amount of implant protrusion (IP), sinus width, and the morphology of grafted space were analyzed by Spearman's correlation test. RESULTS: A total of 25 implant sites were analyzed. The mean GHR was 0.57 ± 0.49 mm, which was positively correlated with IP, vertical elevation height (VEH), and the ratio of vertical to horizontal elevation of the grafted space. However, GHR was not correlated with sinus width and mesial-distal or buccal-palatal width of the grafted space. CONCLUSIONS: Synthetic biphasic calcium phosphate used in transcrestal sinus floor elevation underwent shrinkages and graft remodeling. Grafted height reduction was associated with IP, VEH, and the ratio of vertical to horizontal elevation of the grafted space.


Assuntos
Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Remodelação Óssea , Tomografia Computadorizada de Feixe Cônico , Humanos , Maxila/diagnóstico por imagem , Maxila/cirurgia , Seio Maxilar , Estudos Retrospectivos
14.
Front Immunol ; 12: 736036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659225

RESUMO

Background: Previous study revealed proton pump inhibitors (PPIs) have an effect on gut microbiota. Alteration of the microbiome causes changes of the host immune system and then induces the development of autoimmune diseases (ADs). This study aimed to explore the possible association between PPIs use and ADs. Methods: This study was conducted using data from the Taiwan National Health Insurance Research Database in the period between 2002 and 2015. We performed multivariate and stratified analysis through the Kaplan-Meier method and Cox proportional hazard models to estimate the association between proton pump inhibitor use and the risk of autoimmune diseases. Results: Of the 297,099 patients treated with PPI identified, the overall mean (SD) age was 49.17 (15.63) years and 56.28% of the subjects was male. As compared with the non-PPI group, the adjusted hazard ratio (aHR) were higher for incident organ specific ADs such as Graves disease (aHR=3.28), Hashmoto thyroiditis (aHR=3.61), autoimmune hemolytic anemia (aHR=8.88), immune thrombocytopenic purpura (aHR=5.05) Henoch-Schonlein pupura (aHR=4.83) and Myasthenia gravis (aHR=8.73). Furthermore, the adjusted hazard ratio (aHR) were also higher for incident systemic ADs such as ankylosing spondylitis (aHR=3.67), rheumatoid arthritis (aHR=3.96), primary Sjogren syndrome (aHR=7.81), systemic lupus erythemtoasus (aHR=7.03). systemic vasculitis (aHR=5.10), psoriasis (aHR=2.57), systemic scleroderma (aHR=15.85) and inflammatory myopathy (aHR=37.40). Furthermore, we observed no dose-dependent effect between PPI use and the risk of ADs. Conclusions: Our retrospective population-based cohort study showed that the prescription of proton pump inhibitors is associated with a higher risk of ADs.


Assuntos
Doenças Autoimunes/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia , Fatores de Tempo , Adulto Jovem
15.
Biology (Basel) ; 10(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34356509

RESUMO

Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) is rapidly produced under proinflammatory stimuli, thereby feeding back to downregulate excessive inflammation. In this study, we used the stable, inducible expressions of wild-type (WT) MCPIP1 and an MCPIP1-D141N mutant in T-REx-293 cells by means of a tetracycline on (Tet-on) system. We found that WT MCPIP1 but not MCPIP1-D141N mutant expression dramatically increased apoptosis, caspase-3, -7, -8, and -9 activation, and c-Jun N-terminal kinase (JNK) phosphorylation in TNF-α-treated cells. The pan-caspase inhibitor, z-VAD-fmk, and the caspase-1 inhibitor, z-YVAD-fmk, but not the JNK inhibitor, SP600125, significantly reversed apoptosis and caspase activation in TNF-α/MCPIP1-treated cells. Surprisingly, MCPIP1 itself was also cleaved, and the cleavage was suppressed by treatment with the pan-caspase inhibitor and caspase-1 inhibitor. Moreover, MCPIP1 was found to contain a caspase-1/-4 consensus recognition sequence located in residues 234~238. As expected, the WT MCPIP1 but not the MCPIP1-D141N mutant suppressed NF-κB activation, as evidenced by inhibition of IκB kinase (IKK) phosphorylation and IκB degradation using Western blotting, IKK activity using in vitro kinase activity, and NF-κB translocation to nuclei using an immunofluorescence assay. Interestingly, MCPIP1 also significantly inhibited importin α3 and importin α4 expressions, which are major nuclear transporter receptors for NF-κB. Inhibition of NF-κB activation further downregulated expression of the caspase-8 inhibitor, cFLIP. In summary, the results suggest that MCPIP1 could enhance the TNF-α-induced apoptotic pathway through decreasing NF-κB activation and cFLIP expression.

16.
Clin Rheumatol ; 40(9): 3755-3763, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33646447

RESUMO

OBJECTIVE: To compare Pneumocystis jirovecii pneumonia (PJP) risk between patients with autoimmune rheumatic diseases (ARD) and the general population METHODS: We identified patients with ARD recorded in the National Health Insurance Research Database of Taiwan from 2002 to 2015 and randomly selected a comparison cohort from the general population matched for age and sex. We analyzed PJP risk stratified by sex, age, comorbidities, and medications using Cox proportional hazard model. RESULTS: We enrolled 103,117 patients with ARD. PJP risk significantly increased in patients with any ARD and with each individual ARD like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SjS), polymyositis and dermatomyositis (PM/DM), systemic sclerosis (SSc), and systemic vasculitis. Patients with PM/DM showed prominent risk with incidence rate of 12.47/100,000 patient year (95% confidence interval (CI), 32.16-86.70). In a time-dependent Cox proportional hazard model with comorbidities and medications as covariates, PM/DM, SSc, SLE, and SjS significantly increased adjusted hazard ratios (aHR) of 5.40, 5.12, 4.09, and 3.64, respectively (95% CI of 2.82-10.35, 2.16-12.13, 2.41-6.95, and 2.06-6.42, respectively). AHR after adjusting for male sex, cancer, human immunodeficiency virus infection (HIV), and interstitial lung disease also significantly increased. Use of daily oral steroid dose of >10 mg conferred the highest risk followed by mycophenolate. Use of injected steroids, cyclophosphamide, biological agents, methotrexate, and cyclosporine conferred a significantly higher risk. CONCLUSION: Underlying ARD significantly predisposes patients to PJP, with PM/DM posing the highest threat. In addition to underlying disease, comorbidities and concomitant immunosuppressants are major risks. The strongest risk is recent daily steroid dose of >10 mg. Mycophenolate seems to be a more prominent risk factor than cyclophosphamide. Key Points • Autoimmune rheumatic diseases (ARD) significantly increased the overall risk of PJP, and so did each individual ARD. • Use of steroids, mycophenolate, cyclophosphamide, biological agents, methotrexate, and cyclosporine all significantly increased risk of PJP. • Male, elderly, malignancy, HIV, and interstitial lung disease are also related to increased risk of PJP. • Underlying ARD, comorbidities, and use of immunosuppressant should all be considered in determining the overall risk of PJP.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Pneumocystis carinii , Pneumonia por Pneumocystis , Doenças Reumáticas , Idoso , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Masculino , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/epidemiologia , Doenças Reumáticas/complicações , Doenças Reumáticas/epidemiologia
17.
Sci Rep ; 11(1): 1612, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452297

RESUMO

The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a population-based propensity-score-matched cohort study using Taiwan's National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose-response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either < 224 or ≥ 224 (hazard ratio [HR]: 2.407, 95% confidence interval [CI] 1.412-7.790; HR: 2.143, 95% CI 1.046-4.393, respectively) increased risk of developing osteonecrosis of the jaw. In conclusion, the risk of BRONJ is significantly higher in patients with pSS compared with the general population.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Síndrome de Sjogren/patologia , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Bases de Dados Factuais , Difosfonatos/administração & dosagem , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Taiwan/epidemiologia
18.
J Formos Med Assoc ; 120(1 Pt 2): 318-326, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33148453

RESUMO

BACKGROUND/PURPOSE: To evaluate the therapeutic responsiveness of office-based salivary gland ductal irrigation in patients with chronic sialoadenitis. METHODS: Between August 2017 and April 2019, 55 patients comprising the following three disease groups were enrolled: Sjogren's syndrome: 39 patients; postradiotherapy sialoadenitis: ten patients; and post-RAI sialoadenitis: six patients. Quantitative salivary scintigraphy was recorded, and a formulated questionnaire including the Summated Xerostomia Inventory was utilized to assess acute/chronic symptoms. All patients received at least three serial salivary gland ductal irrigations with a one-month interval in our outpatient department. RESULTS: The general response rates for each disease groups are as follows: Sjogren's syndrome: 61.5% (24/39); postradiotherapy: 60% (6/10); and post-RAI: 83.3% (5/6). Among the patients with Sjogren's syndrome, the parotid scintigraphic Tmin showed a significant positive correlation with the responsiveness of salivary irrigation (P = 0.046), whereas the treatment tended to be irresponsive in patients who previously took medicine for their related discomfort (P = 0.009). In the postradiotherapy and post-RAI groups, no significant factors were found to be associated with the responsiveness of irrigation. CONCLUSION: Simple salivary ductal irrigation without complex equipment can be performed as an outpatient procedure to alleviate glandular swelling or xerostomia in patients with Sjogren's syndrome, postradiotherapy sialoadenitis or post-RAI sialoadenitis, and it can be considered an alternative management approach for patients refractory to conventional strategies.


Assuntos
Sialadenite , Síndrome de Sjogren , Doença Crônica , Humanos , Cintilografia , Ductos Salivares , Sialadenite/etiologia , Sialadenite/terapia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/terapia
19.
Clin Rheumatol ; 40(2): 537-546, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32671658

RESUMO

The data concerning the association between dengue viruses (DV) infection and autoimmune diseases (ADs) remain unclear and are scarce. This nationwide population-based cohort study assessed the risk of ADs among patients with DV infection. We analyzed Taiwanese medical data from the Registry of the National Notifiable Disease Reporting System of Taiwan's Centers for Disease Control between 1998 and 2015 and identified patients with DV infection. From the entire general population data in the National Health Insurance Research Database, we randomly selected a comparison cohort that was individual matching by age, sex, residence, and index date. We analyzed the risk of ADs using a Cox proportional hazards regression model stratified by sex, age, and residence. We enrolled 29,365 patients with DV infection (50.68% men; mean age, 44.13 years) and 117,460 age-, sex-, and residence-matched controls in the present study. The incidence rates of organ-specific ADs were nonsignificantly higher in the DV cohort than in the non-DV control cohort. An approximately 70% lower risk of primary Sjogren syndrome (pSS) was evident in the DV cohort than in the non-DV control cohort with an adjusted hazard ratio of 0.30 (95% confidence interval 0.13-0.67) after adjusting for comorbidities in matched design. By contrast, the other systemic ADs were nonsignificantly lower in the DV cohort than in the non-DV control cohort. This nationwide long-term cohort study demonstrated that patients with DV infection had a lower risk of primary Sjogren syndrome than those without DV infection. Key Points • This retrospective, longitudinal cohort observational study shows that patients with DV infection had a lower risk of pSS than those without DV infection. • The DV cohort had an approximately 70% lower risk of pSS than the control group, with a multivariate-adjusted HR of 0.30. • On the basis of this result, we contended that DV infection has a protective effect that reduces the risk of pSS.


Assuntos
Dengue , Síndrome de Sjogren , Viroses , Adulto , Estudos de Coortes , Dengue/complicações , Dengue/epidemiologia , Feminino , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia , Taiwan/epidemiologia
20.
Medicine (Baltimore) ; 99(46): e23180, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181695

RESUMO

This study compared implant outcomes following maxillary sinus floor augmentation (MSFA) in edentulous patients with a residual alveolar bone height ≤3 mm. Four techniques were evaluated: 1-stage bone-added osteotome sinus floor elevation procedure (BAOSFE) with simultaneous implant placement; 2-stage BAOSFE with delayed implant placement; 1-stage lateral window sinus floor elevation with simultaneous implant placement; and 2-stage lateral window sinus floor elevation with delayed implant placement. Patients were followed for 18 to 72 months (mean: 52.5 months) after prosthesis placement. Data were analyzed with cone-beam computed tomography. A total of 96 implants from 71 patients were analyzed; pretreatment, there were no significant differences between patients. Total implant survival was 98.9%. The mean residual bone height was significantly higher in the 1-stage BAOSFE group than the other groups (P < .01); 1 implant in this group failed at 3 months. There was no significant difference in total bone height gain between groups. However, the bone height gain of 1st sinus lifting with 2-stage BAOSFE was significantly lower than the 2-stage lateral window procedure (P < .01). There was no prosthesis failure. The favorable implant outcomes suggest these 1-stage and 2-stage MSFA procedures should be considered as alternative treatment options for patients with extremely atrophic posterior maxilla.


Assuntos
Osso e Ossos/cirurgia , Seios Paranasais/cirurgia , Próteses e Implantes/tendências , Levantamento do Assoalho do Seio Maxilar/estatística & dados numéricos , Pesos e Medidas , Osso e Ossos/anormalidades , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Nasais/instrumentação , Procedimentos Cirúrgicos Nasais/métodos , Osteotomia/métodos , Radiografia/métodos , Radiografia/estatística & dados numéricos , Levantamento do Assoalho do Seio Maxilar/instrumentação , Levantamento do Assoalho do Seio Maxilar/métodos , Estatísticas não Paramétricas , Resultado do Tratamento
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