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1.
J Med Virol ; 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864567

RESUMO

This study assessed T-cell responses in individuals with and without a positive antibody response to SARS-CoV-2, in symptomatic and asymptomatic individuals during the COVID-19 pandemic. Participants were drawn from the TwinsUK cohort, grouped by (a) presence or absence of COVID-associated symptoms (S+, S-), logged prospectively through the COVID Symptom Study app, and (b) anti-IgG Spike and anti-IgG Nucleocapsid antibodies measured by ELISA (Ab+, Ab-), during the first wave of the UK pandemic. T-cell helper and regulatory responses after stimulation with SARS-CoV-2 peptides were assessed. Thirty-two participants were included in the final analysis. Fourteen of 15 with IgG Spike antibodies had a T-cell response to SARS-CoV-2-specific peptides; none of 17 participants without IgG Spike antibodies had a T-cell response (χ2 : 28.2, p < 0.001). Quantitative T-cell responses correlated strongly with fold-change in IgG Spike antibody titer (ρ = 0.79, p < 0.0001) but not to symptom score (ρ = 0.17, p = 0.35). Humoral and cellular immune responses to SARS-CoV-2 are highly correlated. We found no evidence of cellular immunity suggestive of SARS-CoV2 infection in individuals with a COVID-19-like illness but negative antibodies.

3.
RMD Open ; 8(2)2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35868737

RESUMO

OBJECTIVE: The lifetime recurrence rate (RR) of axial spondyloarthritis (axSpA) among first-degree relatives (FDR) and the effect of proband's gender, HLA-B27 and radiographic status is unclear. Our 35-year-follow-up family study has enabled these issues to be addressed. METHODS: In 1985, 363 ankylosing spondylitis (AS) probands (members of the Swiss AS Patient Society) and 806 FDR recruited into the study, completed questionnaires regarding axSpA manifestations, underwent a physical examination and most also underwent pelvic radiography and HLA-B27 typing. At follow-up in 2018-2019, of the former participants whose current addresses could be retrieved, 162 had died and 485 (125 patients with AS plus 360 FDR) completed a postal questionnaire. RESULTS: At follow-up, 48 of 177 HLA-B27(+) FDR had developed axSpA, an RR of 27.1% (95% CI 20.6% to 33.7%). 27/148 (18.2%) children of AS probands (modified New York (mNY) criteria) were affected versus 2/50 (4.0%) children of non-radiographic axSpA probands (p=0.0138, OR=5.36; 95% CI 1.23 to 23.40). Children of female probands were more often affected (12/22; 54.5%) than of male probands (15/78; 19.2%) (p=0.0003; OR=4.89; 95% CI 1.96 to 12.23). This increased risk applies equally to sons and daughters. CONCLUSION: The lifetime RR of axSpA for HLA-B27(+) FDR is substantial (27.1%), and disease severity (as defined by radiographic sacroiliitis by the mNY criteria) is an additional risk factor. Affected mothers pass on the disease significantly more often to their offspring than do affected fathers. These findings may lead to better assessment of lifetime risk for axSpA in the offspring. Moreover, investigation of this gender effect may uncover additional putative disease susceptibility factors.


Assuntos
Espondiloartrite Axial , Espondilartrite , Espondilite Anquilosante , Criança , Feminino , Seguimentos , Antígeno HLA-B27/genética , Humanos , Masculino , Estudos Prospectivos , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Espondilartrite/genética , Espondilite Anquilosante/diagnóstico
4.
Anat Rec (Hoboken) ; 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35723491

RESUMO

New imaging and biomechanical approaches have heralded a renaissance in our understanding of crocodylian anatomy. Here, we review a series of approaches in the preparation, imaging, and functional analysis of the jaw muscles of crocodylians. Iodine-contrast microCT approaches are enabling new insights into the anatomy of muscles, nerves, and other soft tissues of embryonic as well as adult specimens of alligators. These imaging data and other muscle modeling methods offer increased accuracy of muscle sizes and attachments without destructive methods like dissection. 3D modeling approaches and imaging data together now enable us to see and reconstruct 3D muscle architecture which then allows us to estimate 3D muscle resultants, but also measurements of pennation in ways not seen before. These methods have already revealed new information on the ontogeny, diversity, and function of jaw muscles and the heads of alligators and other crocodylians. Such approaches will lead to enhanced and accurate analyses of form, function, and evolution of crocodylians, their fossil ancestors and vertebrates in general.

5.
Front Genet ; 13: 913196, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35754823

RESUMO

Systemic sclerosis (SSc) is an autoinflammatory, fibrotic condition of unknown aetiology. The presence of detectable autoantibodies against diverse nuclear antigens, as well as strong HLA associations with disease, suggest autoimmune involvement, however the links between endogenous and exogenous risk factors and SSc pathology remain undetermined. We have conducted a genetic analysis of HLA inheritance in two independent and meta-analysed cohorts of 1,465 SSc cases and 13,273 controls, including stratified association analyses in clinical and autoantibody positive subgroups of disease. Additionally, we have used patient genotypes to impute gene dosages across the KIR locus, encoding paired activating and inhibitory lymphocyte receptors for Class I HLA ligands, to conduct the largest analysis of KIR-HLA epistatic interactions in SSc to date. We confirm previous Class II HLA associations with SSc risk and report a new Class I association with haplotype HLA-B*44:03-HLA-C*16:01 at genome-wide significance (GWS). We further report statistically significant HLA associations with clinical and serological subtypes of disease through direct case-case comparison, and report a new association of HLA-DRB1*15:01, previously shown to bind topoisomerase-1 derived peptides, with anti-topoisomerase (ATA) positive disease. Finally, we identify genetic epistasis between KIRs and HLA class I ligands, suggesting genetic modulation of lymphocyte activation may further contribute to an individual's underlying disease risk. Taken together, these findings support future functional investigation into endogenous immunological and environmental stimuli for disrupted immune tolerance in SSc.

6.
RMD Open ; 8(1)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35523521

RESUMO

OBJECTIVE: Axial spondyloarthritis (axSpA) comprises both radiographic and non-radiographic disease. However, the paucity of specific objective measures for the disease and current classification criteria showing suboptimal specificity contribute to disease heterogeneity observed in clinical practice and research. We used a historical cohort of patients with axSpA to assess sources of heterogeneity. METHODS: The study involved 363 axSpA probands recruited from membership of the Swiss Ankylosing Spondylitis Patient Society. Participants underwent examination by a rheumatologist, completed questionnaires and provided blood samples for HLA typing. Patients underwent radiography of sacroiliac joints and were categorised according to the New York (NY) criteria (ankylosing spondylitis (AS) or non-radiographic axSpA (nr-axSpA)) and HLA-B27 status. Genetic characterisation by single nucleotide polymorphism microarray was performed and AS polygenic risk scores (PRS) were calculated. RESULTS: Considerable heterogeneity was observed. The male to female ratio for AS (NY+) was 3:1, but 1:1 for nr-axSpA. For HLA-27(+) AS, the ratio was 2.5:1, but nearly 1:1 for HLA-B27(-) disease. Women with nr-axSpA had strikingly lower mean PRS and lower HLA-B27 prevalence than men with nr-axSpA or NY(+) male and female patients with AS. PRS was able to distinguish male but not female patients with nr-axSpA from related healthy first-degree relatives. Radiographic sacroiliitis was strongly associated with HLA-B27, especially in men. CONCLUSION: Women clinically diagnosed with axSpA but without radiographic sacroiliitis as a group have a disease that is distinct from AS by the modified New York criteria overall and from nr-axSpA in men. Given the high degree of heterogeneity, stratified or adjusted analysis of effectiveness studies is indicated, taking genetics, sex and radiographic damage (sacroiliitis) into account.


Assuntos
Espondiloartrite Axial , Sacroileíte , Espondilartrite , Espondilite Anquilosante , Feminino , Antígeno HLA-B27/genética , Humanos , Masculino , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Espondilartrite/genética , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/epidemiologia , Espondilite Anquilosante/genética
7.
Arthritis Rheumatol ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507331

RESUMO

OBJECTIVES: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. METHODS: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. RESULTS: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP = 0.63), which was similar to the heritability of PsC (h2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. CONCLUSION: Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

8.
Children (Basel) ; 9(4)2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35455612

RESUMO

Multiple studies have shown the microbiota to be abnormal in patients with spondyloarthritis (SpA). The purpose of this study was to explore the genetic contributions of these microbiota abnormalities. We analyzed the impact of HLA-B27 on the microbiota of children at risk for SpA and compared the microbiota of HLA-B27+ pediatric offspring of ankylosing spondylitis (AS) patients with that of HLA-B27+ children with SpA. Human DNA was obtained from the offspring for determination of HLA-B27 status and polygenic risk score (PRS). Fecal specimens were collected from both groups for sequencing of the V4 region of the 16S ribosomal RNA gene. Among the offspring of AS patients, there was slight clustering by HLA-B27 status. After adjusting for multiple comparisons, five operational taxonomic units (OTUs) representing three unique taxa distinguished the HLA-B27+ from negative children: Blautia and Coprococcus were lower in the HLA-B27+ offspring, while Faecalibacterium prausnitzii was higher. HLA-B27+ offspring without arthritis were compared to children with treatment-naïve HLA-B27+ SpA. After adjustments, clustering by diagnosis was present. A total of 21 OTUs were significantly associated with diagnosis state, including Bacteroides (higher in SpA patients) and F. prausnitzii (higher in controls). Thus, our data confirmed associations with B. fragilis and F. prausnitzii with juvenile SpA, and also suggest that the mechanism by which HLA-B27 is associated with SpA may not involve alterations of the microbiota.

9.
Genes Immun ; 23(2): 57-65, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379982

RESUMO

Uveitis is the most common form of intraocular inflammatory disease and is a significant cause of visual impairment worldwide. Aetiologically, uveitis can also be classified into infectious uveitis and non-infectious uveitis. The common non-infectious forms of uveitis include acute anterior uveitis (AAU), Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, birdshot chorioretinopathy (BSCR), sarcoid uveitis. In addition, a few monogenic autoinflammatory disorders can also cause uveitis, such as Blau Syndrome and haploinsufficiency of A20 (HA20). Although the exact pathogenesis of non-infectious uveitis is still unclear, it is well-recognised that it involves both genetic and environmental risk factors. A hallmark of uveitis is its strong associations with human leucocyte antigens (HLA). For examples, AAU, BD and BSCR are strongly associated with HLA-B27, HLA-B51, and HLA-A29, respectively. In uveitis studies, multiple GWAS have successfully been conducted and led to identification of novel susceptibility loci, for example, IL23R has been identified in BD, VKH and AAU. In this review, we summarize the latest progress on the genetic associations of both HLA and non-HLA genes with major forms of uveitis, including AAU, BD, VKH, BSCR, sarcoid uveitis, Blau Syndrome and HA20, and potential future research directions.


Assuntos
Artrite , Síndrome de Behçet , Sarcoidose , Sinovite , Uveíte Anterior , Uveíte , Síndrome de Behçet/genética , Antígenos HLA/genética , Antígeno HLA-B27 , Humanos , Sarcoidose/genética , Uveíte/genética , Uveíte Anterior/genética
10.
Ann Rheum Dis ; 81(6): 831-837, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35277388

RESUMO

OBJECTIVE: Factors predicting axial spondyloarthritis (axSpA) among first-degree relatives (FDRs) of ankylosing spondylitis (AS) patients need to be defined. We investigated the predictive value of the probands' HLA-B27 and radiographic sacroiliitis status on disease occurrence among their FDR. We also assessed the predictive value of features of the clinical history, including chronic inflammatory back pain (CIBP) and acute anterior uveitis (AAU), among the FDR and how they can be used to improve classification and diagnosis of axSpA. METHODS: In 1985, we studied 363 AS probands and 806 FDR who underwent rheumatologic examination, completed questionnaires, provided blood samples for HLA-typing and underwent radiography of sacroiliac joints. At follow-up in 2018-2019, 125 patients and 360 FDR were available for study, and completed a postal questionnaire about axSpA features. FDRs were asked to report whether after 1985 they had been diagnosed by Swiss rheumatologists as having axSpA. RESULTS: Among HLA-B27(+) FDR, axSpA occurred in 25.4%-26.3%, independent of the radiographic sacroiliitis status of the proband. AAU occurred in 13/34 (38.2%) FDR with axSpA vs 29/251 (11.6%) FDR without axSpA (p=0.00004, OR=4.74 95% CI 2.15 to 10.47). The presence of CIBP at baseline did not predict later occurrence of axSpA but combining CIBP and pain/discomfort at the thoracic spine and at anterior (ventral) chest wall ever, assessed at follow-up in 2018-2019, provided 83.1% sensitivity and 87.2% specificity for current axSpA. CONCLUSION: Occurrence of AAU among FDR of axSpA probands should prompt screening for axSpA. Moreover, co-occurrence of CIBP and pain/discomfort in the thoracic spine and at anterior chest wall as a three-question tool may further enhance clinical suspicion of axSpA among these FDR.


Assuntos
Espondiloartrite Axial , Sacroileíte , Espondilartrite , Espondilite Anquilosante , Uveíte Anterior , Dor nas Costas/genética , Antígeno HLA-B27/genética , Humanos , Sacroileíte/diagnóstico por imagem , Sacroileíte/epidemiologia , Sacroileíte/genética , Espondilartrite/diagnóstico , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/epidemiologia
11.
ACR Open Rheumatol ; 4(6): 528-533, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35352506

RESUMO

OBJECTIVE: We undertook this study to examine the X chromosome complement in participants with systemic sclerosis (SSc) as well as idiopathic inflammatory myopathies. METHODS: The participants met classification criteria for the diseases. All participants underwent single-nucleotide polymorphism typing. We examined X and Y single-nucleotide polymorphism heterogeneity to determine the number of X chromosomes. For statistical comparisons, we used χ2 analyses with calculation of 95% confidence intervals. RESULTS: Three of seventy men with SSc had 47,XXY (P = 0.0001 compared with control men). Among the 435 women with SSc, none had 47,XXX. Among 709 men with polymyositis or dermatomyositis (PM/DM), seven had 47,XXY (P = 0.0016), whereas among the 1783 women with PM/DM, two had 47,XXX. Of 147 men with inclusion body myositis (IBM), six had 47,XXY, and 1 of the 114 women with IBM had 47,XXX. For each of these myositis disease groups, the excess 47,XXY and/or 47,XXX was significantly higher compared with in controls as well as the known birth rate of Klinefelter syndrome or 47,XXX. CONCLUSION: Klinefelter syndrome (47,XXY) is associated with SSc and idiopathic inflammatory myopathies, similar to other autoimmune diseases with type 1 interferon pathogenesis, namely, systemic lupus erythematosus and Sjögren syndrome.

13.
PLoS One ; 17(1): e0261723, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35025912

RESUMO

Skeletal muscle atrophy is a physiological response to disuse, aging, and disease. We compared changes in muscle mass and the transcriptome profile after short-term immobilization in a divergent model of high and low responders to endurance training to identify biological processes associated with the early atrophy response. Female rats selectively bred for high response to endurance training (HRT) and low response to endurance training (LRT; n = 6/group; generation 19) underwent 3 day hindlimb cast immobilization to compare atrophy of plantaris and soleus muscles with line-matched controls (n = 6/group). RNA sequencing was utilized to identify Gene Ontology Biological Processes with differential gene set enrichment. Aerobic training performed prior to the intervention showed HRT improved running distance (+60.6 ± 29.6%), while LRT were unchanged (-0.3 ± 13.3%). Soleus atrophy was greater in LRT vs. HRT (-9.0 ±8.8 vs. 6.2 ±8.2%; P<0.05) and there was a similar trend in plantaris (-16.4 ±5.6% vs. -8.5 ±7.4%; P = 0.064). A total of 140 and 118 biological processes were differentially enriched in plantaris and soleus muscles, respectively. Soleus muscle exhibited divergent LRT and HRT responses in processes including autophagy and immune response. In plantaris, processes associated with protein ubiquitination, as well as the atrogenes (Trim63 and Fbxo32), were more positively enriched in LRT. Overall, LRT demonstrate exacerbated atrophy compared to HRT, associated with differential gene enrichments of biological processes. This indicates that genetic factors that result in divergent adaptations to endurance exercise, may also regulate biological processes associated with short-term muscle unloading.


Assuntos
Treino Aeróbico/métodos , Elevação dos Membros Posteriores/métodos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Transcriptoma/fisiologia , Adaptação Fisiológica , Animais , Terapia por Exercício , Feminino , Biblioteca Genômica , Humanos , Masculino , Condicionamento Físico Animal , Ratos , Análise de Sequência de RNA
14.
J Rheumatol ; 49(3): 274-280, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34853088

RESUMO

OBJECTIVE: Individuals with ankylosing spondylitis (AS) have a greater cardiovascular (CV) risk than those in the general population. The effect of tumor necrosis factor inhibitors (TNFis) on CV risk, including on the development of hypertension (HTN), remains unclear, with some data suggesting higher risk. We assessed the association of TNFi use with incident HTN in a longitudinal AS cohort. METHODS: Adults with AS enrolled in a prospective cohort in 2002-2018 were examined every 4-6 months. TNFi use during the preceding 6 months was ascertained at each study visit. We defined HTN by patient-reported HTN, antihypertensive medication use, or, on 2 consecutive visits, systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. We evaluated the association between TNFi use and the development of HTN with marginal structural models, estimated by inverse probability-of-treatment weighting, to account for time-dependent confounders and informative censoring. Potential confounders included age, sex, race, site, nonsteroidal antiinflammatory drug use, and disease activity. RESULTS: We included 630 patients without baseline HTN and with at least 1 year of follow-up. Of these, 72% were male, mean age was 39 ± 13 years, and 43% used TNFi at baseline. On follow-up (median 5 yrs), 129 developed incident HTN and 163 started on TNFi during follow-up. TNFi use was not associated with incident HTN (adjusted HR 1.10, 95% CI 0.83-1.37). CONCLUSION: In our prospective AS cohort, TNFi use was not significantly associated with incident HTN.


Assuntos
Antirreumáticos , Hipertensão , Espondilite Anquilosante , Adulto , Antirreumáticos/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espondilite Anquilosante/complicações , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/epidemiologia , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
15.
Lancet Rheumatol ; 4(1): e42-e52, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34778846

RESUMO

BACKGROUND: COVID-19 vaccines have robust immunogenicity in the general population. However, data for individuals with immune-mediated inflammatory diseases who are taking immunosuppressants remains scarce. Our previously published cohort study showed that methotrexate, but not targeted biologics, impaired functional humoral immunity to a single dose of COVID-19 vaccine BNT162b2 (Pfizer-BioNTech), whereas cellular responses were similar. Here, we aimed to assess immune responses following the second dose. METHODS: In this longitudinal cohort study, we recruited individuals with psoriasis who were receiving methotrexate or targeted biological monotherapy (ie, tumour necrosis factor [TNF] inhibitors, interleukin [IL]-17 inhibitors, or IL-23 inhibitors) from a specialist psoriasis centre serving London and South-East England. The healthy control cohort were volunteers without psoriasis, not receiving immunosuppression. Immunogenicity was evaluated immediately before, on day 28 after the first BNT162b2 vaccination and on day 14 after the second dose (administered according to an extended interval regimen). Here, we report immune responses following the second dose. The primary outcomes were humoral immunity to the SARS-CoV-2 spike glycoprotein, defined as titres of total spike-specific IgG and of neutralising antibody to wild-type, alpha (B.1.1.7), and delta (B.1.617.2) SARS-CoV-2 variants, and cellular immunity defined as spike-specific T-cell responses (including numbers of cells producing interferon-γ, IL-2, IL-21). FINDINGS: Between Jan 14 and April 4, 2021, 121 individuals were recruited, and data were available for 82 participants after the second vaccination. The study population included patients with psoriasis receiving methotrexate (n=14), TNF inhibitors (n=19), IL-17 inhibitors (n=14), IL-23 inhibitors (n=20), and 15 healthy controls, who had received both vaccine doses. The median age of the study population was 44 years (IQR 33-52), with 43 (52%) males and 71 (87%) participants of White ethnicity. All participants had detectable spike-specific antibodies following the second dose, and all groups (methotrexate, targeted biologics, and healthy controls) demonstrated similar neutralising antibody titres against wild-type, alpha, and delta variants. By contrast, a lower proportion of participants on methotrexate (eight [62%] of 13, 95% CI 32-86) and targeted biologics (37 [74%] of 50, 60-85; p=0·38) had detectable T-cell responses following the second vaccine dose, compared with controls (14 [100%] of 14, 77-100; p=0·022). There was no difference in the magnitude of T-cell responses between patients receiving methotrexate (median cytokine-secreting cells per 106 cells 160 [IQR 10-625]), targeted biologics (169 [25-503], p=0·56), and controls (185 [133-328], p=0·41). INTERPRETATION: Functional humoral immunity (ie, neutralising antibody responses) at 14 days following a second dose of BNT162b2 was not impaired by methotrexate or targeted biologics. A proportion of patients on immunosuppression did not have detectable T-cell responses following the second dose. The longevity of vaccine-elicited antibody responses is unknown in this population. FUNDING: NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London; The Psoriasis Association.

16.
Front Immunol ; 12: 777322, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880870

RESUMO

Major salivary gland ultrasonography (SGUS) is increasingly being recognized as having critical roles in differentiating primary Sjögren's syndrome (pSS) from other connective tissue disorders. Contrast-enhanced ultrasonography (CEUS) has been reported to evaluate microvascularity of lesions in different tissues with objective angiographic index, eliminating the observer-dependent defect of ultrasonography. However, there are few relevant studies concentrating on the application of CEUS in the diagnosis and assessment for pSS, and their clinical utility prospect remains uncertain. In this study, a total of 227 eligible patients were enrolled, including 161 pSS and 66 non-pSS patients with comprehensive ultrasonographic evaluation of the parotid and submandibular glands, including grayscale ultrasonography, color Doppler sonography (CDS), and CEUS. Compared with non-pSS, pSS patients had significantly higher grayscale ultrasound (US) scores and CDS blood grades in the parotid gland and significantly higher grayscale US and CEUS scores in the submandibular glands. Diagnostic model combining ultrasonographic signatures, anti-SSA/Ro60, and keratoconjunctivitis sicca (KCS) tests showed a remarkable discrimination [mean area under the curve (AUC)0.963 in submandibular glands and 0.934 in parotid glands] for pSS, and the nomogram provided excellent prediction accuracy and good calibration in individualized prediction of pSS. A combination of multiple ultrasonographical examinations of the major salivary glands (SGs) is a promising technique that may be used as a practical alternative to minor SG biopsy in the detection of pSS.


Assuntos
Síndrome de Sjogren/diagnóstico , Ultrassonografia/métodos , Adulto , Biomarcadores , Gerenciamento Clínico , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Imagem Multimodal/normas , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/patologia , Curva ROC , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Síndrome de Sjogren/etiologia , Glândula Submandibular/diagnóstico por imagem , Glândula Submandibular/patologia , Ultrassonografia/normas
17.
Int J Angiol ; 30(3): 228-242, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34776823

RESUMO

The question of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery remains among the most important questions in the treatment of coronary artery disease. The leading North American and European societies largely agree on the current guidelines for the revascularization of unprotected left-main disease (ULMD) and multivessel disease (MVD) which are largely supported by the outcomes of several large randomized trials including SYNTAX, PRECOMBAT, NOBLE, and EXCEL. While these trials are of the highest quality, currently available, they suffer several limitations, including the use of bare metal and/or first-generation drug-eluting stents in early trials and lack of updated surgical outcomes data. The objective of this review is to briefly discuss these key early trials, as well as explore contemporary studies, to provide insight on the current state of coronary revascularization. Evidence suggests that in ULMD and MVD, there are similar mortality rates for CABG and PCI but PCI is associated with fewer "early" strokes, whereas CABG is associated with fewer "late" strokes, myocardial infarctions, and lower need for repeat revascularization. Additionally, studies suggest that CABG remains superior to PCI in patients with intermediate/high SYNTAX scores and in MVD with concomitant proximal left anterior descending (pLAD) artery stenosis. Despite the preceding research and its basis for our current guidelines, there remains significant variation in care that has yet to be quantified. Emerging studies evaluating second-generation drug-eluting stents, specific lesion anatomy, and minimally invasive and hybrid approaches to CABG may lend itself to more individualized patient care.

19.
J Genet Couns ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713948

RESUMO

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder. Aortic dilatation/dissection and ectopia lentis are the most severe features, which affect physical functioning and psychological well-being. In Aboriginal Australians, there is little psychosocial research on genetic conditions. This study explored the physical, psychological, and practical impacts of MFS on Aboriginal Australians. Eighteen (8 affected and 10 unaffected) members of a large Aboriginal Australian family with MFS participated in an ethically approved study. Semi-structured qualitative interviews were conducted, transcribed verbatim, and analyzed thematically. All individuals reported challenges from MFS, negatively affecting day-to-day living. Severe vision impairment was perceived as the greatest challenge, contributing to feelings of stigma and exclusion. With aging, concerns shifted toward cardiac complications. The unpredictability of lens dislocation and aortic dissection was reported to be psychologically challenging. Participants described MFS-related barriers to obtaining and retaining employment, especially following cardiac surgery; with consequential psychological and financial hardships. Participants articulated that their cultural drive to support the ill and respectfully mourn the deceased, regardless of distance, resulted in a significant financial burden. Additionally, when hospitalization and/or funerals occurred, financially solvent individuals were expected to share resources, without any expectation of repayment or reciprocity (i.e., 'demand sharing', common in Aboriginal Australian culture). This study documents the nature and pervasiveness of uncertainty for both affected and unaffected members of an MFS family. Many reported challenges are consistent with other MFS cohorts (including stigma, social exclusion, and unemployment). However, our findings suggest that cultural values may exacerbate the financial costs of MFS for Aboriginal Australians.

20.
Hepatol Commun ; 5(10): 1784-1790, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558832

RESUMO

Current clinical guidelines by both American Association for the Study of Liver Disease and European Association for the Study of the Liver recommend endoscopy in all patients admitted with acute variceal bleeding within 12 hours of admission. Transjugular intrahepatic portosystemic shunt (TIPS) creation may be considered in patients at high risk if hemorrhage cannot be controlled endoscopically. We conducted a cross-sectional observational study to assess how frequently TIPS is created for acute variceal bleeding in the United States without preceding endoscopy. Adult patients undergoing TIPS creation for acute variceal bleeding in the United States (n = 6,297) were identified in the last 10 available years (2007-2016) of the National Inpatient Sample. Hierarchical logistic regression was used to examine the relationship between endoscopy nonutilization and hospital characteristics, controlling for patient demographics, income level, insurance type, and disease severity. Of 6,297 discharges following TIPS creation for acute variceal bleeding in the United States, 31% (n = 1,924) did not receive first-line endoscopy during the same encounter. Rates of "no endoscopy" decreased with increasing population density of the hospital county (nonmicropolitan counties 43%, n = 114; mid-size metropolitan county 35%, n = 513; and central county with >1 million population 23%, n = 527) but not by hospital teaching status (n = 1,465, 32% teaching vs. n = 430, 26% nonteaching; P = 0.10). Higher disease mortality risk (odds ratio, 0.42; 95% confidence interval, 0.22-0.80; P = 0.02) was associated with lower odds of noncompliance. Conclusion: One third of all patients undergoing TIPS creation for acute variceal bleeding in the United States do not receive first-line endoscopy during the same encounter. Patients admitted to urban hospitals are more likely to receive guideline-concordant care.


Assuntos
Endoscopia Gastrointestinal/estatística & dados numéricos , Varizes Esofágicas e Gástricas/cirurgia , Hemorragia Gastrointestinal/cirurgia , Derivação Portossistêmica Transjugular Intra-Hepática/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Varizes Esofágicas e Gástricas/complicações , Feminino , Hemorragia Gastrointestinal/etiologia , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
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