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OBJECTIVE: Patients Acceptable Symptom State (PASS) is a single dichotomized question assessing health satisfaction. We aimed to investigate PASS achievement within 4 weeks of treatment with Janus kinase (JAK) inhibitors (Jakinibs) and its association with treatment response after 4 and 12 weeks in rheumatoid arthritis (RA) patients. METHODS: We recruited consecutive RA patients starting baricitinib or tofacitinib. At baseline, 4 and 12 weeks, we calculated disease activity [Disease Activity Score on 28 joints (DAS28), Clinical Disease Activity Index, Simplified Disease Activity Index], disease status [remission and low-disease activity (LDA)], percentage of patients achieving PASS, and the time to attain PASS. We assessed the impact of clinically relevant variables on PASS achievement by logistic regression analysis. RESULTS: We enrolled 113 patients [98 (86.7%) females; median age 59.6 (interquartile range 16.9), median disease duration 144 (132) months]. 90 (79.6%) patients achieved PASS after 10 (8) days. A similar percentage of PASS achievers and non-achievers was in remission/LDA at weeks 4 and 12, but the reduction of disease activity was significantly greater in PASS achievers. All patients achieving Boolean remission at weeks 4 and 12 had achieved PASS within 4 weeks. The impact of Patients Global Assessment (PGA) on DAS28 was significantly greater in PASS non-achievers compared to PASS achievers; inversely, the impact of C-reactive protein was more relevant in PASS achievers. At multivariate analysis, pain and PGA were significantly associated with PASS. CONCLUSIONS: In our cohort, Jakinibs allowed an early achievement of PASS in a great percentage of RA patients. PASS is strictly dependent on PGA and pain and could suggest, early in the management of RA patients, therapeutic success.
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OBJECTIVE: Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. METHODS: This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. RESULTS: This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). CONCLUSIONS: Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.
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Abatacepte , Antirreumáticos , Artrite Reumatoide , Humanos , Abatacepte/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Masculino , Feminino , Estudos Retrospectivos , Idoso , Antirreumáticos/uso terapêutico , Pessoa de Meia-Idade , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Resultado do Tratamento , Estimativa de Kaplan-Meier , Quimioterapia Combinada , Estudos de CoortesRESUMO
BACKGROUND: It is a common opinion that Primary Sjögren Syndrome (pSS) damages the exocrine glands and determines the reduction of secreted saliva, some studies show that there are qualitative anomalies of the mucins produced in saliva, including MUC7, MUC5B, MUC1. The purpose of this study is to trace all the information useful to establish whether there is a qualitative or quantitative defect of the mucins in the pSS. MATERIAL AND METHODS: We reviewed the literature by looking for publications relevant to the topic in electronic databases. Sixteen articles met the search criteria. The studies were divided into two categories, those that studied the rheological characteristics of the saliva and those that studied the structural and / or metabolism modifications of the muciparous cells in the salivary glands. RESULTS: in Patients with pSS, xerostomia and the reduction of salivary spinnbarkeit are only partially related to the reduction of the unstimulated salivary flow. In pSS, pathological alterations of mucins' chemical-physical properties prevail as a cause of the clinical characteristics. Moreover, in pSS there are structural and metabolism changes in salivary glands' muciparous cells. CONCLUSIONS: There is much evidence that supports the presence of qualitative alterations in the saliva's rheological properties in Patients with pSS, and these are the main cause, more than the reduction of the unstimulated salivary flow, of the disease clinical characteristics - dry mouth and complications in the oral cavity. Therefore we propose to add to the classification criteria of pSS also a qualitative test of salivary glycoproteins.
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Síndrome de Sjogren , Xerostomia , Humanos , Mucinas , Saliva , Glândulas Salivares , Síndrome de Sjogren/complicaçõesRESUMO
Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren's syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P = 0.02, OR = 1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P = 0.03, OR = 1.53), pSS (P = 0.016, OR = 1.69), and RA (P = 0.0001, OR = 2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.
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Doenças Autoimunes/diagnóstico , Doenças Autoimunes/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Alelos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos , Itália , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/genética , Fenótipo , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/genéticaRESUMO
Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case-control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.
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Artrite Reumatoide/imunologia , Infecções por Bacteroidaceae/imunologia , Microbiota/imunologia , Periodontite/imunologia , Porphyromonas gingivalis/fisiologia , Língua/patologia , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Infecções por Bacteroidaceae/epidemiologia , Biofilmes , Estudos de Casos e Controles , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Língua/microbiologiaRESUMO
The aim of this study was to investigate the expression of the interleukin (IL)-36 axis in patients with primary Sjögren's syndrome (pSS). Blood and minor labial salivary glands (MSG) biopsies were obtained from 35 pSS and 20 non-Sjögren's syndrome patients (nSS) patients. Serum IL-36α was assayed by enzyme-linked immunosorbent assay (ELISA). IL-36α, IL-36R, IL-36RA, IL-38, IL-22, IL-17, IL-23p19 and expression in MSGs was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and tissue IL-36α and IL-38 expression was also investigated by immunohistochemistry (IHC). αß and γδ T cells and CD68(+) cells isolated from MSGs were also studied by flow cytometry and confocal microscopy analysis. IL-36α was over-expressed significantly in the serum and in the salivary glands of pSS. Salivary gland IL-36α expression was correlated with the expression levels of IL-17, IL-22 and IL-23p19. IL-38, that acts as inhibitor of IL-36α, was also up-regulated in pSS. αß(+) CD3(+) T cells and CD68(+) cells were the major source of IL-36α in minor salivary glands of pSS. γδ T cells were not significantly expanded in the salivary glands of pSS but produced more IL-17, as their percentage correlated with the focus score. Higher expression of IL-36α and IL-36R was also demonstrated in γδ T cells isolated from pSS compared to controls. In this study we demonstrate that a significant increase in circulating and tissue levels of IL-36α occurs in pSS patients.
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Interleucina-1/imunologia , Receptores de Interleucina/imunologia , Glândulas Salivares/imunologia , Síndrome de Sjogren/imunologia , Linfócitos T/imunologia , Adulto , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos de Diferenciação Mielomonocítica/imunologia , Estudos de Casos e Controles , Feminino , Regulação da Expressão Gênica , Humanos , Interleucina-1/genética , Interleucina-17/genética , Interleucina-17/imunologia , Subunidade p19 da Interleucina-23/genética , Subunidade p19 da Interleucina-23/imunologia , Interleucinas/genética , Interleucinas/imunologia , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Receptores de Interleucina/genética , Glândulas Salivares/patologia , Transdução de Sinais , Síndrome de Sjogren/genética , Síndrome de Sjogren/patologia , Linfócitos T/patologia , Interleucina 22RESUMO
OBJECTIVE: Systemic autoimmune diseases, in particular systemic lupus erythematosus and rheumatoid arthritis, are characterized by a high risk of premature cardiovascular (CV) events. Disease-related characteristics and traditional CV disease risk factors may contribute to atherosclerotic damage. However, there are limited data on the risk of overt CV events in primary Sjögren's syndrome (pSS). METHODS: We retrospectively analysed a cohort of patients with 1343 pSS. Disease-related clinical and laboratory data, traditional CV disease risk factors and overt CV events were recorded. Prevalence of traditional CV disease risk factors and of major CV events was compared between a subgroup of 788 female patients with pSS aged from 35 to 74 years and 4774 age-matched healthy women. RESULTS: Hypertension and hypercholesterolaemia were more prevalent, whereas smoking, obesity and diabetes mellitus were less prevalent, in women with pSS than in control subjects. Cerebrovascular events (2.5% vs. 1.4%, P = 0.005) and myocardial infarction (MI) (1.0% vs. 0.4%, P = 0.002) were more common in patients with pSS. In the whole population, central nervous system involvement (odds ratio (OR) 5.6, 95% confidence interval (CI) 1.35-23.7, P = 0.02) and use of immunosuppressive therapy (OR 1.9, 95% CI 1.04-3.70, P = 0.04) were associated with a higher risk of CV events. Patients with leucopenia had a higher risk of angina (P = 0.01). CONCLUSIONS: pSS is associated with an increased risk of cerebrovascular events and MI. Disease-related clinical and immunological markers may have a role in promoting CV events.
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Doenças Cardiovasculares/epidemiologia , Medição de Risco/métodos , Síndrome de Sjogren/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Síndrome de Sjogren/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: To determine the clinical and laboratory differences between cryoglobulinaemic and hypergammaglobulinaemic purpura in primary Sjögren's syndrome (pSS), in a large Italian multicentre cohort. METHOD: Patients were selected according to the following criteria: fulfilling the American-European classification criteria for pSS, serum cryoglobulin and gammaglobulin levels evaluated, and lack of hepatitis C virus (HCV) infection. Multinomial analyses were performed by distinguishing three groups of pSS: (i) purpura associated with cryoglobulinaemic vasculitis (CV), (ii) purpura associated with hypergammaglobulinaemic vasculitis (HGV), and (iii) pSS patients without purpura (pSS controls). Patients with purpura but without cryoglobulins or hypergammaglobulinaemia were excluded. RESULTS: A total of 652 patients were enrolled in this study. Group 1/CV comprised 23/652 patients (3.53%), group 2/HGV 40/652 patients (6.13%), and group 3/pSS controls 589/652 (90.34%). The three groups were found to be significantly different from each other (post-estimation test: group 1/CV vs. group 3/pSS controls: p < 0.0001; group 1/CV vs. group 2/HGV: p = 0.0001; group 2/HGV vs. group 3/pSS controls: p = 0.0003), thus confirming the different phenotypes of purpura in pSS.Multivariate analyses revealed that peripheral neuropathy (p < 0.001), low C4 (p < 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.02), and the presence of anti-SSB/La antibodies (p = 0.02) characterized CV whereas rheumatoid factor (p = 0.001), leucopaenia (p = 0.01), serum monoclonal component (p = 0.01), and anti-SSA/Ro antibodies (p = 0.049) were significantly associated with HGV. Lymphoma was associated only with CV. CONCLUSIONS: HGV is a cutaneous vasculitis, related to a benign B-cell proliferation, whereas CV is a systemic immune complex-mediated vasculitis with complement activation and a higher risk of lymphoma, thus confirming CV but not HGV as a prelymphomatous condition in pSS.
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Crioglobulinemia/imunologia , Púrpura Hiperglobulinêmica/imunologia , Síndrome de Sjogren/imunologia , Adulto , Complexo Antígeno-Anticorpo/imunologia , Linfócitos B/imunologia , Estudos Transversais , Crioglobulinemia/sangue , Feminino , Humanos , Itália , Linfoma/sangue , Linfoma/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/imunologia , Prognóstico , Púrpura Hiperglobulinêmica/sangue , Estudos Retrospectivos , Síndrome de Sjogren/sangue , Vasculite/sangue , Vasculite/imunologiaRESUMO
OBJECTIVE: The objective of this report is to investigate the prognostic value of minor salivary glands (MSG) assessment, routinely performed with hematoxilin-eosin (H&E) staining, for the diagnosis of primary Sjögren's syndrome (pSS). METHODS: We retrospectively evaluated clinical, serological and histological features of 794 pSS patients. H&E-stained sections were assessed using the Chisholm and Mason grading system and/or the focus score (FS). RESULTS: FS allowed the identification of a number of differences in the disease spectrum, and its prognostic role was further confirmed by quantifying the association between FS value and clinical/serological variables with binary logistic regression. Moreover, hypocomplementemia and FS resulted the only variables associated with lymphoma at univariate analysis, and FS appeared to be associated with lymphoma independently on complement fraction concentrations. Conversely, when patients were divided according to the Chisholm and Mason grading system, we failed to observe any significant difference between subgroups. CONCLUSION: In addition to its diagnostic role, our data seem to support that the routine assessment of MSG-FS with H&E staining is useful to predict at the time of diagnosis the adverse outcomes, such as lymphoma and extraglandular manifestations, that complicate the pSS course. On this basis, it should be recommended that an MSG biopsy be performed even in those patients displaying clinical and serological criteria, allowing the diagnosis of pSS independent of histological status.
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Glândulas Salivares/patologia , Síndrome de Sjogren/patologia , Estudos Transversais , Amarelo de Eosina-(YS) , Feminino , Hematoxilina , Humanos , Masculino , Análise Multivariada , Prognóstico , Estudos RetrospectivosRESUMO
Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is reported in about 50% of patients. Among the neuropsychiatric features of SLE, myelopathy, including acute transverse myelitis (ATM) or acute longitudinal myelitis (ALM), represents an uncommon event. A possible vascular aetiology of SLE myelopathies has been hypothesized and it seems to be much more associated to SLE-associated antiphospholipid syndrome (APS). Furthermore, a possible infectious cause of ATM or ALM in healthy subjects has been described. SLE patients are susceptible to infection due to the disease itself or to the immunosuppressive therapy. Cryptococci non-neoformans have been rarely associated to infections in humans. Here we describe the case of a 47-year-old woman with SLE and Sjögren Syndrome who developed an ALM concurrently with a Cryptococcus laurentii pneumonia. The patient was treated with antimycotics, high doses of glucocorticoids and intravenous immunoglobulins with a significant clinical and radiological improvement. As far as we know, this is the first case of Cryptococcus laurentii infection and ALM in a patient with SLE who later developed a seronegative APS. Even though myelopathy may be considered primarily associated to SLE, a possible role of the infection in ALM development cannot be excluded.
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Criptococose/complicações , Lúpus Eritematoso Sistêmico/complicações , Mielite/etiologia , Doença Aguda , Criptococose/microbiologia , Cryptococcus/classificação , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mielite/tratamento farmacológico , Pneumonia/microbiologia , Síndrome de Sjogren/complicaçõesRESUMO
Ferritin has a key role in Adult-onset Still's disease (AOSD). Its production seems related to macrophage activation of which sCD163 is a major serum marker. Thus, we aimed at evaluating the role of sCD163 in AOSD and its relationship with ferritin. Furthermore, we determined the expression of CD163 and ferritin in a lymph-node from an AOSD patient. sCD163 and serum ferritin were measured in 34 patients with AOSD (21 active, 13 non-active), 18 sepsis and 22 healthy controls (HC). Immunohistology was performed on a lymph-node from an AOSD patient in order to detect CD163 and ferritin. A tonsil from an HC was used as control. Mean sCD163 (8.6 ± 5.4 mg/L) was higher in active AOSD than "non-active" patients (4.6 ± 2.7 mg/L, p = 0.02). The mean sCD163 in AOSD (6.9 ± 4.9 mg/L) and sepsis (7.1 ± 5.6 mg/L) were higher than in HC (2.56 ± 1.17 mg/L, p < 0.001), but no difference between AOSD and sepsis was detected. sCD163 positively correlated with ferritin (p = 0.0045; r = 0.4755) only in AOSD. Serum ferritin (mean 3,640.1 ± 6,896.9 µg/L) was higher in active AOSD than in sepsis (1,720.2 ± 3,882.1 µg/L, p < 0.007). CD163 was equally distributed in the B and T areas of both lymph-node and tonsil. Differently from the tonsil, ferritin was expressed only in the lymph-node B area. sCD163 is a marker of disease activity in AOSD. The correlation with ferritin may lead to hypothesize a macrophage activation related to hyperferritinemia. Ferritin was found expressed only in the B area of the AOSD lymph-node, suggesting a role for this molecule as an antigen in the disease pathogenesis.
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Antígenos CD/sangue , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/imunologia , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/imunologia , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/imunologia , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Ferritinas/sangue , Humanos , Linfonodos/imunologia , Linfonodos/metabolismo , Linfonodos/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Tonsila Palatina/imunologia , Tonsila Palatina/metabolismo , Tonsila Palatina/patologia , Sepse/complicações , Doença de Still de Início Tardio/complicações , Adulto JovemRESUMO
Recently, a new syndrome, namely the "Autoimmune/inflammatory syndrome induced by adjuvants" (ASIA) has been defined. In this syndrome different conditions characterized by common signs and symptoms and induced by the presence of an adjuvant are included. The adjuvant is a substance capable of boosting the immune response and of acting as a trigger in the development of autoimmune diseases. Post-vaccination autoimmune phenomena represent a major issue of ASIA. Indeed, despite vaccines represent a mainstay in the improvement of human health, several of these have been implicated as a potential trigger for autoimmune diseases. Sjogren's Syndrome (SjS) is a systemic chronic autoimmune inflammatory disease characterized by the presence of an inflammatory involvement of exocrine glands accompanied by systemic manifestations. Own to the straight association between infectious agents exposure (mainly viruses) and sicca syndrome development, the possible link between vaccine and SjS is not surprising. Indeed, a few cases of SjS following vaccine delivery have been reported. At the same extent, the induction of SjS following silicone exposure has been described too. Thus, the aim of this review was to focus on SjS and its possible development following vaccine or silicone exposure in order to define another possible facet of the ASIA syndrome.
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Adjuvantes Imunológicos/efeitos adversos , Doenças Autoimunes/etiologia , Inflamação/etiologia , Síndrome de Sjogren/etiologia , Animais , Autoimunidade , Humanos , SíndromeRESUMO
BACKGROUND: Superimposed high-frequency jet ventilation (SHFJV) has proved to be safe and effective in clinical practice. However, it is unclear which frequency range optimizes ventilation and gas exchange. The aim of this study was to systematically compare high-frequency jet ventilation (HFJV) with HFJV by assessing chest wall volume variations (ΔEEV(CW)) and gas exchange in relation to variable high frequency. METHODS: SHFJV or HFJV were used alternatively to ventilate the lungs of 10 anaesthetized pigs (21-25 kg). The low-frequency component was kept at 16 min(-1) in SHFJV. In both modes, high frequencies ranging from 100 to 1000 min(-1) were applied in random order and ventilation was maintained for 5 min in all modalities. Chest wall volume variations were obtained using opto-electronic plethysmography. Airway pressures and arterial blood gases were measured repeatedly. RESULTS: SHFJV increased ΔEEV(CW) compared with HFJV; the difference ranged from 43 to 68 ml. Tidal volume (V(T)) was always >240 ml during SHFJV whereas during HFJV ranged from 92 ml at the ventilation frequency of 100 min(-1) to negligible values at frequencies >300 min(-1). We observed similar patterns for Pa(O2) and Pa(CO2). SHFJV provided generally higher, frequency-independent oxygenation (Pa(O2) at least 32.0 kPa) and CO2 removal (Pa(CO2) â¼5.5 kPa), whereas HFJV led to hypoxia and hypercarbia at higher rates (Pa(O2) <10 kPa and Pa(CO2)>10 kPa at f(HF)>300 min(-1)). CONCLUSIONS: In a porcine model, SHFJV was more effective in increasing end-expiratory volume than single-frequency HFJV, but both modes may provide adequate ventilation in the absence of airway obstruction and respiratory disease, except for HFJV at frequencies ≥300 min(-1).
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Ventilação em Jatos de Alta Frequência , Medidas de Volume Pulmonar , Troca Gasosa Pulmonar , Animais , Modelos Animais , SuínosRESUMO
PURPOSE: The rationale for the present study was to evaluate the predictive role of (99m)Tc-infliximab scintigraphy in therapy decision-making in patients with refractory monoarthritis and also candidates for intraarticular (IA) infliximab treatment. METHODS: We studied 12 patients (5 with rheumatoid arthritis and 7 with spondyloarthropathy) with active monoarthritis (11 knees and 1 ankle) that had lasted for at least 3 months. Patients were evaluated clinically and ultrasonographically at baseline and 12 weeks after IA administration of infliximab. At the same time-points, (99m)Tc-infliximab scintigraphy was performed: planar anterior and posterior images of arthritic joints were acquired at 6 and 20 h after injection and target-to-background (T/B) ratios were calculated. RESULTS: After treatment, a significant improvement in clinical and ultrasonographic parameters was recorded in six patients. Three patients had a partial response and three did not respond. Regarding scintigraphic evaluation, the T/B ratio analysis showed a significantly higher uptake in affected than in nonaffected joints before therapy (1.78 ± 0.46 vs. 1.29 ± 0.27, p = 0.006 at 6 h; 2.05 ± 0.50 vs. 1.41 ± 0.36 at 20 h, p = 0.002), and mean uptake at 20 h was also significantly higher than at 6 h (p = 0.0004). Scintigraphy showed a significant decrease in posttherapy T/B ratios of the affected joints (p = 0.0001 at 6 h and p = 0.0001 at 20 h), indicating a reduction in TNF into the affected joints. Most importantly, responders showed a significantly higher percentage increase in pretherapy uptake from 6 h to 20 h in the affected joints than nonresponders (p = 0.00001). CONCLUSION: The results of the present investigation suggest that (99m)Tc-infliximab scintigraphy could be a useful tool to predict the clinical response to IA infliximab treatment in patients with refractory monoarthritis.
Assuntos
Anticorpos Monoclonais , Artrite/diagnóstico por imagem , Artrite/terapia , Resistência a Medicamentos , Articulações , Compostos de Organotecnécio , Adulto , Artrite/tratamento farmacológico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/terapia , Tomada de Decisões , Feminino , Humanos , Infliximab , Masculino , Cintilografia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , UltrassonografiaRESUMO
BACKGROUND: New ventilators have simplified the use of supraglottic superimposed high-frequency jet ventilation (SHFJV(SG)), but it has not been systematically compared with other modes of jet ventilation (JV) in humans. We sought to investigate whether SHFJV(SG) would provide more effective ventilation compared with single-frequency JV techniques. METHODS: A total of 16 patients undergoing minor laryngeal surgery under general anaesthesia were included. In each patient, four different JV techniques were applied in random order for 10-min periods: SHFJV(SG), supraglottic normal frequency (NFJV(SG)), supraglottic high frequency (HFJV(SG)), and infraglottic high-frequency jet ventilation (HFJV(IG)). Chest wall volume variations were continuously measured with opto-electronic plethysmography (OEP), intratracheal pressure was recorded and blood gases were measured. RESULTS: Chest wall volumes were normalized to NFJV(SG) end-expiratory level. The increase in end-expiratory chest wall volume (EEV(CW)) was 239 (196) ml during SHFJV(SG) (P<0.05 compared with NFJV(SG)). EEV(CW) was 148 (145) and 44 (106) ml during HFJV(SG) and HFJV(IG), respectively (P<0.05 compared with SHFJV(SG)). Tidal volume (V(T)) during SHFJV(SG) was 269 (149) ml. V(T) was 229 (169) ml (P=1.00 compared with SHFJV(SG)), 145 (50) ml (P<0.05), and 110 (33) ml (P<0.01) during NFJV(SG), HFJV(SG), and HFJV(IG), respectively. Intratracheal pressures corresponded well to changes in both EEV(CW) and V(T). All JV modes resulted in adequate oxygenation. However, was lowest during HFJV(SG) [4.3 (1.3) kPa; P<0.01 compared with SHFJV(SG)]. CONCLUSION: SHFJV(SG) was associated with increased EEV(CW) and V(T) compared with the three other investigated JV modes. All four modes provided adequate ventilation and oxygenation, and thus can be used for uncomplicated laryngeal surgery in healthy patients with limited airway obstruction.
Assuntos
Ventilação em Jatos de Alta Frequência/métodos , Laringoscopia/métodos , Laringe/cirurgia , Adulto , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/métodos , Volume de Ventilação PulmonarRESUMO
More than two third of patients with primary Sjögren's syndrome (SS) report fatigue. Despite its clinical relevance, only a few studies have examined the relationship of fatigue with the presence of an overlapping Fibromyalgia (FM) and other clinical and biological variables. The aim of this study was to assess the relationship between fatigue and SS disease activity and damage, FM, widespread pain, and mood disorders; finally, the possible correlation between fatigue and a panel of cytokines likely to drive the immunopathological process of the disease has been examined. Thirty-five female patients with primary SS were consecutively enrolled; for each patient the Sjögren's Syndrome Disease Damage Index (SSDDI) and the Sjögren's Syndrome Disease Activity Index (SSDAI) were calculated. Patients rated pain, fatigue and disease activity using a 100-mm VAS and completed Health Assessment Questionnaire (HAQ), the Zung depression (ZSDS) and anxiety scales (ZSAS). 30/35 patients (85.7%) felt unduly tired and the same percentage of patients suffered with pain in more than one area of the body. 7 patients satisfied ACR criteria for FM, representing 20% of the whole cohort and 23% of SS patients with fatigue. No differences were found in disease duration, SSDDI, SSDAI, ZSDS and ZSAS among SS patient with or without FM. In the whole group, fatigue VAS correlated with HAQ, ZSAS, ZSDS and pain VAS but not with age, disease duration, presence and severity of arthritis, SSDDI, SSDAI, or cytokines. In conclusion, an overlapping FM can contribute to, but does not entirely account for fatigue in Italian patients with primary SS.