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Adult-onset still's disease is a rare condition that is generally treated by glucocorticoids. Importantly, due to the limited established treatments, glucocorticoid-refractory cases are particularly difficult to treat. Between December 2009 and August 2022, nine patients with adult-onset Still's disease were treated with tocilizumab (tocilizumab group). The therapeutic efficacy and safety of tocilizumab initiation in the acute phase were evaluated in cases of initial onset and recurrence. We also compared the efficacy of tocilizumab with that of methotrexate (methotrexate group, n = 13), which has been the drug of choice for adjunctive therapy. Tocilizumab demonstrated the expected efficacy in all four patients who received it at relapse and in three of the five patients who received it at the initial onset. However, two patients developed macrophage activation syndrome following treatment. A comparison of treatment effects between the methotrexate and tocilizumab groups revealed that the ferritin and C-reactive protein levels, severity score, and glucocorticoid doses decreased over time in both groups; nonetheless, the tocilizumab group experienced a more stable effect. Tocilizumab is undoubtedly a valuable treatment option for adult-onset Still's disease, especially when administered at relapse. This suggests that it shows both high safety and good efficacy. Nevertheless, a larger sample size is required to validate the efficacy and safety of tocilizumab compared with those of the existing alternatives. Key Points ⢠We examined the significance of TCZ in terms of therapeutic efficacy, reduction in glucocorticoid usage, and safety in patients with AOSD. ⢠We compared the therapeutic efficacy of TCZ with that of MTX, which is often used to treat glucocorticoid-resistant AOSD. ⢠TCZ is undoubtedly a valuable treatment option for AOSD, especially when administered at relapse, suggesting both high safety and good efficacy.
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Anticuerpos Monoclonales Humanizados , Metotrexato , Enfermedad de Still del Adulto , Adulto , Humanos , Metotrexato/uso terapéutico , Glucocorticoides/uso terapéutico , Enfermedad de Still del Adulto/tratamiento farmacológico , Resultado del Tratamiento , RecurrenciaRESUMEN
Lysine-specific demethylase 1 (LSD1) is an enzyme that demethylates methylated histone H3 lysine 4 (H3K4). Inhibition of LSD1 enzyme activity could increase H3K4 methylation levels and treat diseases associated with epigenetic dysregulation. However, known LSD1 inhibitors disrupt the interaction between LSD1 and cofactors such as GFI1B, causing the risk of hematological toxicity, including thrombocytopenia. Starting from a known LSD1 inhibitor (±)1 as a lead compound, a novel series of LSD1 inhibitors that do not induce the expression of GFI1 mRNA, an in vitro surrogate marker of LSD1-GFI1B dissociation, has been designed and synthesized. Initial structure-activity relationship (SAR) studies revealed the structural features key to avoiding GFI1 mRNA induction. Such SAR information enables optimization of LSD1 inhibitors with lowered risk of hematological side effects; TAK-418 ((1R,2R)-2n), the clinical candidate compound found through this optimization, has a hematological safety profile in rodents and humans. We further confirmed that oral administration of TAK-418 at 0.3 and 1 mg/kg for 2 weeks ameliorated memory deficits in mice with NMDA receptor hypofunction, suggesting potential of efficacy in neurodevelopmental disorders. TAK-418 warrants further investigation as a novel class of LSD1 inhibitors with a superior safety profile for the treatment of CNS disorders.
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Histona Demetilasas , Lisina , Animales , Inhibidores Enzimáticos/química , Lisina/metabolismo , Ratones , ARN Mensajero , Relación Estructura-ActividadRESUMEN
Systemic lupus erythematosus (SLE) is a chronic inflammatory and representative autoimmune disease. Extremely complicated and multifactorial interactions between various genetic factors and individual susceptibility to environmental factors are involved in the pathogenesis of SLE. Several studies have reported that mutation and activation of toll-like receptor (TLR) 7 are involved in the onset of autoimmunity, including SLE. Thus, we investigated the response of SLE-prone mice to continuous environmental factors, particularly TLR7 agonist exposure, and changes in their phenotypes. Female and male NZBWF1 (BWF1) mice were treated from 20 weeks of age with a TLR7 agonist, imiquimod (IMQ), 3 times weekly for up to 12 weeks. IMQ-exposed female BWF1 mice showed worsened lupus nephritis. However, autoantibody production was not enhanced in IMQ-exposed female BWF1 mice. The Th1 cytokine expression was upregulated in the kidney of IMQ-treated mice. In IMQ-exposed BWF1 mice, neutralization of IFN-γ suppressed early-phase lupus nephritis. Additionally, in male BWF1 mice IMQ exposure induced minor aggravation of lupus nephritis. These results suggest that the induction of aggravated lupus nephritis by TLR7 agonist exposure was related to the expression of IFN-γ via acute TLR7 signal-induced renal inflammation, and that the involvement of genetic factors associated with a predisposition to SLE is also essential. Thus, the activation of TLR7 signaling by exposure to environmental factors may upset the balance of factors that maintain SLE remission. We hypothesize that the inhibition of TLR7 signaling and IFN-γ signaling is effective for preventing the onset and flare and maintaining remission of lupus nephritis.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Ratones , Masculino , Femenino , Animales , Imiquimod , Receptor Toll-Like 7/metabolismo , Nefritis Lúpica/tratamiento farmacológico , Autoinmunidad , Transducción de SeñalRESUMEN
BACKGROUND: Recent increased use of medical images induces further burden of their interpretation for physicians. A plain X-ray is a low-cost examination that has low-dose radiation exposure and high availability, although diagnosing urolithiasis using this method is not always easy. Since the advent of a convolutional neural network via deep learning in the 2000s, computer-aided diagnosis (CAD) has had a great impact on automatic image analysis in the urological field. The objective of our study was to develop a CAD system with deep learning architecture to detect urinary tract stones on a plain X-ray and to evaluate the model's accuracy. METHODS: We collected plain X-ray images of 1017 patients with a radio-opaque upper urinary tract stone. X-ray images (n = 827 and 190) were used as the training and test data, respectively. We used a 17-layer Residual Network as a convolutional neural network architecture for patch-wise training. The training data were repeatedly used until the best model accuracy was achieved within 300 runs. The F score, which is a harmonic mean of the sensitivity and positive predictive value (PPV) and represents the balance of the accuracy, was measured to evaluate the model's accuracy. RESULTS: Using deep learning, we developed a CAD model that needed 110 ms to provide an answer for each X-ray image. The best F score was 0.752, and the sensitivity and PPV were 0.872 and 0.662, respectively. When limited to a proximal ureter stone, the sensitivity and PPV were 0.925 and 0.876, respectively, and they were the lowest at mid-ureter. CONCLUSION: CAD of a plain X-ray may be a promising method to detect radio-opaque urinary tract stones with satisfactory sensitivity although the PPV could still be improved. The CAD model detects urinary tract stones quickly and automatically and has the potential to become a helpful screening modality especially for primary care physicians for diagnosing urolithiasis. Further study using a higher volume of data would improve the diagnostic performance of CAD models to detect urinary tract stones on a plain X-ray.
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Aprendizaje Profundo , Diagnóstico por Computador , Redes Neurales de la Computación , Radiografía , Cálculos Urinarios/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Conjuntos de Datos como Asunto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Interpretación de Imagen Radiográfica Asistida por Computador , Sensibilidad y EspecificidadRESUMEN
Anti-MDA5 antibody-positive clinically amyopathic dermatomyositis (CADM) is often complicated by rapidly progressive interstitial lung disease and is associated with poor prognosis. However, even though recurrence is reported to be infrequent if successful medical treatment is administered, the long-term prognosis remains unclear. In this case report, we examined the clinical features and treatment details of three patients with anti-MDA5 antibody-positive CADM with multiple recurrences during long-term survival at Juntendo University Urayasu Hospital. Of the three patients, two failed to convert to an anti-MDA5 antibody-negative status, and one patient died. One of the remaining patients experienced two relapses but eventually tested negative for anti-MDA5 antibodies and showed a relatively stable clinical course. Although cases of recurring anti-MDA5 antibody-positive CADM rarely occur, they may occasionally be fatal. The prognosis for anti-MDA5 antibody-positive CADM has improved over time owing to its establishment as a disease. However, further information and research is necessary to ascertain its long-term prognosis.
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Dermatomiositis , Autoanticuerpos/aislamiento & purificación , Dermatomiositis/diagnóstico , Humanos , Helicasa Inducida por Interferón IFIH1/inmunología , Recurrencia , SobrevivientesRESUMEN
OBJECTIVES: Metformin is a known therapeutic agent for diabetes. Recently, several reports suggested the possibility of improvement in autoimmune disease and malignancy conditions through the effect of metformin on the immune system. Although there have been reports on the therapeutic effects of metformin on mouse models of collagen-induced arthritis, simulating human rheumatoid arthritis (RA), the effect of metformin on human RA remains unknown. Therefore, we investigated the inhibitory effect of metformin on the pathogenesis of human RA in vitro. METHODS: Osteoclastogenesis was evaluated with or without metformin. through tartrate-resistant acid phosphatase staining, osteoclast-specific enzyme expression analysis, and a bone resorption assay. Human fibroblast-like synoviocyte MH7A cells were stimulated with TNF-α, and the expression of proinflammatory cytokines and protease and growth factor genes was evaluated with or without metformin. Metformin has been used to evaluate their potential modulatory effects on cells treated with TNF-α. Moreover, we examined angiogenesis by performing a tube formation assay using human umbilical vein endothelial cells (HUVECs) with or without metformin. RESULTS: Osteoclastogenesis was suppressed in the presence of metformin, and the expression of osteoclast-specific genes was reduced. The TNF-α-induced expression of inflammatory cytokines and protease and growth factor genes in MH7A cells was downregulated by metformin. Additionally, the induced formation of tubular networks in HUVECs was also disrupted following treatment with metformin. CONCLUSIONS: These results suggest that metformin might improve the pathogenesis of RA, including joint inflammation and destruction. Thus, metformin might be utilised as a potential therapeutic agent in the treatment of RA.
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Artritis Experimental , Artritis Reumatoide , Metformina , Animales , Artritis Reumatoide/tratamiento farmacológico , Células Cultivadas , Células Endoteliales , Metformina/farmacología , Osteoclastos , Membrana SinovialRESUMEN
DNA methylation is an epigenetic modification that regulates gene transcription. DNA methyltransferase 1 (DNMT1) plays an important role in DNA methylation. However, the involvement of DNMT1 and DNA methylation in the pathogenesis of atopic dermatitis (AD) remains unclear. In this study, microarray analysis revealed that peripheral blood mononuclear cells of AD patients with low DNMT1 expression (DNMT1-low) highly expressed dendritic cell (DC) activation-related genes. Also, DNMT1-low AD patients exhibited a higher itch score compared to AD patients with high DNMT1 expression (DNMT1-high). By using an AD-like mouse model induced by the application of Dermatophagoides farinae body ointment, we found that Dnmt1 expression was decreased, while the expression of C-C chemokine receptor type 7 (Ccr7) was upregulated in mouse skin DCs. Furthermore, mice exposed to social defeat stress exhibited Dnmt1 downregulation and Ccr7 upregulation in skin DCs. Additionally, dermatitis and itch-related scratching behavior were exacerbated in AD mice exposed to stress. The relationship between low DNMT1 and itch induction was found in both human AD patients and AD mice. In mouse bone marrow-derived DCs, Ccr7 expression was inhibited by 5-aza-2-deoxycytidine, a methylation inhibitor. Furthermore, in mouse skin DCs, methylation of CpG sites in Ccr7 was modified by either AD induction or social defeat stress. Collectively, these findings suggest that social defeat stress exacerbates AD pathology through Dnmt1 downregulation and Ccr7 upregulation in mouse skin DCs. The data also suggest a role of DNMT1 downregulation in the exacerbation of AD pathology.
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ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Células Dendríticas/metabolismo , Dermatitis Atópica/enzimología , Regulación hacia Abajo , Receptores CCR7/genética , Derrota Social , Estrés Psicológico/enzimología , Regulación hacia Arriba , Adulto , Anciano , Anciano de 80 o más Años , Animales , Metilación de ADN , Dermatitis Atópica/sangre , Dermatitis Atópica/genética , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Prurito/sangre , Prurito/patología , Receptores CCR7/metabolismo , Piel/patología , Estrés Psicológico/sangreRESUMEN
We herein report a rare case of nontraumatic urethral rupture. The patient presented with oliguria, perineal pain and anorexia, and a 3 cm fistula was located in the perineum. Computed tomography revealed a retroperitoneal abscess invading the urethra, and a retrograde urethrogram revealed the rupture of the membranous urethra. He had no history of perineum trauma or transurethral procedures. Although he underwent a suprapubic cystostomy and conservative therapy by antibiotics, he eventually died.
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We identified novel potent inhibitors of p38 mitogen-activated protein (MAP) kinase using a structure-based design strategy, beginning with lead compound, 3-(butan-2-yl)-6-(2,4-difluoroanilino)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (1). To enhance the inhibitory activity of 1 against production of tumor necrosis factor-α (TNF-α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5-b]pyridin-2-one core was successfully linked with the p-methylbenzamide fragment. Among the compounds evaluated, 3-(3-tert-butyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)-4-methyl-N-(1-methyl-1H-pyrazol-3-yl)benzamide (25) exhibited potent p38 inhibition, superior suppression of TNF-α production in hWB cells, and also significant inâ vivo efficacy in a rat model of collagen-induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors.
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Artritis Experimental/tratamiento farmacológico , Diseño de Fármacos , Imidazoles/farmacología , Piridinas/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Artritis Experimental/inducido químicamente , Línea Celular , Colágeno , Cristalografía por Rayos X , Modelos Animales de Enfermedad , Humanos , Imidazoles/síntesis química , Imidazoles/química , Modelos Moleculares , Estructura Molecular , Piridinas/síntesis química , Piridinas/química , Ratas , Factor de Necrosis Tumoral alfa/biosíntesis , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
We identified a lead series of p38 mitogen-activated protein kinase inhibitors using a structure-based design strategy from high-throughput screening of hit compound 1. X-ray crystallography of 1 with the kinase showed an infrequent flip of the peptide bond between Met109 and Gly110, which was considered to lead to high kinase selectivity. Our structure-based design strategy was to conduct scaffold transformation of 1 with maintenance of hydrogen bond interactions with the flipped hinge backbone of the enzyme. In accordance with this strategy, we focused on scaffold transformation to identify imidazo[4,5-b]pyridin-2-one derivatives as potent inhibitors of the p38 MAP kinase. Of the compounds evaluated, 21 was found to be a potent inhibitor of the p38 MAP kinase, lipopolysaccharide-induced tumor necrosis factor-α (TNF-α) production in human monocytic leukemia cells, and TNF-α-induced production of interleukin-8 in human whole blood cells. Herein we describe the discovery of potent and orally bioavailable imidazo[4,5-b]pyridin-2-one-based p38 MAP kinase inhibitors that suppressed cytokine production in a human whole blood cell-based assay.
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Antineoplásicos/química , Imidazoles/química , Inhibidores de Proteínas Quinasas/química , Piridinas/química , Piridonas/química , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacocinética , Células Sanguíneas , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Enlace de Hidrógeno , Imidazoles/síntesis química , Imidazoles/farmacocinética , Interleucina-8/metabolismo , Lipopolisacáridos/química , Modelos Moleculares , Estructura Molecular , Unión Proteica , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/farmacocinética , Piridinas/síntesis química , Piridinas/farmacocinética , Piridonas/farmacocinética , Ratas , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
MicroRNA (miRNA) is small RNA of 20 to 22 nucleotides in length and is stably present in plasma. Regulating the expression of miRNA taken into cells has been suggested as a general therapeutic approach. We identified the novel anti-inflammatory miRNA hsa-miR-766-3p and investigated its biological function in human rheumatoid arthritis (RA) fibroblast-like synoviocyte MH7A cells. To verify the function of the miRNA present in the plasma of RA patients, we performed a comprehensive analysis of the miRNA expression during abatacept treatment and identified eight miRNAs with significantly altered expression levels. Among these eight miRNAs, miR-766-3p was found to have a clear function. The expression of inflammatory genes in response to inflammatory stimuli was suppressed in MH7A transduced with miR-766-3p. We showed that miR-766-3p indirectly reduced the activation of NF-κB and clarified that this mechanism was partially involved in the reduction of the mineralocorticoid receptor expression. In addition, the inflammatory responses were suppressed in other types of cells. These results indicate the novel function of miR-766-3p, findings that may aid in the development of therapies to suppress inflammation, not only in RA but also in other diseases.
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Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , MicroARNs/genética , Receptores de Mineralocorticoides/genética , Abatacept/administración & dosificación , Antiinflamatorios/administración & dosificación , Artritis Reumatoide/sangre , Artritis Reumatoide/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inflamación/sangre , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/patología , FN-kappa B/genética , Transducción de Señal/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Sinoviocitos/patologíaRESUMEN
OBJECTIVE: To estimate postoperative residual renal function after radical nephroureterectomy for upper tract urothelial carcinoma using the preoperative dynamic computed tomography renal cortex enhancement ratio in comparison with the split kidney glomerular filtration rate measured by 99m Tc-diethylenetriaminopentacetic acid renography. METHODS: A total of 47 patients who received radical nephroureterectomy and underwent both preoperative dynamic computed tomography and renography were the model-development cohort; and 109 patients who underwent dynamic computed tomography alone were the validation cohort. Postoperative renal function of the unremoved kidney was estimated using the following formulas: preoperative estimated glomerular filtration rate × the percentage of total renal cortex radiodensity for the intact kidney in Hounsfield units obtained from corticomedullary phase images in the computed tomography-based model, or the percentage of the total glomerular filtration rate measured by renography in the nuclear model. The correlation between observed and estimated postoperative renal function was determined. The computed tomography-based prediction model derived from linear regression analysis was validated externally. RESULTS: The correlation of computed tomography-based split renal function with the observed postoperative estimated glomerular filtration rate (r = 0.80) was equivalent to that of nuclear split renal function (r = 0.78). In the validation cohort, the computed tomography-based prediction model showed an equivalently strong correlation (r = 0.78). CONCLUSIONS: The present study showed that the percentage of total renal cortex radiodensity for the intact kidney is a useful tool for predicting unremoved kidney function in upper tract urothelial carcinoma patients, thereby allowing appropriate patient selection for perioperative cisplatin-based combination chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Transicionales/terapia , Corteza Renal/diagnóstico por imagen , Neoplasias Renales/terapia , Neoplasias Ureterales/terapia , Anciano , Carcinoma de Células Transicionales/diagnóstico por imagen , Carcinoma de Células Transicionales/patología , Quimioterapia Adyuvante/métodos , Femenino , Tasa de Filtración Glomerular , Humanos , Corteza Renal/fisiopatología , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/patología , Masculino , Modelos Biológicos , Nefroureterectomía/efectos adversos , Selección de Paciente , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Renografía por Radioisótopo/métodos , Estudios Retrospectivos , Pentetato de Tecnecio Tc 99m/administración & dosificación , Tomografía Computarizada por Rayos X , Neoplasias Ureterales/diagnóstico por imagen , Neoplasias Ureterales/patologíaRESUMEN
Dysregulation of histone H3 lysine 4 (H3K4) methylation has been implicated in the pathogenesis of several neurodevelopmental disorders. Targeting lysine-specific demethylase 1 (LSD1), an H3K4 demethylase, is therefore a promising approach to treat these disorders. However, LSD1 forms complexes with cofactors including growth factor independent 1B (GFI1B), a critical regulator of hematopoietic differentiation. Known tranylcypromine-based irreversible LSD1 inhibitors bind to coenzyme flavin adenine dinucleotide (FAD) and disrupt the LSD1-GFI1B complex, which is associated with hematotoxicity such as thrombocytopenia, representing a major hurdle in the development of LSD1 inhibitors as therapeutic agents. To discover LSD1 inhibitors with potent epigenetic modulation and lower risk of hematotoxicity, we screened small molecules that enhance H3K4 methylation by the inhibition of LSD1 enzyme activity in primary cultured rat neurons but have little impact on LSD1-GFI1B complex in human TF-1a erythroblasts. Here we report the discovery of a specific inhibitor of LSD1 enzyme activity, T-448 (3-((1S,2R)-2-(cyclobutylamino)cyclopropyl)-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzamide fumarate). T-448 has minimal impact on the LSD1-GFI1B complex and a superior hematological safety profile in mice via the generation of a compact formyl-FAD adduct. T-448 increased brain H3K4 methylation and partially restored learning function in mice with NMDA receptor hypofunction. T-448-type LSD1 inhibitors with improved safety profiles may provide unique therapeutic approaches for central nervous system disorders associated with epigenetic dysregulation.
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Benzamidas/farmacología , Histona Demetilasas/antagonistas & inhibidores , Aprendizaje por Laberinto/efectos de los fármacos , Trombocitopenia/inducido químicamente , Animales , Benzamidas/efectos adversos , Encéfalo/metabolismo , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Histona Demetilasas/metabolismo , Histonas/metabolismo , Humanos , Masculino , Metilación/efectos de los fármacos , Ratones , Neuronas/metabolismo , Cultivo Primario de Células , Proteínas Proto-Oncogénicas/metabolismo , Ratas , Proteínas Represoras/metabolismoRESUMEN
A 57-year-old Japanese man was admitted to the hospital with back pain and fever, multiple lung nodules, and abdominal aortic aneurysm (AAA). Laboratory tests performed at admission showed an increased proteinase 3 anti-neutrophil cytoplasmic antibody (PR3-ANCA) level. Video-associated thoracoscopic lung biopsy was performed; pathologic examination showed granulation tissue with necrosis and multinucleated giant cells. The diagnosis of granulomatosis with polyangiitis (GPA) was confirmed on the basis of the clinical presentation, laboratory findings, and lung biopsy. All symptoms were ameliorated, and the serum level of PR3-ANCA declined following treatment with prednisolone and cyclophosphamide. Although the association of GPA with AAA is rare, GPA may be included among the large vessel vasculitides that can give rise to aortic aneurysm.
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AIM: A challenge to the medical care of patients with rheumatoid arthritis (RA) is the management of the wide variety of information, including medication history and disease status, obtained from multiple sources to inform treatment decisions. To address this important clinical issue, we developed a data management system, based on smart device technology, and evaluated the benefit of this information to medical experts in helping them to form an impression of patients' health and disease, and treatment status before examination. METHODS: Fifty-seven patients with RA input relevant information about their condition and responses to a self-report health assessment questionnaire into a smart device template before their scheduled examination. The efficacy of the system was assessed as a decrease in examination time at each visit, and the correlation between the self-reported Multi-Dimensional Health Assessment Questionnaire and the 28-joint Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28-ESR), which was used as a gold standard. RESULTS: Examination duration was reduced in most patients at each visit. During the study, there were no limitations for patients with poor eyesight or severe arthropathy in using the system. In fact, the majority of patients found the smart technology to be easier to use than hand-written questionnaires and health forms, regardless of age and disease activity. CONCLUSIONS: Our findings support the use of smart technology to provide accurate patient-specific data and to streamline the process of medical care for patients with RA.
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Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Computadoras de Mano , Sistemas de Información en Salud , Autoinforme , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/psicología , Actitud del Personal de Salud , Femenino , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Examen FísicoRESUMEN
We retrospectively examined patients with ultrasonographically occlusive acute proximal deep vein thrombosis (DVT). All patients were categorized into two groups on the basis of whether great saphenous vein (GSV) flow toward the common femoral vein was detected (flow [+]; n=10) or undetected (flow [-]; n=10). We investigated the relationship between the GSV flow pattern and DVT recanalization. Thrombus recanalization, which is defined as diameter reduction to lower than 40% of the vessel diameter, was confirmed in seven of the flow (+), and none of the flow (-). This study proposes that the GSV flow pattern may be a simple marker for the recanalization of proximal occlusive DVT.
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BACKGROUND/AIM: We investigated the prognostic role of the albumin/globulin ratio (AGR) in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). PATIENTS AND METHODS: AGR was calculated as follows: AGR=serum albumin/(serum total protein-serum albumin). Associations of preoperative AGR with disease-free (DFS) and overall (OS) survival were assessed in 105 patients with UTUC undergoing RNU. RESULTS: Patients with preoperative AGR <1.24 and ≥1.24 were classified into the low (n=46, 44%) and high (n=59, 56%) groups, respectively. The 5-year DFS and OS were 77% and 78%, respectively. On multivariate analysis, high preoperative AGR was an independent predictor for both better DFS (hazard ratio(HR)=0.34, p=0.038) and OS (HR=0.24, p=0.006). The 5-year DFS and OS were significantly longer in the high-AGR group than in the low-AGR group (90% vs. 60%; 89% vs. 65%, both p<0.001). CONCLUSION: The AGR has prognostic value in patients with UTUC undergoing RNU.
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Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/cirugía , Globulinas/análisis , Nefroureterectomía , Albúmina Sérica/análisis , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/sangre , Carcinoma de Células Transicionales/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefroureterectomía/métodos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias Ureterales/sangre , Neoplasias Ureterales/diagnóstico , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/cirugía , Neoplasias Urológicas/sangre , Neoplasias Urológicas/mortalidadRESUMEN
BACKGROUND: Connective tissue growth factor (CTGF) is a multifunctional cellular protein and playing a role as a central mediator in tissue remodeling and fibrosis. The physiological function of CTGF in psoriasis is unknown. OBJECTIVE: The purpose of this study was to investigate the function of CTGF in psoriasis using the established imiquimod (IMQ)-induced psoriasis murine model and psoriasis patients. METHODS: Anti-CTGF monoclonal antibody was applied to IMQ induced psoriasis mice and those skin were clinically, pathologically and immunologically analyzed. Additionally, CTGF expression was analyzes using skin samples and plasma from psoriasis patients. RESULTS: CTGF expression was observed in the dermis from both IMQ-induced psoriatic mice and psoriasis patients. CTGF inhibition using an anti-CTGF antibody slightly worsened IMQ-induced dermatitis. In addition, the increase of CTGF showed tendency to suppress the psoriatic dermatitis through inhibition of suprabasal cells proliferation and macrophage infiltration in the skin. CTGF was also detected significantly higher in plasma from psoriasis patients comparing with healthy control. CONCLUSION: Our findings suggest that CTGF could contribute to the healing rather than the worsening of psoriasis skin lesions.
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BACKGROUND: MicroRNAs (miRNAs) are involved in the regulation of key biological processes and have been implicated in various diseases, including autoimmune disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is considered to be mediated by autoimmune reactions. To determine miRNA role in the development and progression of PM and DM, we performed plasma miRNA profiling in PM/DM patients before and after treatment. METHODS: Total RNA was isolated from plasma of 10 patients before and after treatment with prednisolone, or, in case of prednisolone resistance or complications, with the combination of calcineurin inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide. The expression of miRNAs was determined using miRNA microarray and validated by qRT-PCR. RESULTS: More differentially expressed miRNAs were found in plasma of DM patients compared to PM patients before and after treatment, and their profiles were different. Among the differentially expressed plasma miRNA identified by microarray, the levels of hsa-miR-4442 were confirmed by qRT-PCR to be significantly decreased by treatment. In addition, plasma hsa-miR-4442 content in active PM/DM significantly exceeded that in other active autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as in healthy individuals. The level of plasma hsa-miR-4442 was positively correlated with Skeletal Disease Activity in MITAX (Myositis Intention to Treat Activity Index). CONCLUSION: This is the first report describing plasma miRNA expression profiles in PM/DM patients. The present data suggest that plasma levels of miRNAs may be associated with polymyositis/dermatomyositis and hsa-miR-4442 could be used as a biomarker for PM/DM diagnosis and/or disease activity.