カンセン チリョウ ニ アタラシイ ジダイ ノ マクアケ : セイブツガクテキ セイザイ

Psoriasis is a chronic inflammatory skin disease, which is clinically characterized by scaly erythemas on the whole body. In the fully developed lesions of psoriasis, the histological features have demonstrated epidermal hyperproliferation with infiltration of T lymphocytes in the dermal papillae. Although pre-biological systemic therapies has targeted mainly proliferative keratinocytes and activated T cells, their effects were limited or these therapies could not be applied for patients with severe organ failures. Therefore, more effective agents are expected to improve quality of life （QOL） of patients with psoriasis. Recent studies have showed what kinds of cells, cell surface molecules, and cytokines should play a pivotal role in the pathogenesis of psoriasis. Biological therapies targeting these molecules have proved to be so effective for obstinate lesions of psoriasis. Here, we describe clinical features and pathogenesis of psoriasis, and the characteristics of several conventional and biological therapies for psoriasis in Japan

The involvement of fibroblast growth factor receptor signaling pathways in dermatofibroma and dermatofibrosarcoma protuberans

Fibroblast growth factors (FGFs) and their receptors (FGFRs) control a wide range of biological functions ; however, their involvement in the pathogenesis of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is currently unknown. In this study, we first confirmed the histological diagnosis by detecting fusion COL1A1-PDGFB transcripts in DFSP, and examined the expression of all FGFRs (FGFR1-4), some of their ligands (FGF1, 2, 9), and forkhead box N1 (FOXN1) as a downstream target of FGFR3 in DF and DFSP by immunohistochemical analysis. Although we failed to detect the expression of FGF1 and FGF9 as specific ligands for FGFR3 in DF, overexpression of FGFR3 and FOXN1 was observed in the epidermal regions of DF, suggesting that the epidermal regions of DF were similar to seborrhoeic keratosis both in terms of histological features and the activation of FGFR3/FOXN1. In addition, strong expression of FGF2 and FGFR4 was observed in the tumor lesions of DF. Expression patterns of FGFR3/FOXN1 and FGF2/FGFR4 in DF were in contrast with those of DFSP. The activation of FGFR signaling pathways may be not only relevant to the pathogenesis of DF, but also very useful in the differential diagnosis of DF and DFSP

Impact of renal insufficiency on long-term clinical outcome in patients with heart failure treated by cardiac resynchronization therapy

AbstractBackgroundRenal insufficiency is recognized as a predictor of mortality and adverse outcome in heart failure (HF) patients. However, the long-term clinical outcome of cardiac resynchronization therapy (CRT) in Japanese HF patients with renal insufficiency remains uncertain.MethodsWe evaluated 67 consecutive patients who underwent CRT at our hospital. The patients were divided into two groups according to a baseline estimated glomerular filtration rate (e-GFR) cut-off value of 50ml/min, which is defined as the time at which patients should be referred to a nephrologist, by the Japanese Society of Nephrology. Follow-up echocardiographic findings and renal function were examined at 3–6 months after CRT. Then, we compared long-term clinical outcomes between the two groups, and analyzed the effect of CRT on renal function, echocardiographic parameters and cardiac survival.ResultsDuring a mean follow-up period of 30.3 months, patients with advanced renal insufficiency (e-GFR<50ml/min) had significant higher all-cause mortality (log-rank p=0.033) and higher cardiac mortality combined with HF hospitalization (log-rank p=0.017) than patients with e-GFR≥50ml/min. Multivariate analysis revealed that advanced renal insufficiency was an independent predictor of cardiac mortality combined with HF hospitalization (odds ratio=3.01, p=0.008). Subgroup analysis in the baseline advanced renal insufficiency group revealed that patients with preserved renal function by CRT (<10% reduction in e-GFR) had a higher rate of decrease of left ventricular end-systolic diameter (−14.0% vs. −0.8%, p=0.023) and lower cardiac mortality combined with HF hospitalization (log-rank p=0.029) compared with patients with deterioration of renal function (≥10% reduction in e-GFR).ConclusionsThe present study suggests that advanced renal insufficiency is quite useful for the prediction of worsening clinical outcomes in HF patients treated by CRT. Preservation of renal function by CRT brings about better cardiac survival through prevention of adverse cardiac events, even in HF patients with advanced renal insufficiency

Análisis de las comorbilidades en pacientes con colitis ulcerosa: una herramienta para prevenir las exacerbaciones en casos de colitis ulcerosa

There have been previous studies, especially in Western countries and even in some areas in Asia, about extra-intestinal manifestations (EIMs) and its link with the outcome of inflammatory bowel disease (IBD), which includes Crohn’s disease (CD), and ulcerative colitis (UC). This link is crucial when discussing a patient’s prognosis and important when dealing with UC management. The aim of this study was to clarify the most common comorbidities associated with UC, emphasizing immunologic comorbidities in Japan. This study was a retrospective analysis performed at Nagoya University Hospital. The data collection started in March, 2019, and continued for two years. We retrieved the medical records of 105 patients with UC diagnosis, from which the data of 176 EIMs were extracted and analyzed. Results showed that EIMs with UC in the active phase accounted for 43.7% of total EIMs. Twenty-six patients with immune-mediated inflammatory disease frequently had an active phase (odds ratio [OR] 3.84, 99% CI, 1.44–10.27). Comorbidities showing an active manifestation of symptoms and UC in the active phase were significantly correlated in patients with immunological comorbidities, such as peripheral arthritis (r = 0.97, p < 0.01) and rheumatoid arthritis (RA) (r = 0.99, p < 0.01), as well as in patients with primary sclerosis cholangitis (PSC) (r = 0.98, p < 0.01). In conclusion, this analysis suggests the importance of having full comprehension of how immunological comorbidities affect the natural development of UC, which is of vital importance to prevent further UC complications and properly adjust the management of the disease.Se trata de un análisis retrospectivo que estudia múltiples comorbilidades de índole inmunológico que se da en pacientes con colitis ulcerosa. Este estudio se llevó a cabo en el hospital universitario de la Universidad de Nagoya. Se recolectó datos de 105 pacientes con colitis ulcerosa, de los cuales 176 comorbilidades extraintestinales fueron analizadas. Se encontró que comorbilidades con manifestación activa de síntomas y con colitis ulcerosa en fase activa fueron significativamente correlacionadas en pacientes con comorbilidades inmunológicas, tales como artritis periféricas (r=O.97, P<O.OI ), artritis reumatoide (r=O.99, P<O.OI ), así como pacientes con colangitis esclerosa primaria (r=O.98, P<O.OI ). En conclusión, este análisis sugiere la importancia de tener plena comprensión de cómo las comorbilidades inmunológicas afectan el desarrollo natural de la colitis ulcerosa, lo cual es de vital importancia para prevenir mayores complicaciones de la colitis ulcerosa y ajustar adecuadamente el manejo de la enfermedad.Japón. Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología (Monbukagakusho)Artículo de investigació

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=−0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=−0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=−0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function