Age at the time of hip fracture in patients with rheumatoid arthritis is 4 years greater than it was 10 years before, but is still younger than that of the general population.

Objective: To investigate the characteristics of hip fractures in patients with rheumatoid arthritis (RA).Methods: Between 2012 and 2015, 789 hip fractures were treated at our hospital. Patients with RA were checked and their characteristics were compared with data recorded 10 years before, and with the general population.Results: There were 11 patients with RA, who were all female, and the mean age was 76 ± 7.0 years. The age at the time of hip fracture was 4 years older than that recorded 10 years before (72 ± 4.5 years, p < .05), but was younger than that of the general population (84 ± 8.0 years, p < .001). The mean prednisolone dose of 2.5 ± 2.6 mg/day was lower than that recorded 10 years before (4.8 ± 2.9 mg/day, p < .05). The rate of patients treated with anti-osteoporotic medications at fracture (73%) was higher than 10 years before (42%); however, the difference was not significant. The incidence of secondary fracture was not high compared to the general population. No mortality was recorded at 1 year, and no infective complications occurred.Conclusion: The age at the time of hip fracture in RA patients is increasing, but is still younger than that of the general population.

IL-6-positive classical Hodgkin's lymphoma co-occurring with plasma cell type of Castleman's disease: report of a case.

We present a case of classical Hodgkin's lymphoma (HL) co-occurring with histological features of Castleman's disease (CD). A 25-year-old man presented with left supraclavicular and axillary lymph node swelling and mediastinal mass. Using an initial biopsy specimen from left axillary lymph node, a tentative diagnosis of multicentric CD of plasma cell type was made. The serum level of interleukin-6 (IL-6) was elevated. The patient was treated with immunosuppressive therapy containing tocilizumab (TCZ). Shrinkage of mediastinal mass and axillary lymph nodes was seen; however, swelling of his left axillary lymph nodes reemerged, even after therapy with TCZ. A second left axillary lymph node biopsy was performed and a diagnosis of nodular sclerosis of classical HL without histologic features of CD was made. The initial biopsy specimen was re-examined, and scattered CD30+ Hodgkin/Reed-Sternberg cells were found in the interfollicular area. Interestingly, Hodgkin/Reed-Sternberg cells and surrounding reactive cells in both lymph nodes were stained with anti-IL-6 antibody. We emphasize that biopsy specimens with HL involvement may also have histologic features reminiscent of those seen in CD. To our knowledge, this is the first report to provide a detailed description of this pathology, including a survey of IL-6 and clinical course upon treatment with TCZ.

IgG4-related chronic tubulointerstitial nephritis without autoimmune pancreatitis and the time course of renal function.

We report an elderly man with chronic tubulointerstitial nephritis (TIN) showing a high serum immunoglobulin G4 (IgG4) concentration. His serum creatinine (Scr) level had gradually increased from 0.9 mg/dL to 5.6 mg/dL over 18 months. Renal biopsy showed marked IgG4-positive plasma cell infiltration in the interstitium without glomerular abnormalities and IgG4-related TIN was diagnosed. Oral prednisolone reduced his Scr and IgG4 levels immediately. The present case indicates that IgG4-related TIN can not only progress rapidly but also chronically over a long period without significant urinary abnormalities, and we should consider hidden IgG4-related TIN in cases of chronic renal insufficiency.

HELLP syndrome, multiple liver infarctions, and intrauterine fetal death in a patient with systemic lupus erythematosus and antiphospholipid syndrome.

We report a case of HELLP syndrome, multiple liver infarctions, and intrauterine fetal death in a woman in the 17th week of pregnancy with SLE and APS who had been in remission on a regimen of low-dose prednisolone and aspirin. An increase in the dosage of corticosteroid together with intravenous heparin infusion led to improvement of the clinical symptoms, laboratory parameters, and multifocal low-density liver lesions detected by computed tomography. Early onset and signs of severe organ involvement are the characteristic features of HELLP syndrome associated with APS, and patients that are at risk should be followed up carefully.

Mortality predictors after 10 years of dialysis: a prospective study of Japanese hemodialysis patients.

BACKGROUND: This work aimed to examine the predictive value for death of various clinical variables after long-term hemodialysis (HD). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A total of 947 patients (597 men and 350 women, aged 21 to 93 yr) who were undergoing maintenance HD in Niigata, Japan, were stratified into two cohorts: Those with >10 yr of prior HD at study enrollment (n = 391) and those with < or =10 yr of previous therapy (n = 556). The survival of patients was examined for up to 40 mo (1999 to 2003) with the Cox proportional hazards model. Baseline clinical and dialysis data and serum biochemistries were used as independent variables. For adjustment for bias in patient selection, patient survival in either cohort was analyzed separately. RESULTS: In patients with >10 yr of HD, high pulse pressure, cerebrovascular disease, low serum creatinine, and low Kt/V values were the mortality risk predictors, whereas for those with < or =10 yr of HD, age and cerebrovascular disease were independent risk predictors for death. Diabetes, coronary artery disease, serum albumin, and C-reactive protein were NS predictors in those with long-term HD. CONCLUSIONS: Providing adequate dosage of dialysis and achieving a better control of pulse pressure may further improve survival in selected patients who had undergone HD for >10 yr.

SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis.

To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis.

Bezafibrate suppresses rat antiglomerular basement membrane crescentic glomerulonephritis.

BACKGROUND: The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARalpha on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model. METHODS: The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells. RESULTS: Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats. CONCLUSION: BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis.

Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.

BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet. METHODS: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene. RESULTS: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype. CONCLUSIONS: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

Interaction between ACE and ADD1 gene polymorphisms in the progression of IgA nephropathy in Japanese patients.

An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and alpha-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; chi2=6.062, P=0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P=0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P=0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.