Delayed treatment with tumor necrosis factor inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs shows an excellent effect in patients with very early rheumatoid arthritis with poor prognosis factors

We aimed to investigate whether delayed treatment with tumor necrosis factor (TNF) inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs (DMARDs) was effective among patients with very early rheumatoid arthritis (RA) with poor prognosis factors. We examined 22 patients with very early RA who were positive for anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. The mean disease duration at entry was 14.1 weeks. A treat-to-target strategy, aiming at simplified disease activity index (SDAI) remission, was initiated with synthetic DMARDs. SDAI remission was not achieved in 9 of the 22 patients with synthetic DMARDs alone, and TNF inhibitors were added in these patients. SDAI values in these 9 patients were further examined for the following 6 months. The TNF inhibitors (infliximab 8, etanercept 1) were added at a mean interval of 34.1 weeks after the initiation of synthetic DMARDs. SDAI remission was achieved in 4 of the 9 patients (44.4%) at 3 months and in 8 of the 9 patients (88.9%) at 6 months after the introduction of the TNF inhibitors. Radiographic damage had not progressed in these patients. Delayed treatment with TNF inhibitors is effective and tolerable for patients with very early RA with poor prognosis factors.     

Serum level of oxidative stress marker is dramatically low in patients with rheumatoid arthritis treated with tocilizumab

Regarding the pathobiology of rheumatoid arthritis, oxidative stress induced by reactive oxygen species is an important mechanism that underlies destructive and proliferative synovitis. Abundant amounts of reactive oxygen species have been detected in the synovial fluid of inflamed rheumatoid joints. It is reported that drugs that block tumor necrosis factor-?? reduce the oxidative stress marker levels in patients with rheumatoid arthritis. In this study, we measured reactive oxygen species using a free radical analytical system in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, tumor necrosis factor-??-blocking drugs (infliximab, etanercept), and an interleukin-6-blocking drug (tocilizumab). The serum level of oxidative stress was drastically low in patients with rheumatoid arthritis treated with tocilizumab, suggesting that interleukin-6 blocking therapy reduces not only joint damage, but also vascular degeneration in patients with rheumatoid arthritis. We believe that such a drastic effect would reduce the incidence of cardiovascular events and mortality in patients with rheumatoid arthritis.     

Efficacy of the regimen using twice-daily β-interferon followed by the standard of care for chronic hepatitis C genotype 1b with high viral load

Aim: In patients with refractory genotype 1b chronic hepatitis C with high viral loads, we retrospectively compared the efficacy of standard of care treatment (SOC: combined PEG‐IFN‐α‐2b/ribavirin for 48 weeks) and a regimen in which 2 weeks of SOC induction was replaced by twice‐daily β‐interferon alone (IFN‐β induction therapy). Methods: Seventeen patients received the IFN‐β induction therapy plus SOC (IFN‐β induction group) and 13 patients received SOC alone (SOC group). Results: In the IFN‐β induction group and SOC group, early virological response (EVR) rates were 88.2% and 53.8%, respectively. The end of treatment rates were 100.0% and 92.3%, and sustained virological response (SVR) rates were 70.6% and 53.8%, respectively. By induction with IFN‐β, even in refractory cases, the high virus negative conversion rate in the early treatment phase and actions of pegylated IFN‐α‐2b and ribavirin in the maintenance treatment phase led to an additive effect. In the analysis of contributing factors, only the achievement of EVR was associated with a significant difference in SVR (P = 0.0011). The univariate logistic regression analysis showed that only IFN‐β treatment was associated with a significant difference in EVR (P = 0.0492, odds ratio = 6.248, 95% confidence interval = 1.026–40.252), whereas no significant factors were found in the multivariate analysis due to small samples. Conclusion: IFN‐β induction therapy with higher EVR might be beneficial for protease inhibitor‐refractory chronic hepatitis C patients.     

Eosinophil count is positively correlated with coronary artery calcification

Recent studies suggested that allergic disorders and increased eosinophil count were associated with atherosclerosis. The purpose of this study was to assess the relationship between eosinophil count and coronary artery calcification (CAC). We performed a cross-sectional study in 1363 consecutive participants with clinical suspicion of coronary heart disease (CHD). We evaluated the relationships between CAC score determined by multislice CT and peripheral eosinophil count as well as major cardiovascular risk factors, including age, body mass index, smoking status, hypertension, dyslipidemia, diabetes mellitus (DM), high-sensitivity C-reactive protein and estimated glomerular filtration rate (eGFR). Sex (P=0.0004), hypertension (P=0.0002), dyslipidemia (P=0.0004) and DM (P=0.0061) were associated with log(CAC+1), respectively. Positive correlations were found between log(CAC+1), and age (r=0.325, P<0.0001) and eosinophil count (r=0.165, P<0.0001). Negative correlations were found between log(CAC+1) and eGFR (r=-0.166, P<0.0001). Multivariate linear regression analysis demonstrated that age (β=0.314, P<0.0001), sex (β=0.124, P<0.0001), hypertension (β=0.084, P=0.0008), DM (β=0.108, P<0.0001), eGFR (β=-0.079, P=0.0021) and eosinophil count (β=0.147, P<0.0001) were independent determinants of log(CAC+1). In conclusion, eosinophil count correlated positively with CAC in participants with clinical suspicion of CHD.     

Electrocardiographic determinants of the polymorphic QRS morphology in idiopathic right ventricular outflow tract tachycardia

Coupling Intervals and Polymorphic QRS Morphologies . Introduction: Premature ventricular contractions (PVCs) arising from the right ventricular outflow tract (RVOT) can trigger polymorphic ventricular tachycardia (PVT) or ventricular fibrillation (VF) in patients with no structural heart disease. We aimed to clarify the ECG determinants of the polymorphic QRS morphology in idiopathic RVOT PVT/VF. Methods and Results: The ECG parameters were compared between 18 patients with idiopathic PVT/VF (PVT‐group) and 21 with monomorphic VT arising from the RVOT (MVT‐group). The coupling interval (CI) of the first VT beat was comparable between the 2 groups. However, the prematurity index (PI) of the first VT beat was smaller in the PVT‐group than in the MVT‐group (P < 0.001). Furthermore, the QT index, defined as the ratio of the CI to the QT interval of the preceding sinus complex, was also smaller for the PVT/VF in the PVT‐group than that for the VT in the MVT‐group (P < 0.01). In the PVT‐group, the CI of the first VT beat was comparable between that of VT and isolated PVCs, but the PI of the first VT beat was shorter for VT than isolated PVCs (P < 0.05). The PI was the only independent determinant of the polymorphic QRS morphology (odd ratio = 2.198; 95% confidence interval = 1.321–3.659; P = 0.002). Conclusion: The smaller PIs of the first VT beat may result in a polymorphic QRS morphology. (Cardiovasc Electrophysiol, Vol. 23, pp. 521‐526, May 2012)     

Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes

ObjectiveAdiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients.Research design and methodsWe enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9 ± 7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction).ResultsThe prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend = 0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p = 0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR) = 1.49 with 95%CI 1.09–2.05, p = 0.0125) and GG genotype (OR = 1.66 with 95%CI 1.13–2.43, p = 0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR = 1.67 with 95%CI 1.14–2.44, p = 0.0090) but not in the subjects with TT or GT genotype (OR = 1.17 with 95%CI 0.73–1.89, NS).ConclusionsIt is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.     

Endoscopic and clinical features of gastric ulcers in Japanese patients with or without Helicobacter pylori infection who were using NSAIDs or low-dose aspirin

Background

The endoscopic characteristics of gastric ulcers in patients who were using non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin (LDA) and were infected with Helicobacter pylori remain unclear. We elucidated the endoscopic characteristics of gastric ulcers that occurred in the presence or absence of H. pylori infection and were associated with the use of these drugs.

Methods

A total of 379 patients with active-stage gastric ulcer were divided into three groups: H. pylori-positive patients using neither NSAIDs nor LDA (control group, n?=?216), H. pylori-positive or -negative patients using NSAIDs (NSAIDs group, n?=?100), and H. pylori-positive or -negative patients using LDA (LDA group, n?=?63). The differences among these groups in endoscopic characteristics of the ulcers (site, multiplicity, and morphology) were determined. The influence of an antacid drug, i.e., a proton pump inhibitor (PPI) or a histamine H₂ receptor antagonist (H₂RA), was also investigated.

Results

The NSAIDs group, regardless of H. pylori infection status, had higher incidences of antral, multiple, and irregularly shaped ulcers. The LDA group had a higher incidence of antral ulcers in H. pylori-negative patients and, regardless of H. pylori infection status, a higher incidence of multiple ulcers. However, the incidence of irregularly shaped ulcers in the LDA group did not differ from that in the control group. Neither the concomitant use of an antacid nor the dosing period of NSAIDs affected the results.

Conclusions

Our study elucidated the morphological characteristics of gastric ulcers in persons taking NSAIDs or LDA in the presence and absence of H. pylori infection. Our results may be clinically useful for inferring the causes of ulcers from their morphological characteristics.     

Maximum carotid intima-media thickness improves the prediction ability of coronary artery stenosis in type 2 diabetic patients without history of coronary artery disease

ObjectiveCarotid intima-media thickness (CIMT), a marker of early atherosclerosis and vascular remodelling, is one of the independent predictors of coronary artery disease (CAD). However, it is unknown whether ultrasonic assessment of carotid atherosclerosis, including CIMT, improves the prediction ability for CAD over and above conventional coronary risk factors in the diabetic patients.MethodsUltrasonic scanning of the common carotid artery (CCA), the carotid bulb (Bul), and the internal carotid artery (ICA) was performed. The site with the greatest IMT, including plaque lesions, was sought along the arterial walls and max-IMT (the greatest IMT in the observation-possible areas of the CCA, Bul and ICA) was measured. The association of max-IMT with coronary artery stenosis assessed by coronary computed tomography angiography and the incremental effect of adding max-IMT to the conventional risk factors for predicting coronary artery stenosis were evaluated in 241 asymptomatic type 2 diabetic patients.ResultsMultiple logistic regression analyses showed that max-IMT was significantly associated with coronary artery stenosis even after adjustment for conventional risk factors. ROC curve analysis revealed that the AUC significantly increased after addition of max-IMT to conventional coronary risk factors [from 0.64 (95% CI; 0.57–0.71) to 0.74 (95% CI; 0.67–0.80), p = 0.020]. The addition of max-IMT to conventional coronary risk factors increased the AUC in obese patients (from 0.58 to 0.76, p = 0.012) but not in non-obese patients (from 0.68 to 0.72, NS).ConclusionsIn type 2 diabetic patients without apparent cardiovascular disease, the addition of max-IMT to conventional risk factors substantially improves the risk stratification for CAD.     

Pulmonary C-fibers elicit both apneusis and tachypnea in the rabbit.

The effects of phenylbiguanide (PBG) on phrenic nerve and pulmonary C-fibers were studied in anesthetized spontaneously breathing rabbits with unilateral vagotomy. Right atrial injections of PBG at low (10 micrograms/kg) and high (100 micrograms/kg) dose resulted in a shallow tachypnea and apneusis followed by tachypnea, respectively, and these effects were blocked by procaine treatment of the vagus nerve. Also, the injection of PBG (100 micrograms/kg) still evoked the rapid shallow breathing preceded by apneusis in carotid chemoreceptor-denervated animals. Vigorous stimulation of pulmonary C-fibers by PBG (100 micrograms/kg) coincided with apneusis and the response was followed by a more modest increase in activity associated with tachypnea. Administration of PBG (10 micrograms/kg) into the right atrium caused an increase in pulmonary C-fiber activity associated with tachypnea. However, a small dose of PBG injected into the aortic circulation had no effect on the C-fiber activity but did inhibit respiration. These results suggest that the stimulation of pulmonary C-fibers via PBG injection can produce both inspiratory apnea and tachypnea.