The diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve. Comparison with myocardium perfusion imaging.

To compare the diagnostic performance of on-site workstation-based computed tomography-derived fractional flow reserve (CT-FFR)Few data of CT-FFR were reported regarding the diagnostic performance for detecting hemodynamically significant coronary artery disease (CAD). This retrospective single-center analysis included 132 vessels in 77 patients who underwent CT angiography, myocardial perfusion imaging (MPI), and invasive FFR. The correlation coefficient between CT-FFR and invasive FFR and optimal cut-off value for CT-FFR to identify invasive FFR ≤ 0.8 were evaluated. The diagnostic accuracies of CT- FFR, and MPI were evaluated using an area under the receiver-operating characteristic curve (AUC) with invasive FFR as a reference standard. Diagnostic performance of CT-FFR was also evaluated concerning lesion characteristics, including intermediate lesions, left main lesions, tandem lesions, and/or diffuse lesions, and coronary calcium (Agatston score over 400). The Receiver Operating Characteristic curve analysis showed that the optimal cut-off value of CT-FFR for detecting invasive FFR ≤ 0.80 was 0.80 [AUC = 0.83, 95%CI: 0.76-0.90). Diagnostic sensitivity, specificity, positive and negative predictive value, and accuracy of CT-FFR when compared with those of MPI regarding per-patient analysis were 93% vs. 63%, 48% vs. 61%, 81% vs. 79%, 73% vs. 41%, and 79% vs. 62%, respectively, and for per-vessel analysis were 89% vs. 24%, 66% vs. 82%, 75% vs. 61%, 83% vs. 48%, and 78% vs. 51%, respectively. The AUC of the CT-FFR was significantly higher than MPI (0.83 vs. 0.57, p < 0.0001) regarding the per-vessel analysis. No differences in the diagnostic performance of CT-FFR were noted in the presence of intermediate lesions, left main lesions, tandem lesions, and/or diffuse lesions, and severe coronary calcium. On-site CT-FFR delivered a higher diagnostic performance than MPI for detecting CAD with invasive FFR ≤ 0.8, indicating the potential of CT-FFR as the gatekeeper of invasive coronary angiogram as well as percutaneous coronary intervention.

Correction to: Decline in the estimated glomerular filtration rate (eGFR) following metabolic control and its relationship with baseline eGFR in type 2 diabetes with microalbuminuria or macroalbuminuria.

[This corrects the article DOI: 10.1007/s13340-021-00517-2.].

Decline in the estimated glomerular filtration rate (eGFR) following metabolic control and its relationship with baseline eGFR in type 2 diabetes with microalbuminuria or macroalbuminuria.

AIMS: Relationship between baseline eGFR and the rate of decline in eGFR was investigated in diabetic kidney disease. MATERIALS AND METHODS: Patients with type 2 diabetes with microalbuminuria (MI) (n = 124) or macroalbuminuria (MA) (n = 81) received team-based medical care to prevent the development of diabetic kidney disease. The decline in eGFR over 4 years, divided into the first year and subsequent 3 years, was estimated by linear-mixed modeling. RESULTS: The eGFR showed a rapid decline during the first year, followed by a slower decline. On multiple regression analysis, the baseline eGFR was positively correlated with HbA1c in MI and negatively correlated with carotid plaque in MI and in MA. Subsequent eGFR decline following 1-year intervention was negatively correlated with the baseline eGFR and HbA1c level at 1 year in MI, whereas it was positively correlated with baseline eGFR and negatively correlated with the amount of proteinuria at 1 year in MA. Even in maintained baseline eGFR(≧ 60 ml/min/1.73 m2) at the first year, when HbA1c ≧ 7.5%, eGFR reduction rate and years to ESKD were much faster and shorter, compared to the group of HbA1c < 7.5% [- 3.44 (SE 1.137) vs. - 1.695 (SE 0.431) ml/min/1.73 m2/year, and 19.4 vs. 35.7 years, respectively]. In MA, lower eGFR (< 60 ml/min/1.73 m2) and higher proteinuria (≧ 2.25 g/gCre) had a much faster eGFR decline and shorter time to ESKD, compared to the group of maintained eGFR and lower proteinuria (< 2.25 g/gCre) [- 5.240 (SE 1.537) vs. - 2.67 (SE 0.997) ml/min/1.73 m2/year, and 4.41 vs. 22.8 years, respectively]. CONCLUSIONS: In MI, even in maintained eGFR, the continued increase in eGFR in response to hyperglycemia (HbA1c ≧ 7.5%) led to a faster decline in renal function and in MA, lower eGFR, with an increase in proteinuria, contributed to rapid decline of renal function. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13340-021-00517-2.

Relation of Serum Lipoprotein(a) Levels to Lipoprotein and Apolipoprotein Profiles and Atherosclerotic Diseases in Japanese Patients with Heterozygous Familial Hypercholesterolemia: Familial Hypercholesterolemia Expert Forum (FAME) Study.

AIMS: Lipoprotein(a) [Lp(a)] is a plasma lipoprotein consisting of a low-density lipoprotein (LDL)-like particle with apolipoprotein (Apo)(a), attached via a disulfide bond to Apo B100. Previous studies have shown that high Lp(a) levels are associated with an increased risk of cardiovascular disease in patients with familial hypercholesterolemia (FH). To date, limited data are available as to distribution of Lp(a) in FH and associations of Lp(a) with other lipid profiles and cardiovascular disease. Our study aimed to investigate serum Lp(a) levels in relation to other lipid profiles and clinical conditions in the national largest-ever cohort of Japanese FH patients. METHODS: This study is a secondary analysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study that includes a Japanese nationwide cohort of FH patients. In 399 patients under treatment for heterozygous FH who had a baseline measurement of serum Lp(a), the present study examined the distribution of Lp(a) levels and associations of Lp(a) with other lipid profiles and clinical conditions including coronary artery disease (CAD). RESULTS: The distribution of Lp(a) was skewed to the right with a median of 20.8 mg/dL, showing a log-normal distribution. Serum Apo B and Apo E levels were positively associated with Lp(a) levels. Age-adjusted mean of Apo B was 8.77 mg/dL higher and that of Apo E was 0.39 mg/dL higher in the highest category (40+ mg/dL) of Lp(a) than in the lowest category (＜20 mg/dL). LDL-C levels did not show such an association with Lp(a) levels. A tendency towards a positive relationship between Lp(a) and prevalent CAD was observed in men. CONCLUSION: Our study demonstrated a distribution pattern of Lp(a) in Japanese FH patients and positive relationships of Lp(a) with Apo B and Apo E levels.

Development of type 1 diabetes in a patient treated with anti-interleukin-6 receptor antibody for rheumatoid arthritis.

Interleukin-6 is a pleiotropic cytokine that plays a pathogenic role in type 1 diabetes. Therefore, anti-interleukin-6 receptor antibody, tocilizumab, used for the treatment of rheumatoid arthritis, is considered a candidate for immune intervention in type 1 diabetes. Here, we report the case of a 73-year-old woman (HLA-DR9-DQ3 homozygote) with well-controlled rheumatoid arthritis who developed type 1 diabetes while receiving tocilizumab treatment. At 57 years-of-age, the patient was diagnosed with rheumatoid arthritis, for which she underwent tocilizumab therapy that enabled complete suppression of her joint inflammation. A total of 17 months after starting tocilizumab therapy, she noticed polydipsia, polyuria, general fatigue and weight reduction (-2 kg/month), and was diagnosed with type 1 diabetes with diabetic ketoacidosis based on an arterial pH of 7.26, serum ketone body of 7,437 µmol/L, blood glucose level of 925 mg/dL, glycated hemoglobin of 13.2% and the presence of anti-islet autoantibodies. This case report shows valuable insight regarding the effect of anti-interleukin-6 receptor antibody therapy on type 1 diabetes prevention.

Factors Associated with Carotid Atherosclerosis and Achilles Tendon Thickness in Japanese Patients with Familial Hypercholesterolemia: A Subanalysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study.

AIMS: Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol levels, xanthomas including Achilles tendon thickening, and premature coronary artery disease (CAD). Carotid intima-media thickness (IMT) is a well-established surrogate marker for CAD in FH and Achilles tendon thickening is a specific physical finding in patients with FH. The objective of the present study was to identify factors associated with carotid IMT and Achilles tendon thickness in FH heterozygotes on lipid-lowering therapy. This study also aimed to examine the follow-up changes in carotid IMT and Achilles tendon thickness among them in the current real-world FH practice. METHODS: The current study is a subanalysis of the Familial Hypercholesterolemia Expert Forum (FAME) Study. The severity of carotid atherosclerosis was assessed with the maximal and mean IMT using ultrasonography, and Achilles tendon thickness was measured using X-rays. The present study used 571 patients under medical treatment for heterozygous FH who had baseline measurements for maximal IMT (n=511), mean IMT (n=459), or Achilles tendon thickness (n=486). The IMT was measured annually, and Achilles tendon thickness was evaluated every two years. RESULTS: Higher LDL cholesterol (LDL-C) level and lower HDL cholesterol (HDL-C) level were associated with greater maximal and mean IMT as well as greater Achilles tendon thickness. Achilles tendon thickness tended to be greater in patients who had a smoking history than in never-smokers. Maximal IMT and Achilles tendon thickness were significantly greater in patients with CAD than in those without. Additionally, lower HDL-C level and hypertension were associated with higher values of maximal and mean IMT, suggesting the importance of comprehensive risk management including reduced HDL-C and blood pressure control in FH care. In longitudinal observations, percentage changes in maximal IMT and mean IMT gradually increased during the observation period. In contrast, percentage changes in Achilles tendon thickness became progressively thinner throughout the observation period. CONCLUSIONS: We found a positive association between LDL-C levels and severity of carotid atherosclerosis in heterozygous FH patients on treatment. This observation suggests the insufficiency of lipid-lowering therapy and the presence of therapeutic inertia among clinicians in the real-world FH practice.

Effectiveness and Safety of Lipid-Lowering Drug Treatments in Japanese Patients with Familial Hypercholesterolemia: Familial Hypercholesterolemia Expert Forum (FAME) Study.

AIMS: Familial hypercholesterolemia (FH) is a genetic disorder characterized by high serum levels of low-density lipoprotein (LDL)-cholesterol (LDL-C), tendon and skin xanthomas, and premature coronary artery disease (CAD). In Japan, detailed information on the current status of drug therapies for patients with FH has not been reported so far, and their efficacy and safety have not been clarified. After the introduction of ezetimibe, which can further reduce serum LDL-C levels on top of statins, the changes of management for FH patients with these drugs are of particular interest. The current study aimed to evaluate the clinical status of FH heterozygotes and homozygotes, especially focusing on the real-world lipid-lowering drug therapy, attained serum LDL-C levels, and cardiovascular events at registration and during the follow-up. METHODS: The FAME Study enrolled 762 heterozygous (including 17 newly diagnosed cases) and 7 homozygous FH patients from hospitals and clinics nationwide. Diagnosis of FH was based upon the criteria defined in the Study Report in 2008 of the Research Committee on Primary Hyperlipidemia supported by Grants-in-Aid for Scientific Research from the Japanese Ministry of Health, Labor and Welfare. Data analysis was primarily carried on heterozygous FH patients. RESULTS: Xanthoma or thickening of the Achilles tendon was observed in more than 80% of the patients. CAD was recorded in 23% of patients. Patients with parental and sibling CAD accounted for 47% and 24%, respectively. At baseline, patients without CAD who had LDL-C ＜100 mg/dL accounted for 12.3% and those with CAD who had attained the target (LDL-C ＜70 mg/dL) in the secondary prevention accounted for only 1.8%. In the multiple logistic analysis, male sex, age ＞40, heterozygous FH score ＞20, hypertension, and sibling CAD were significantly and positively associated with prevalent CAD, whereas serum HDL-cholesterol levels showed a significant inverse association with CAD. Patients treated with statin alone, statin＋ezetimibe, statin＋resin, or statin＋probucol accounted for 31.1%, 26.3%, 4.0%, and 3.7%, respectively. Patients treated with three-drug combination (statin＋ezetimibe＋resin or statin＋ezetimibe＋probucol) accounted for 7.5%. Statins and ezetimibe were used in 88.0% and 48.0% at the baseline, respectively. Although high-intensity statins were mainly prescribed, statin doses were much lower than those reported in Western countries. The addition of ezetimibe resulted in ~20% reduction in serum LDL-C. CAD was diagnosed in 17 patients with 21 episodes during follow-up. The Cox hazard model analysis demonstrated that male sex, CAD at the baseline, and parental CAD were related to the development of atherosclerotic cardiovascular disease (ASCVD) events. Furthermore, an increase in serum HDL-C was associated with a significant reduction of ASCVD events, while serum LDL-C and triglyceride levels were not related to ASCVD events. CONCLUSION: The prevalence of CAD in Japanese patients with heterozygous FH is still very high. In most of the cases, the target level of serum LDL-C was not achieved for primary and secondary prevention of CAD, suggesting that a more aggressive LDL-C lowering and appropriate management of residual risks are necessary.

Late catch-up phenomenon associated with stent fracture after sirolimus-eluting stent implantation: incidence and outcome.

OBJECTIVE: To examine the long-term outcome of the stent fracture (SF) and the potential predictive factors contributing to in-stent restenosis (ISR) in the fractured stent. BACKGROUND: The SF is thought to be a higher risk of ISR in drug-eluting stent, although SF does not always develop ISR. METHODS: The consecutive 1,228 de novo lesions in 1,079 patients who underwent sirolimus-eluting stents implantation and assessed by 8 months follow-up coronary angiography were retrospectively analyzed. RESULTS: One hundred and seventeen SFs (9.5%) were identified in 100 patients and 22 (18.8%) SFs revealed ISR at the first follow-up. In addition, 16 (13.7%) developed new ISRs from 95 residual SFs without ISR prior to the second follow-up. Overall, 38 (32.5%) of all 117 SFs developed ISR, and 16 (42.1%) of 38 SFs occurred in a late phase beyond the first 8 months follow-up. A higher risk of ISR in the SF site was associated with the chronic total occlusion (ISR vs. no ISR: 34.2% vs. 16.5%, P = 0.0304), calcified lesions (55.3% vs. 34.2%, P = 0.0299), and correspondence 89.5% versus 43.0%, P < 0.0001 (SF site occurring at the original target lesion site) in the univariate analysis. The correspondence was identified as the only strong predictive factor for ISR at the SF site according to a multivariate logistic regression analysis (odds ratio 12.6, 95% confidence interval 3.82-53.5, P < 0.0001). CONCLUSIONS: SF occurring at the site of the original target lesion was a strong independent predictor of ISR. This indicates the need for a careful, long-term follow-up in those situations, even when no significant ISR is initially detected.

Prediction of acute coronary syndrome by using multislice computed tomography. -Can we predict the onset of acute coronary syndrome? (Pro)-.

Predicting the occurrence of acute coronary syndrome (ACS) is a major clinical challenge for cardiologists. Multi-slice computed tomography (CT) has enabled easy detection and assessment of atherosclerotic coronary plaque, and therefore has considerable potential in the prevention of ACS. The recent development of 64-slice cardiac CT enables detailed information on both plaque properties and characteristics to be obtained with excellent diagnostic accuracy. Cardiac CT therefore has great potential for detecting the unstable plaques that are prone to result in ACS.

Efficacy of omarigliptin, once-weekly dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes.

BACKGROUND: Omarigliptin is one of several once-weekly dipeptidyl peptidase-4 inhibitors (DPP-4is). Despite the high frequency of switching from various daily DPP-4is to omarigliptin in actual clinical practice, data regarding its efficacy in patients with type 2 diabetes (T2D) after switching are limited. AIM: To analyze the efficacy of omarigliptin in Japanese patients with T2D who had previously received treatment with other glucose-lowering agents. METHODS: Forty-nine T2D patients treated for the first time with omarigliptin were recruited retrospectively and divided into four groups defined as either add-on or switched from daily DPP-4is: switched from linagliptin, switched from sitagliptin, and switched from vildagliptin. During a 3-mo follow-up, the clinical parameters among these groups were assessed and compared, with the impact of the switch on glycemic variability as measured by continuous glucose monitoring also being evaluated in the switched groups. RESULTS: Hemoglobin A1c levels saw a significant decrease of -0.32% ± 0.41% in the add-on group (P = 0.002). However, the other groups' variables depended on the pre-switch daily DPP-4i: switched from linagliptin, -0.05% ± 0.22%; switched from sitagliptin, -0.17% ± 0.33%; and switched from vildagliptin, 0.45% ± 0.42%, which saw significant worsening (P = 0.0007). Multivariate logistic regression analysis revealed that switching from vildagliptin to omarigliptin was independently associated with worsening glycemic control (P = 0.0013). The mean and standard deviation of sensor glucose value, the mean amplitude of glycemic excursions, and the mean of daily difference significantly improved when switching the patient from either linagliptin or sitagliptin to omarigliptin. However, in patients switched from vildagliptin, not only did the glucose variability indices see no improvements, the mean of daily difference even underwent significant worsening. CONCLUSION: Administering omarigliptin as add-on therapy or switching to it from sitagliptin and linagliptin, but not vildagliptin, improves glycemic control and thus should help in decision making when selecting DPP-4is for T2D patients.

Comparison of Diagnostic Performance of Fractional Flow Reserve Derived from Coronary Computed Tomographic Angiography Versus Single-Photon Emission Computed Tomographic Myocardial Perfusion Imaging.

Fraction flow reserve (FFR) derived from computed tomography (FFRCT) has been proposed to be an effective gatekeeper for invasive angiographic referral. The purpose of the present study is to examine the real-world diagnostic performance of FFRCT and myocardial perfusion imaging as well as to assess the utility of FFRCT as a gatekeeper for invasive coronary angiography in patients suspected of having obstructive coronary artery disease. Total of 146 consecutive patients underwent both single-photon emission computed tomography (SPECT) and invasive FFR were evaluated. An FFRCT value 1 to 2 cm distal to a stenosis ≤0.80 was defined as positive for ischemia and a summed stress score ≥2 or transient ischemic dilatation ≥1.2 were positive for ischemia with the invasive FFR value of <0.80 serving as the gold standard. The patient-based sensitivity of FFRCT was significantly higher than SPECT (91 vs 52%, p <0.001) and exhibited similar positive predictive value (82 vs 82%, p = 0.91). These trends were observed even in patients with multivessel and left main trunk disease and those with severe coronary calcification. In conclusion, our data suggest that FFRCT has higher diagnostic performance characteristics than SPECT and details the superior FFRCT analysis in detecting patients with hemodynamically significant coronary artery disease. Our results support the clinical utility of FFRCT analysis as a gatekeeper for invasive coronary angiography in clinical practice.

Statin-induced autoimmune hepatitis in patients with type 1 diabetes: A report of two cases and literature review.

Statins are widely used medications for the treatment of hypercholesterolemia, as well as prevention of cardiovascular disease. We report two patients with type 1 diabetes who developed autoimmune hepatitis after the administration of statin. The first patient developed the marked elevation of liver enzymes 6 months into atorvastatin therapy. The second patient developed liver dysfunction 8 months after the initiation of rosuvastatin therapy. Liver biopsies in both patients showed either portal, interface and lobular hepatitis or a piece-meal necrosis with lymphocytes and plasma cell infiltration that were compatible with autoimmune hepatitis. Then, both patients were started on prednisolone, to which they responded well. Liver biopsy is to be considered for type 1 diabetes patients if there is no improvement of liver dysfunction after discontinuation of statins.

Characterization of patients with diabetes who were incidentally found to be glutamic acid decarboxylase autoantibody-positive by bridging-type enzyme-linked immunosorbent assay.

This study aimed to characterize diabetic patients incidentally found to be positive for glutamic acid decarboxylase autoantibodies (GADA) in general practice. Using bridging-type enzyme-linked immunosorbent assay, we screened 1,040 patients with phenotypic type 2 diabetes for GADA, finding 25 (2.4%) to be positive. However, on retesting, with a median interval of 19 days, 44% of GADA-positive patients turned negative (Disappearing Group). The mean age at diabetes onset was significantly higher (P < 0.05) and GADA titers at first determination were significantly lower (P < 0.001) in the Disappearing Group compared with the Persistent Positive Group. On initial screening, all patients in the Disappearing Group had GADA titers of <6.5 U/mL. The current study showed that a portion of phenotypic type 2 diabetic patients incidentally identified as GADA-positive were falsely positive, and that to avoid the misclassification, remeasurement of GADA is essential in cases showing very low titers.

The bifurcation study using 64 multislice computed tomography.

BACKGROUND: Various two-stent techniques have been applied to aggressively treat bifurcation lesions as the introduction of drug-eluting stents (DES) and the importance of the bifurcation angle and three-dimensional (3D) structure has come to be recognized. Recent 64 multislice computed tomography (MSCT) technology provides accurate information about the 3D bifurcation geometry of the coronary arteries and with reproducibility. OBJECTIVES: The purpose of this study is to disclose the coronary bifurcation angle and 3D structure in humans and elucidate the importance of bifurcation angle for the crush technique using MSCT. METHODS: Two hundred and nine patients who were suspected to have angina pectoris and underwent CT angiography using MSCT were examined. The 3D-volume rendering (VR) image was reconstructed by two technicians and was used for the assessment of each coronary bifurcation angles. RESULTS: The average LMT bifurcation angles (angle LMT-LAD, angle LMT-LCx, angle LAD-LCx) were 143 +/- 13 degrees , 121 +/- 21 degrees , and 72 +/- 22 degrees , respectively, the average angle LAD-D was 138 +/- 19 degrees , the average angle LCx-OM was 134 +/- 23 degrees , the average distal RCA bifurcation angles (angle RCA-4AV, angle RCA-4PD, angle 4AV-4PD) were 152 +/- 15 degrees , 137 +/- 20 degrees , and 61 +/- 21 degrees , respectively. In addition, a percentage of steep angled bifurcation (<110 degrees ) was significantly higher in the LMT (26%) than in other bifurcations (P < 0.05). CONCLUSIONS: LMT bifurcation has been shown to have a higher rate of steep angled bifurcation in humans, it is therefore necessary to take the bifurcation angle into consideration in the case of LMT stenting. These data suggest that a bifurcation study using MSCT can clarify the 3D structure of coronary bifurcation and may provide useful information for bifurcation stenting.

Impact of a prolonged delivery inflation time for optimal drug-eluting stent expansion.

PURPOSE: We examined the importance of prolonged inflation time for optimal sirolimus-eluting stent (SES) or paclitaxel-eluting stent (PES) expansion. METHODS: Eighty-one de novo lesions deployed single SES or PES between April 2007 and March 2008 were divided into four groups; group 1: 21 SES deployed at 20 atm x 60 sec, group 2: 20 SES deployed with 2-step inflation at 20 atm x 60 sec following 20 atm x 20 sec, group 3: 20 PES deployed same as group 1, group 4: 20 PES deployed same as group 2. The minimal lumen diameter (MLD) and stent expansion ratio (SER; stent cross- sectional area at lesion/balloon cross-sectional area which was calculated according to the compliance chart at the same atmosphere as stent deployment) were compared between group 1 and group 2 in SES, between group 3 and group 4 in PES. RESULTS: The MLD of post 60 sec was significantly higher than that of post 20 sec (2.84 +/- 0.28 mm in group 1, 2.76 +/- 0.33 mm in group 2 vs. 2.54 +/- 0.33 mm in group 2; P = 0.003, 0.045, respectively and 2.94 +/- 0.28 mm in group 3, 3.00 +/- 0.34 mm in group 4 vs. 2.69 +/- 0.35 mm in group 4; P = 0.022, 0.007, respectively). The SER of post 60 sec was significantly higher than that of post 20 sec (79.3% +/- 8.5% in group 1, 80.8% +/- 7.8% in group 2 vs. 71.1% +/- 10.2% in group 2; P = 0.014, 0.011, respectively and 81.1% +/- 7.9% in group 3, 84.3% +/- 9.9% in group 4 vs. 72.6% +/- 10.5% in group 4, P = 0.011, 0.001, respectively). CONCLUSION: The prolonged delivery inflation for 60 sec may result in a more optimal stent expansion. It is therefore considered to be a useful method for deploying drug-eluting stent.

Direct hemoperfusion with polymyxin-B-immobilized fiber columns improves septic hypotension and reduces inflammatory mediators in septic patients with colorectal perforation.

PURPOSE: Although some studies have reported favorable effects of direct hemoperfusion with polymyxin-B-immobilized fiber columns (PMX) for the treatment of septic shock, few studies have demonstrated the efficacy of PMX in studies with a uniform case definition and without any other blood purification techniques. MATERIALS AND METHODS: Fifty-two patients with severe sepsis or septic shock secondary to colorectal perforation were treated with PMX. Hemodynamic alterations and plasma concentrations of endotoxin, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, IL-8, and IL-10 were evaluated following PMX treatment. RESULTS: We observed a significant reduction in plasma endotoxin in the nonsurvivors immediately after PMX treatment compared to before treatment. Systolic blood pressure was markedly increased and circulating levels of IL-1beta, IL-1Ra, and IL-8 were significantly reduced during a 2-h interval of PMX. CONCLUSIONS: Our findings suggested that PMX treatment appears to adsorb endotoxin and also modulates circulating cytokine during a 2-h interval of direct hemoperfusion in septic patients with such condition.

Discrepancy of glutamic acid decarboxylase 65 autoantibody results between RSR radioimmunoassay and enzyme-linked immunosorbent assay in patients with type 1 diabetes is related to autoantibody affinity.

AIM/INTRODUCTION: Autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) are a valuable diagnostic and predictive marker for type 1 diabetes. Recently, it has been reported that a significant proportion of sera in the commercial RSR radioimmunoassay (RIA) that have tested positive for GADA have then turned negative in RSR enzyme-linked immunosorbent assay (ELISA) tests in patients with type 1 diabetes. The present study aimed to investigate whether the GADA result discrepancies between RSR-RIA and RSR-ELISA are related to autoantibody affinity. METHODS: GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 in 12 discordant samples (5 RIA[+]/ELISA[-] and 7 RIA[-]/ELISA[+] sera). Furthermore, the effect of the initial incubation time on the GADA positivity was also examined using the ELISA test. RESULTS: GADA affinities were >1010  L/mol in two of five RIA(+)/ELISA(-) and all of seven RIA(-)/ELISA(+) sera. After an initial incubation time longer than the recommended 1 h, the GADA titer in three of five RIA(+)/ELISA(-) sera and all RIA(-)/ELISA(+) sera increased 1.6- to 100-fold. However, the titer in 12 GADA-negative sera from healthy controls remained unchanged after the longer incubation. The increment ratio of GADA titer was positively correlated with GADA affinity (r = 0.991, P < 0.001). CONCLUSIONS: The RSR-RIA test identifies both high- and low-affinity GADA, whereas the RSR-ELISA test identifies only high-affinity GADA. A longer initial incubation time in the RSR-ELISA test increases the sensitivity of GADA with the same specificity in patients with type 1 diabetes.

Effect of high fiber density ratio polysulfone dialyzer on protein removal.

BACKGROUND/AIMS: A dialyzer (APS-EX) with a higher hollow fiber density ratio was manufactured using the highest performance polysulfone hollow fiber from Asahi-Kasei Medical. METHODS: We compared the performance of this device in comparison with hemodialysis (HD; APS-S) and hemodiafiltration (HDF) conditions (APS-S, 10 l post-HDF) to evaluate its merit as an internal filtration-enhanced dialyzer. RESULTS: With low molecular weight proteins, APS-EX had a reduction ratio of 74.3% for beta(2)-microglobulin (beta(2)-MG), and 31.0% for alpha(1)-MG. APS-EX had a significant higher removal amount of alpha(1)-MG compared to APS-S (HDF). Significant differences were seen in albumin loss, 4.0 g for APS-EX, 3.0 g for APS-S (HDF), and 0.9 g for APS-S (HD). Using HD mode, APS-EX demonstrated a performance which was more than equivalent to approximately 10 l post-HDF. CONCLUSIONS: The results suggested the possibility that HD equivalent to HDF can be performed safely with the ultrapure dialysate when using APS-EX with internal filtration.

Safety and efficacy of liraglutide treatment in Japanese type 2 diabetes patients after acute myocardial infarction: A non-randomized interventional pilot trial.

BACKGROUND: Glucagon-like peptide 1 analogs are expected to exert a cardio-protective action due to their effective glucose-lowering action and favorable potency on multifactorial metabolic pathways. However, the safety and tolerability of liraglutide treatment after a recent acute coronary syndrome (ACS) in Japanese patients with type 2 diabetes mellitus (T2DM) have yet to be fully established. METHODS: A total of eight T2DM patients were recruited within 2 weeks after the onset of a ST-elevation myocardial infarction (STEMI) followed by successful percutaneous coronary intervention (PCI). The patients continued to receive liraglutide (up to 0.9mg once daily) for 24 weeks after the ACS combined with standard treatment such as a statin or beta-blocker. Changes in various metabolic parameters from pre-liraglutide treatment values were evaluated 24 weeks after liraglutide treatment, and included glycemic and lipid profiles, and cardiac systolic and diastolic function assessed by cardiac ultrasonography. RESULTS: Twenty-four weeks of treatment with liraglutide reduced body weight (67.0±5.8kg to 62.0±7.8kg, p=0.003) and HbA1c level (6.6±0.5% to 5.9±0.5%, p=0.006) and increased the level of 1,5-anhydroglucitol (12.8±6.9µg/mL to 18.7±8.2µg/mL, p=0.008) without development of hypoglycemia. There were no significant changes over 24 weeks in left ventricular systolic or diastolic function assessed by cardiac ultrasonography. No participant developed a major adverse cardiac event during the 24 weeks of liraglutide treatment, defined as cardiac death, new onset or recurrence of myocardial infarction, or needing target lesion revascularization. CONCLUSIONS: The present trial demonstrated that liraglutide treatment after onset of STEMI was well-tolerated in Japanese patients with T2DM over 24 weeks, and provided the first evidence to support clinical application of liraglutide treatment even just after ACS in Japanese high-risk T2DM patients.