Clinical outcomes and risk factors associated with drug-coated balloon treatment for femoropopliteal artery disease in patients on maintenance hemodialysis.

The effect of drug-coated balloons (DCB) on hemodialysis (HD) in patients with femoropopliteal (FP) disease remains uncertain. This study aimed to investigate the outcomes of DCB therapy in patients with FP artery disease on HD. A total of 185 patients with FP lesions (140 HD patients) who underwent DCB treatment were included in the study. The incidence of restenosis and target lesion revascularization (TLR) at 12 months were measured. Risk factors for TLR were also investigated. The mean age was 71.7 years, and diabetes was observed in 82.3% of patients. The mean duration of receiving dialysis was 8.8 years. The mean lesion length was 11.0 cm, and approximately half of the lesions were severely calcified. Severe dissection after DCB therapy was observed in 19.5% of patients. During the follow-up period, 74 restenosis, 68 TLRs, 8 major amputations, and 28 deaths were observed. The freedom rates from restenosis and TLR at 12 months were 63.8% and 71.3%, respectively. The freedom rates after low- and high-dose DCB at 12 months were 61.9% and 70.6% for restenosis (P = 0.49) and 66.4% and 79.4% for TLR (P = 0.095), respectively. Independent risk factors for TLR at 12 months of age were diabetes, chronic limb-threatening ischemia, and severe calcification. When patients were divided into four groups according to the number of these three risk factors, the rates of freedom from TLR at 12 months were 100%, 94.8%, 76.7%, and 30.3% in the groups with no risk factors, any one risk factor, any two risk factors, and all risk factors, respectively (P < 0.0001). Clinical outcomes after endovascular therapy in HD patients with FP disease remain unsatisfactory, even if they are treated with DCB. In particular, patients on HD with diabetes, chronic limb-threatening ischemia, and severe calcification have poor outcomes.

Development and evaluation of a rapid one-step high sensitivity real-time quantitative PCR system for minor BCR-ABL (e1a2) test in Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).

OBJECTIVE: Minimal residual disease assessment of BCR-ABL messenger ribonucleic acid levels is crucial in Philadelphia chromosome-positive acute lymphoblastic leukemia for prognosis and treatment planning. However, accurately quantifying minor BCR-ABL transcripts, which comprise 70% of Philadelphia chromosome-positive acute lymphoblastic leukemia cases, lacks a national-approved method. METHODS: We developed the "Otsuka" minor BCR-ABLmessenger ribonucleic acid assay kit with exceptional precision (0.00151%). Minor BCR-ABL messenger ribonucleic acid levels were analyzed in 175 adults, 36 children with acute lymphoblastic leukemia and 25 healthy individuals to evaluate the kit's performance. RESULTS: The "Otsuka" kit showed high concordance with a commonly used chimeric gene screening method, indicating reliable detection of positive cases. Quantitative results demonstrated a robust correlation with both a laboratory-developed test and a diagnostic research product. The "Otsuka" kit performs comparably or even surpass to conventional products, providing valuable insights into Philadelphia chromosome-positive acute lymphoblastic leukemia pathology. CONCLUSIONS: The 'Otsuka" minor BCR-ABL messenger ribonucleic acid assay kit exhibits excellent performance in quantifying minor BCR-ABL transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Our results align well with established screening methods and show a strong correlation with laboratory-developed tests and diagnostic research products. The "Otsuka" kit holds great promise as a valuable tool for understanding Philadelphia chromosome-positive acute lymphoblastic leukemia pathology and guiding effective treatment strategies.

Drug-coated balloons versus drug-eluting stents for coronary de novo lesions in dialysis patients.

BACKGROUND: The aim of this study was to compare the efficacy of drug-coated balloon (DCB) angioplasty with drug-eluting stent (DES) angioplasty in the treatment of de novo coronary artery lesions in dialysis patients. METHOD: We retrospectively enrolled 400 consecutive dialysis patients with 464 coronary de novo lesions treated by DCB or DES from five participating institutions in Japan. The primary endpoint was target lesion revascularization (TLR) at 12 months. We performed serial coronary angiographic analysis. RESULTS: There were no significant differences in the rate of TLR between the groups in either crude or propensity score-matched analysis (DES 14.1% vs. DCB 14.7%, P = 0.864, DES 12.1% vs. 12.1%, P = 1.00). Target lesion thrombosis was not observed in the DCB group; however, stent thrombosis was observed in 7 patients (2.2%) in the DES group. The rate of binary restenosis was similar in both groups (DES, 20.9% vs. DCB, 22.8%; P = 0.749). The late lumen loss at follow-up was significantly greater in the DES group than in the DCB group (0.61 ± 0.76 mm vs 0.22 ± 0.48 mm; P < 0.001). Late lumen enlargement was observed in 38.6% of patients in the DCB group. CONCLUSION: The efficacy of DCB angioplasty for de novo coronary artery lesions in dialysis patients was similar to that of DES angioplasty in the real world. Drug-coated balloon angioplasty can be an acceptable treatment for de novo coronary artery lesions in dialysis patients.

Combined Prognostic Value of Preprocedural Protein-Energy Wasting and Inflammation Status for Amputation and/or Mortality after Lower-Extremity Revascularization in Hemodialysis Patients with Peripheral Arterial Disease.

Protein-energy wasting is associated with inflammation and advanced atherosclerosis in hemodialysis patients. We enrolled 800 patients who had undergone successful lower-extremity revascularization, and we investigated the association among the Geriatric Nutritional Risk Index (GNRI) as a surrogate marker of protein-energy wasting, C-reactive protein (CRP), and their joint roles in predicting amputation and mortality. They were divided into lower, middle, and upper tertiles (T1, T2, and T3) according to GNRI and CRP levels, respectively. Regarding the results, the amputation-free survival rates over 8 years were 47.0%, 56.9%, and 69.5% in T1, T2, and T3 of the GNRI and 65.8%, 58.7%, and 33.2% for T1, T2, and T3 of CRP, respectively (p < 0.0001 for both). A reduced GNRI [adjusted hazard ratio (aHR) 1.78, 95% confidence interval (CI) 1.24-2.59, p = 0.0016 for T1 vs. T3] and elevated CRP (aHR 1.86, 95% CI 1.30-2.70, p = 0.0007 for T3 vs. T1) independently predicted amputation and/or mortality. When the two variables were combined, the risk was 3.77-fold higher (95% CI 1.97-7.69, p < 0.0001) in patients who occupied both T1 of the GNRI and T3 of CRP than in those who occupied both T3 of the GNRI and T1 of CRP. In conclusion, patients with preprocedurally decreased GNRI and elevated CRP levels frequently experienced amputation and mortality, and a combination of these two variables could more accurately stratify the risk.

Association of resting left ventricular global longitudinal strain with myocardial perfusion abnormalities evaluated by 13 N-ammonia positron emission tomography in patients with stable angina pectoris and normal left ventricular ejection fraction.

AIMS: Little is known about whether resting left ventricular global longitudinal strain (GLS) impairment is associated with myocardial perfusion abnormalities evaluated using 13 N-ammonia positron emission tomography (13 N-NH3 -PET)-myocardial perfusion imaging (MPI). This study aimed to investigate the correlation between resting GLS and myocardial perfusion parameters in patients with a normal left ventricular ejection fraction (LVEF). We evaluated whether resting GLS can predict myocardial perfusion abnormalities in these patients. METHODS AND RESULTS: We selected 157 patients with suspected stable angina pectoris who underwent both ATP-stress NH3 -PET-MPI and 2-dimentional speckle tracing echocardiography. All subjects had a preserved LVEF and no known history of myocardial infarction. Patients were stratified into Group N (normal perfusion; summed stress score [SSS], 0-3; n = 101), Group M (mildly to moderately abnormal perfusion; SSS, 4-11; n = 41), or Group S (severely abnormal perfusion; SSS, 12+; n = 15). GLS was more impaired as myocardial perfusion abnormality severity increased (-17.9 ± 2.9% for Group N, -16.8 ± 3.1% for Group M, and -14.2 ± 3.5% for Group S; p < .001). GLS was weakly but significantly correlated with SSS (R = .32, p < .001), summed difference score (R = .32, p < .001), and myocardial blood flow during stress (R = -0.27, p < .001). Multivariate logistic regression analysis showed that male sex, diabetes mellitus, systolic blood pressure, and GLS were independent predictors of myocardial perfusion abnormality defined as Groups M and S. Additionally, the area under the curve for GLS for detecting myocardial perfusion abnormality was .65, and the optimal cutoff value for GLS was -16.5%, with sensitivity and specificity of 59% and 66%, respectively. CONCLUSION: In patients with suspected angina pectoris, resting GLS impairment despite a normal LVEF might aid the detection of hemodynamically significant coronary artery disease.

Impact of Hemodialysis on Clinical Outcomes in Patients Undergoing Lower Extremity Bypass Surgery for Peripheral Artery Disease-10-year Follow-Up Study.

We investigated the clinical impact of hemodialysis on long-term outcomes of bypass surgery in patients with peripheral artery disease. We evaluated 660 consecutive patients who underwent successful bypass surgery (392 hemodialysis and 268 non-hemodialysis). The endpoint was amputation-free survival (AFS). To minimize differences in clinical characteristics between the 2 groups, propensity score matching was performed. The AFS rates for 10-year follow-up were 39.3% and 67.7% in hemodialysis and non-hemodialysis patients [hazard ratio (HR) 2.21, 95% confidence interval (CI) 1.65-3.01, P < .0001]. Cumulative incidence of amputation was higher in the hemodialysis group than in the non-hemodialysis group [(19.4 vs 8.4%, HR 2.15, 95% CI 1.29-3.74, P = .0027). In a matched cohort (n = 210 each), AFS was still lower in the hemodialysis patients (53.1 vs 66.3%, HR 1.94, 95% CI 1.36-2.82, P = .0003). However, there was no significant difference in amputation rate between the groups (10.5 vs 10.6%, HR .97, 95% CI 0.49-1.87, P = .93). In a sub-analysis of patients with critical limb ischemia, similar results were obtained. The 10-year AFS was consistently lower in the hemodialysis group than in the non-hemodialysis group. However, the amputation rate was comparable between the groups when matched for the differences in clinical characteristics.

Comparison between biodegradable- and durable-polymer everolimus-eluting stents in hemodialysis patients with coronary artery disease.

To investigate the clinical outcomes after biodegradable-polymer (BP) and durable-polymer (DP) everolimus-eluting stent (EES) implantation in hemodialysis (HD) patients with coronary artery disease. We enrolled 221 consecutive HD patients successfully treated with EES implantation for coronary lesions. Over the following 2 years, we assessed the incidence of target lesion revascularization (TLR) and major adverse cardiac event (MACE), defined as the composite endpoint of TLR, all-cause mortality, or myocardial infarction. We performed a propensity-score matching analysis and collected follow-up coronary angiography data. There were 91 patients in the BP-EES group and 130 in the DP-EES group. Male sex and diabetes rates were significantly lower in the BP-EES group than in the DP-EES group. A debulking device was less frequently used in the BP-EES group than in the DP-EES group (7.6% vs. 21.5%, p = 0.006). TLR occurred in 38 patients, while stent thrombosis was observed in 3 patients; 19 patients died. TLR and MACE rates at 2 years were comparable between the two groups (19.2% in the BP-EES group vs. 20.4% in the DP-EES group, p = 0.73 and 26.9% vs. 34.2%, p = 0.93, respectively). In the propensity-score-matched cohort, TLR and MACE rates were similar between the two groups (19.2% in the BP-EES group vs. 18.1% in the DP-EES group, p = 0.69, and 26.9% vs. 30.2%, p = 0.66, respectively). Restenosis rates at follow-up angiography were similar between the two groups (p = 0.79). In hemodialysis patients, BP-EES and DP-EES showed similar 2-year clinical outcomes.

Outcomes after drug-coated balloon interventions for de novo coronary lesions in the patients on chronic hemodialysis.

The impact of drug-coated balloon (DCB) on hemodialysis (HD) patients with coronary lesions remains unclear. This study aimed to compare outcomes after DCB treatment between HD and non-HD patients with de novo coronary lesions. A total of 235 consecutive patients who electively underwent DCB treatment for de novo coronary lesions were included (HD group: n = 100; non-HD group: n = 135). Angiographic follow-up was performed 6 months after the procedure. Patients were clinically followed up for 2 years. The incidence rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) were investigated. Diabetes and a history of coronary bypass grafting were more frequent in the HD group than in the non-HD group (69.0% vs. 50.7%, p = 0.007, and 24.0% vs 9.1%, p = 0.013, respectively). The reference diameter and pre-procedural diameter stenosis were greater in the HD group than in the non-HD group (2.49 mm vs. 2.24 mm, p = 0.007, and 65.9% vs. 59.6%, p = 0.015, respectively). Calcification was observed in 65.5% of all lesions, and rotational atherectomy was performed in 30.2% patients. The average diameter of the DCB was 2.51 mm (2.57 mm, HD group vs. 2.47 mm, non-HD group, p = 0.14). Although post-procedural diameter stenosis was similar between the groups, late lumen loss on follow-up angiography was larger in HD patients than in non-HD patients (0.27 mm vs. - 0.03 mm, p = 0.0009). The 2-year rates of freedom from TLR and MACE were lower in HD patients than in non-HD patients [79.3% vs. 91.7%, hazard ratio (HR) 2.76, 95% confidence interval (CI) 1.23-6.77, p = 0.014; and 61.6% vs. 89.4%, HR 4.60, 95% CI 2.30-10.2, p < 0.001, respectively]. In conclusion, the rates of TLR and MACE after DCB treatment were higher in HD patients than in non-HD patients.

Histologic Distribution and Characteristics on MR Imaging of Ultrasmall Superparamagnetic Iron Oxide in Ethyl-nitrosourea-induced Endogenous Rat Glioma.

PURPOSE: (1) To evaluate the enhancement patterns of an ultrasmall superparamagnetic iron oxide contrast agent (USPIO-CA) compared with those of a gadolinium-based contrast agent (Gd-BCA). (2) To compare the histologic distribution of USPIO-related iron particles (USPIO-IPs) with the USPIO-enhancement area in the early vascular and in the cellular imaging phase (E- and L-phase, respectively) after intravenous CA administration. METHODS: We performed USPIO-enhanced MRI of N-ethyl-N-nitrosourea (ENU)-induced endogenous rat glioma, including spin-echo (SE) T1-weighted images (T1WIs) and gradient-recalled-echo (GRE) T2-weighted images (T2WIs), before and at 3-6 h after USPIO-CA administration for E-phase images. For L-phase images, MRI was performed at 16-19 and 62-69 h after administration. Two observers determined the USPIO-enhancement area on E-phase images and Gd-enhancement areas. We compared the USPIO-enhancement size (USPIO-ES) and Gd-ES on SE T1WIs, and the hypo-intense USPIO-ES on GRE T2WIs and Gd-ES using the Wilcoxon signed-rank test. In addition, two raters visually evaluated the correspondence between the histologic distribution of USPIO-IPs and the USPIO-enhancement area on corresponding GRE T2WIs at each phase using a 3-rating scale. RESULTS: Significantly smaller hyper-intense, hypo-intense and combined hyper-/hypo-intense areas were observed on USPIO-enhanced SE T1WIs compared with Gd-enhanced images (all P < 0.001). The hypo-intense USPIO-ES on GRE T2WIs was significantly smaller than the Gd-ES (P = 0.001). The distribution of USPIO-IPs on histopathological specimen and USPIO-enhancement on GRE T2WIs exhibited poor agreement in 5 of 9 tumors with enhancement from rats sacrificed early. The distribution of microglia containing USPIO-IPs corresponded with the pattern of USPIO-enhancement in the 2 tumors with late enhancement. CONCLUSION: The enhancement pattern and size of USPIO-CA in a rat glioma model were statistically different from those of Gd-BCA. Our histological data suggests that USPIO-enhanced MRI offers vascular bed imaging in E-phase and might depict the intra-tumoral distribution of immune effector cells in L-phase.

Long-term clinical outcomes after self-expandable bare nitinol stent implantation for femoropopliteal occlusive disease in hemodialysis patients.

OBJECTIVES: To compare the long-term clinical outcomes after self-expandable bare nitinol stent (BNS) implantation between hemodialysis (HD) and non-HD patients with femoropopliteal (FP) disease. BACKGROUND: Although a BNS has been commonly used in patients with FP disease, the long-term efficacy of BNSs in HD patients remains unknown. METHODS: In total, 427 HD patients treated with a BNS for FP disease were enrolled, along with 157 non-HD patients as a control group. Over the following 5 years, the incidence of target lesion revascularization (TLR), major amputation and mortality was investigated. We also performed propensity-score matching analysis. RESULTS: The 5-year TLR rate (45.2 vs. 32.5%, p = .013) and mortality rate (39.3 vs. 14.0%, p = .0002) were significantly higher in the HD group than in the non-HD group. The major amputation rate was comparable between the groups (7.2% in the HD group vs. 2.8% in the non-HD group, p = .16). In the propensity-score-matched cohort, the TLR rate, and mortality rate were remained higher in the HD group than in the non-HD group (48.9 vs. 34.1%, hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.30-3.49, p = .0024, and 47.9 vs. 12.0%, HR 3.38, 95% CI 1.86-6.56, p < .0001, respectively). The adjusted amputation rate was consistently similar between the groups (1.7% in the HD group vs. 2.7% in the non-HD group, HR 0.90, 95% CI 0.26-2.99, p = .86). CONCLUSIONS: The TLR rate and mortality at 5 years post BNS implantation for FP disease were significantly higher in HD patients than in non-HD patients, though the limb salvage rate was similar.

Association of protein-energy wasting and inflammation status with mortality after coronary revascularisation in patients on haemodialysis.

OBJECTIVE: Protein-energy wasting is associated with chronic inflammation and advanced atherosclerosis in haemodialysis (HD) patients. We investigated association of geriatric nutritional risk index (GNRI), C reactive protein (CRP) with prediction of mortality after coronary revascularisation in chronic HD patients. METHODS: We enrolled 721 HD patients electively undergoing coronary revascularisation. They were divided into tertiles according to preprocedural GNRI levels (tertile 1 (T1):<91.5, T2: 91.5-98.1 and T3:>98.1) and CRP levels (T1:≤1.4 mg/L, T2: 1.5-7.0 mg/L and T3:≥7.1 mg/L). RESULTS: Kaplan-Meier 10 years survival rates were 32.3%, 44.8% and 72.5% in T1, T2 and T3 of GNRI and 60.9%, 49.2% and 23.5% in T1, T2 and T3 of CRP, respectively (p<0.0001 in both). Declined GNRI (HR 2.40, 95% CI 1.58 to 3.74, p<0.0001 for T1 vs T3) and elevated CRP (HR 2.31, 95% CI 1.58 to 3.43, p<0.0001 for T3 vs T1) were identified as independent predictors of mortality. In combined setting of both variables, risk of mortality was 5.55 times higher (95% CI 2.64 to 13.6, p<0.0001) in T1 of GNRI with T3 of CRP than in T3 of GNRI with T1 of CRP. Addition of GNRI and CRP in a model with established risk factors improved C-statistics (0.648 to 0.724, p<0.0001) greater than that of each alone. CONCLUSION: Preprocedural declined GNRI and elevated CRP were closely associated with mortality after coronary revascularisation in chronic HD patients. Furthermore, combination of both variables not only stratified risk of mortality but also improved the predictability.

Machine Learning for Diagnosis of AD and Prediction of MCI Progression From Brain MRI Using Brain Anatomical Analysis Using Diffeomorphic Deformation.

Background: With the growing momentum for the adoption of machine learning (ML) in medical field, it is likely that reliance on ML for imaging will become routine over the next few years. We have developed a software named BAAD, which uses ML algorithms for the diagnosis of Alzheimer's disease (AD) and prediction of mild cognitive impairment (MCI) progression. Methods: We constructed an algorithm by combining a support vector machine (SVM) to classify and a voxel-based morphometry (VBM) to reduce concerned variables. We grouped progressive MCI and AD as an AD spectrum and trained SVM according to this classification. We randomly selected half from the total 1,314 subjects of AD neuroimaging Initiative (ADNI) from North America for SVM training, and the remaining half were used for validation to fine-tune the model hyperparameters. We created two types of SVMs, one based solely on the brain structure (SVMst), and the other based on both the brain structure and Mini-Mental State Examination score (SVMcog). We compared the model performance with two expert neuroradiologists, and further evaluated it in test datasets involving 519, 592, 69, and 128 subjects from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Aging (AIBL), Japanese ADNI, the Minimal Interval Resonance Imaging in AD (MIDIAD) and the Open Access Series of Imaging Studies (OASIS), respectively. Results: BAAD's SVMs outperformed radiologists for AD diagnosis in a structural magnetic resonance imaging review. The accuracy of the two radiologists was 57.5 and 70.0%, respectively, whereas, that of the SVMst was 90.5%. The diagnostic accuracy of the SVMst and SVMcog in the test datasets ranged from 88.0 to 97.1% and 92.5 to 100%, respectively. The prediction accuracy for MCI progression was 83.0% in SVMst and 85.0% in SVMcog. In the AD spectrum classified by SVMst, 87.1% of the subjects were Aß positive according to an AV-45 positron emission tomography. Similarly, among MCI patients classified for the AD spectrum, 89.5% of the subjects progressed to AD. Conclusion: Our ML has shown high performance in AD diagnosis and prediction of MCI progression. It outperformed expert radiologists, and is expected to provide support in clinical practice.

Safety and Long-Term Efficacy of Drug-Coated Balloon Angioplasty following Rotational Atherectomy for Severely Calcified Coronary Lesions Compared with New Generation Drug-Eluting Stents.

OBJECTIVES: This study sought to assess the safety and long-term efficacy of drug-coated balloons (DCB) following aggressive intracoronary image-guided rotational atherectomy (iRA) for severe coronary artery calcification (CAC), and to compare this strategy with new generation drug-eluting stents (nDES) following iRA. BACKGROUND: Ischemic events following the treatment of CAC is still relatively high. Thus, more innovative strategies are required. METHODS: We evaluated 123 consecutive patients (166 lesions) with de novo CAC undergoing an iRA (burr size; 0.7 of the mean reference diameter by intracoronary imaging) followed by DCB (DCB-iRA; 54 patients, 68 lesions) or nDES (nDES-iRA; 69 patients, 98 lesions). Follow-up angiography was obtained at > 6 months. RESULTS: The target vessels (right coronary and circumflex), bifurcation (67.6% versus 47.9%), reference diameter (2.28mm versus 2.49mm), and lesion length (11.89mm versus 18.78mm) were significantly different between the two groups. The median follow-up was 732 days. TLR and TVR in DCB-iRA and nDES-iRA at 3 years were similar: 15.6% versus 16.3% (P=0.99) and 15.6% versus 23.3% (P=0.38). In 41 well-matched lesion pairs after propensity score analysis, the cumulative incidence of TLR and TVR in DCB-iRA and nDES-iRA at 3 years was 12.9% versus 16.3% (P=0.70) and 12.9% versus 26.1% (P=0.17), respectively. On QCA analysis, although the acute gain was smaller in DCB-iRA (0.85 mm versus 1.53 mm, P<0.001), the minimum lumen diameter at follow-up was similar (1.69 mm versus 1.87 mm, P=0.29). The late lumen loss was lower (0.09 mm versus 0.52 mm, P=0.009) in DCB-iRA. CONCLUSIONS: DCB-iRA is feasible for CAC.

Lipoarabinomannan in sputum to detect bacterial load and treatment response in patients with pulmonary tuberculosis: Analytic validation and evaluation in two cohorts.

BACKGROUND: Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB). In this report, we evaluated the ability of a novel immunoassay to measure concentrations of LAM in sputum as a biomarker of bacterial load prior to and during treatment in pulmonary tuberculosis (TB) patients. METHODS AND FINDINGS: Phage display technology was used to isolate monoclonal antibodies binding to epitopes unique in LAM from MTB and slow-growing nontuberculous mycobacteria (NTM). Using these antibodies, a sandwich enzyme-linked immunosorbent assay (LAM-ELISA) was developed to quantitate LAM concentration. The LAM-ELISA had a lower limit of quantification of 15 pg/mL LAM, corresponding to 121 colony-forming units (CFUs)/mL of MTB strain H37Rv. It detected slow-growing NTMs but without cross-reacting to common oral bacteria. Two clinical studies were performed between the years 2013 and 2016 in Manila, Philippines, in patients without known human immunodeficiency virus (HIV) coinfection. In a case-control cohort diagnostic study, sputum specimens were collected from 308 patients (aged 17-69 years; 62% male) diagnosed as having pulmonary TB diseases or non-TB diseases, but who could expectorate sputum, and were then evaluated by smear microscopy, BACTEC MGIT 960 Mycobacterial Detection System (MGIT) and Lowenstein-Jensen (LJ) culture, and LAM-ELISA. Some sputum specimens were also examined by Xpert MTB/RIF. The LAM-ELISA detected all smear- and MTB-culture-positive samples (n = 70) and 50% (n = 29) of smear-negative but culture-positive samples (n = 58) (versus 79.3%; 46 positive cases by the Xpert MTB/RIF), but none from non-TB patients (n = 56). Among both LAM and MGIT MTB-culture-positive samples, log10-transformed LAM concentration and MGIT time to detection (TTD) showed a good inverse relationship (r = -0.803, p < 0.0001). In a prospective longitudinal cohort study, 40 drug-susceptible pulmonary TB patients (aged 18-69 years; 60% male) were enrolled during the first 56 days of the standard 4-drug therapy. Declines in sputum LAM concentrations correlated with increases of MGIT TTD in individual patients. There was a 1.29 log10 decrease of sputum LAM concentration, corresponding to an increase of 221 hours for MGIT TTD during the first 14 days of treatment, a treatment duration often used in early bactericidal activity (EBA) trials. Major limitations of this study include a relatively small number of patients, treatment duration up to only 56 days, lack of quantitative sputum culture CFU count data, and no examination of the correlation of sputum LAM to clinical cure. CONCLUSIONS: These results indicate that the LAM-ELISA can determine LAM concentration in sputum, and sputum LAM measured by the assay may be used as a biomarker of bacterial load prior to and during TB treatment. Additional studies are needed to examine the predictive value of this novel biomarker on treatment outcomes.

Long-term clinical outcomes after coronary artery bypass graft versus everolimus-eluting stent implantation in chronic hemodialysis patients.

BACKGROUND: It remains controversial whether coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) should be optimized to treat coronary artery disease in patients on chronic hemodialysis (HD). Recently, further refinement of drug-eluting stents, such as the everolimus-eluting stent (EES), has led to marked development in this field. We compared long-term clinical outcomes after CABG versus PCI with EES implantation in patients on chronic HD. PATIENTS AND METHODS: We compared 138 patients undergoing CABG and 187 patients treated with EES implantation. The endpoint was major adverse cardiac events (MACE) as a composite outcome, including any revascularization, nonfatal myocardial infarction, or mortality. To reduce the selection bias for the two procedures, propensity score-matching was performed. RESULTS: During the follow-up period (43 months), 95 (29.2%) MACEs, including 43 (13.2%) revascularizations, 14 (4.3%) nonfatal myocardial infarctions, and 63 (19.4%) deaths, occurred. The freedom rate from MACE and mortality at 5 years were comparable between groups (69.7 vs. 66.7%, P=0.82 and 75.0 vs. 80.6%, P=0.10, respectively); however, those from revascularization at 5 years was higher in the CABG group than the EES group (89.4 vs. 81.0%, P=0.030). In propensity score-matched patients (n=92), the freedom rate from revascularization at 5 years was still higher in the CABG group than in the EES group (93.4 vs. 79.1%, P=0.013). Similarly, the freedom rates from MACE and mortality were comparable (70.0 vs. 66.3%, P=0.69 and 73.8 vs. 79.7%, P=0.30, respectively). CONCLUSION: Even in the second-generation drug-eluting stent era, CABG is still superior for preventing revascularization in patients on chronic HD. However, PCI with EES implantation might not have disadvantages compared with CABG in terms of MACE.

Clinical Outcomes after Isolated Infrapopliteal Revascularization in Hemodialysis Patients with Critical Limb Ischemia: Endovascular Therapy versus Bypass Surgery.

AIM: To investigate the long-term clinical outcome of endovascular therapy (EVT) or bypass surgery in patients on hemodialysis (HD) with critical limb ischemia due to isolated infrapopliteal disease. METHODS: We enrolled 254 consecutive HD patients successfully undergoing infrapopliteal revascularization by EVT (126 patients) and bypass surgery (128 patients). They were followed up for five years. Amputation-free survival (AFS) and incidence of any re-intervention were evaluated. A propensity score from all baseline variables was incorporated into Cox analysis. RESULTS: In the EVT group, age was higher (p=0.039), diabetes and coronary artery disease were more frequent (p=0.004 and p=0.0052, respectively), and tissue loss was more rarely observed (p＜ 0.0001) than in the bypass group. During the follow-up period, 21 major amputations and 64 deaths occurred. The propensity score-adjusted AFS rate at 5 years was comparable between groups (61.0% in EVT group vs. 55.1% in the bypass group, adjusted hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.52-1.42, p=0.58). The adjusted survival rates were also similar between groups for amputation and all-cause mortality. However, freedom from any re-intervention was markedly lower in the EVT than in the bypass group (48.6% vs. 84.6%, adjusted-HR, 3.56, 95% CI 1.95-6.75, p＜ 0.0001). CONCLUSIONS: The rate of AFS was broadly comparable between the two strategies, although compared with bypass surgery, EVT had much higher rates for re-intervention.

Outcomes after drug-coated balloon treatment for patients with calcified coronary lesions.

OBJECTIVES: To investigate the efficacy of drug-coated balloon (DCB) for calcified coronary lesions. BACKGROUND: Calcified coronary lesions is associated with poor clinical outcomes after revascularization. Recently, DCB is emerging as an alternative strategy for de novo coronary lesions. However, reports describing the efficacy of DCB for calcified coronary lesions are limited. METHODS: A total of 81 patients (96 lesions) who electively underwent DCB treatment for de novo coronary lesions were enrolled: 46 patients (55 lesions) in the calcified group and 35 patients (41 lesions) in the non-calcified group. Angiographic follow-up data and clinical outcomes after the procedure were evaluated. RESULTS: The diameter of the DCB used was 2.5 ± 0.5 mm. No bail-out stenting was observed after DCB treatment. Rotational atherectomy was used in 82% of lesions in the calcified group. Follow-up angiography (median, 6.5 months after intervention) was performed for 59 patients (30 in the calcified group and 29 in the non-calcified group). Late lumen loss and rates of restenosis were comparable between the groups (0.03 mm in the calcified group vs -0.18 mm in the non-calcified group, P = 0.093 and 13.9% vs 3.03%, P = 0.095, respectively). The survival rates for target lesion revascularization free survival and major adverse cardiac events at 2 years were comparable between the groups (85.3% vs 93.4%, P = 0.64 and 81.4% vs 88.5%, P = 0.57, respectively). CONCLUSION: Calcified coronary lesions might dilute the effect of DCB. However, clinical outcomes in the calcified group were similar to those in the non-calcified group.

Investigation of association between TLR9 gene polymorphisms and VKH in Japanese patients.

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disorder affecting melanocytes in the skin, eyes, inner ear, and meninges. The Epstein-Barr virus and cytomegalovirus (CMV) antigen have been hypothesized as possible triggering factors for the disease. Toll-like receptors (TLRs) play an important role in the induction of defense mechanisms of the innate and adaptive immune responses to microbial pathogens. Among TLRs, TLR9 recognizes unmethylated 2'-deoxyribo (cytidine-phosphate guanosine)(CpG) DNA motifs that are frequently present in viruses and plays a central role in the host defense against viral infection. The aim of this study was to investigate whether TLR9 polymorphisms were associated with VKH in a Japanese population. METHODS: Ninety-four Japanese patients diagnosed with VKH and 125 healthy control subjects were recruited. Five single-nucleotide polymorphisms (SNPs: rs187084, rs5743836, rs352139, rs352140, rs5743845) in the TLR9 gene were genotyped, and allelic and phenotypic diversity was assessed between cases and control subjects. RESULTS: Strong linkage disequilibrium was observed among three SNPs (D' > 0.99), which were located in one haplotype block. Two SNPs (rs5743836 and rs5743845) were monopolymorphic in both cases and controls. No statistically significant association was observed for any of the SNPs between cases and controls. CONCLUSION: Three SNPs in the TLR9 gene were not significantly associated with susceptibility to VKH.

[The measurement of fractional anisotropy values at the corpus callosum in an irradiated-rat model by 7T-MRI: comparison with quantitative histological evaluation].

Radiation-induced white matter injury has recently been evaluated by fractional anisotropy (FA) values using diffusion tensor image (DTI) data on magnetic resonance (MR) imaging. However, controversy remains as to which histological components affect anisotropy. FA values were compared with histological findings in rat irradiated brains. Forty Gy whole brain radiation was performed on 9 rats, with another 9 rats not subjected to irradiation prepared as the control group. DTI data for the corpus callosum were obtained using a 7.0 Tesla MR scanner at post radiation 18+2 to 48 +/- 2 weeks (p18w-p48w), and the mean FA value (mFA) was calculated. Histological parameters were assessed at p24w, p36w, and p48w in hematoxylin-eosin stained and immunohistochemically processed sections. Numbers of dilated vessels, hypertrophic glial fibrillary acidic protein (GFAP)-positive cells and Olig2-positive cells were quantitatively evaluated. Qualitative assessment of change in neurofilament (NF)-and myelin basic protein (MBP)-positive structures at each time point was also performed. The mFA decreased from p30w to p42w, significantly decreasing at p42w compared to the control group. However, It recovered to control levels at p48w. Histological examination showed that hypertrophic GFAP-positive cells and dilated vessels had increased at p48w. Olig2-positive cells decreased significantly at p48w compared to p24w and p36w (p<0.05). Although NF-positive structures continued to decrease over time, MBP-positive structures recovered at p48w in agreement with the change in mFA. In the subacute/chronic stage, rat irradiated brain FA value in the corpus callosum appears to mainly reflect the change in myelin structure.