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1.
Ann Thorac Surg ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32151581

RESUMO

We report a case of a 23-day-old girl who presented with repeated life-threatening myocardial ischemia from intermittent aortic insufficiency due to fixation of the left coronary cusp against the aortic wall. The patient underwent aortic valve repair with partial commissuroplasty of the left-right and left-non commissures. Following the surgical intervention, the patient has been well, with no ischemic event for over 1 year. This diagnosis should be considered as a differential diagnosis in pediatric cases with myocardial ischemia. Although myocardial ischemia in early infancy is rare, it is potentially life threatening. Early diagnosis is pivotal to prevent irreversible cardiac dysfunction and/or death. The causes of myocardial ischemia include coronary arterial lesions, coronary ostial lesions, and embolisms (1, 2). Diagnosing the cause of myocardial ischemia is integral to the planning of a precise treatment strategy. Here, we report an extremely rare case of a 23-day-old girl with life-threatening myocardial ischemia due to intermittent aortic insufficiency (AI).

2.
Radiographics ; : 190121, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32196428

RESUMO

Relapsing level of prostate-specific antigen (PSA) after initial curative-intent local therapy for organ-confined prostate cancer is often the first sign of recurrence. However, PSA level recurrence does not enable accurate differentiation of locally recurrent tumor from metastatic disease or a combination of both. Metastatic prostate cancer most frequently involves bones and lymph nodes, followed by other organs such as the liver, lung, pleura, adrenal gland, ureter, peritoneum, penis, testis, and meninges. Conventional imaging including CT and bone scintigraphy has long been the standard of care but has limited sensitivity in depicting early local recurrence or metastatic disease. Multiparametric MRI has been shown to be more sensitive in detecting locally recurrent tumor in the prostatectomy bed as well as in situ recurrence in a prostate gland that has been treated with radiation therapy or thermal ablation. In addition, lesions detected with multiparametric MRI may be amenable to targeted biopsy for definitive diagnosis of recurrence. PET/CT or PET/MRI using the U.S. Food and Drug Administration (FDA)-approved tracers carbon 11 choline or fluorine 18 fluciclovine has demonstrated markedly increased sensitivity and specificity for diagnosis of early metastatic disease such as small-volume lymph node metastasis, as have a range of investigational gallium 68 prostate-specific membrane antigen (PSMA) radioactive PET tracers. With recent advances in imaging modalities and techniques, more accurate early detection, localization, and characterization of recurrent prostate cancer have become possible. The authors present a contemporary review of the strengths and limitations of conventional and advanced imaging modalities in evaluation of patients with recurrent prostate cancer and a systematic review of the clinical and imaging features of locally recurrent and metastatic disease.©RSNA, 2020.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32111355

RESUMO

Plasmacytoid dendritic cells (pDCs) are characterized by an exclusive expression of nucleic acid sensing Toll-like receptor 7 (TLR7) and TLR9, and production of high amounts of type I interferon (IFN) in response to TLR7/9 signaling. This function is crucial for both antiviral immunity and the pathogenesis of autoimmune diseases. An Ets family transcription factor, i.e., Spi-B (which is highly expressed in pDCs) is required for TLR7/9 signal-induced type I IFN production and can transactivate IFN-α promoter in synergy with IFN regulatory factor-7 (IRF-7). Herein, we analyzed how Spi-B contributes to the transactivation of the Ifna4 promoter. We performed deletion and/or mutational analyses of the Ifna4 promoter and an electrophoretic mobility shift assay (EMSA) and observed an Spi-B binding site in close proximity to the IRF-7 binding site. The EMSA results also showed that the binding of Spi-B to the double-stranded DNA probe potentiated the recruitment of IRF-7 to its binding site. We also observed that the association of Spi-B with transcriptional coactivator p300 was required for the Spi-B-induced synergistic enhancement of the Ifna4 promoter activity by Spi-B. These results clarify the molecular mechanism of action of Spi-B in the transcriptional activation of the Ifna4 promoter.

4.
Molecules ; 25(5)2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32110993

RESUMO

Amariin is an ellagitannin with two dehydrohexahydroxydiphenoyl (DHHDP) moieties connecting glucose 2,4- and 3,6-hydroxy groups. This tannin is predominant in the young leaves of Triadica sebifera and Carpinus japonica. However, as the leaves grow, the 3,6-DHHDP is converted to its reduced form, the hexahydroxydiphenoyl (HHDP) group, to generate geraniin, a predominant ellagitannin of the matured leaves. The purified amariin is unstable in aqueous solution, and the 3,6-(R)-DHHDP is spontaneously degraded to give HHDP, whereas 2,4-(R)-DHHDP is stable. The driving force of the selective reduction of the 3,6-DHHDP of amariin is shown to be the conformational change of glucose from O,3B to 1C4. Heating geraniin with pyridine affords 2,4-(R)-DHHDP reduction products. Furthermore, the acid hydrolysis of geraniin yields two equivalents of ellagic acid. Although the reaction mechanism is still ambiguous, these results propose an alternative biosynthetic route of the ellagitannin HHDP groups.

5.
J Nat Prod ; 83(2): 413-421, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004001

RESUMO

Vescalagin (1) is a major ellagitannin from young spring leaves of Quercus glauca; however, the amount of 1 decreases as the leaves mature with a concomitant rise in the levels of catechin (3) and procyanidins. In this report, the chemical mechanism responsible for the degradation of 1 was investigated. In vitro model experiments indicated that initially a polyphenol oxidase oxidizes the catechin B-ring, and the resulting catechin o-quinone oxidizes one of the pyrogallol rings of 1 to give a cyclopenten-1,2-dione-type product 4. The presence of 4 in young oak leaves was confirmed by the detection of 4 and its quinoxaline derivative 4a. Furthermore, it was demonstrated that the cyclopenten-1,2-dione moiety of 4 nonenzymatically reacted with the catechin A-ring to yield the conjugate 5. Similar conjugations probably occur with procyanidins; thus, these reactions are possibly responsible for the decrease in the levels of 1 in leaves. The same cyclopenten-1,2-dione product 4 was also generated by treatment of 1 with a wood-rotting mushroom, Lentinula edodes, and further oxidative cleavage of a second pyrogallol ring of 4 was also observed. The results indicate the presence of a common degradation mechanism of 1 by plants and microbes.

6.
Eur Radiol Exp ; 4(1): 4, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993864

RESUMO

BACKGROUND: To reveal trends in bone microarchitectural parameters with increasing spatial resolution on ultra-high-resolution computed tomography (UHRCT) in vivo and to compare its performance with that of conventional-resolution CT (CRCT) and micro-CT ex vivo. METHODS: We retrospectively assessed 5 tiger vertebrae ex vivo and 16 human tibiae in vivo. Seven-pattern and four-pattern resolution imaging were performed on tiger vertebra using CRCT, UHRCT, and micro-CT, and on human tibiae using UHRCT. We measured six microarchitectural parameters: volumetric bone mineral density (vBMD), trabecular bone volume fraction (bone volume/total volume, BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and connectivity density (ConnD). Comparisons between different imaging resolutions were performed using Tukey or Dunnett T3 test. RESULTS: The vBMD, BV/TV, Tb.N, and ConnD parameters showed an increasing trend, while Tb.Sp showed a decreasing trend both ex vivo and in vivo. Ex vivo, UHRCT at the two highest resolutions (1024- and 2048-matrix imaging with 0.25-mm slice thickness) and CRCT showed significant differences (p ≤ 0.047) in vBMD (51.4 mg/cm3 and 63.5 mg/cm3 versus 20.8 mg/cm3), BV/TV (26.5% and 29.5% versus 13.8 %), Tb.N (1.3 l/mm and 1.48 l/mm versus 0.47 l/mm), and ConnD (0.52 l/mm3 and 0.74 l/mm3 versus 0.02 l/mm3, respectively). In vivo, the 512- and 1024-matrix imaging with 0.25-mm slice thickness showed significant differences in Tb.N (0.38 l/mm versus 0.67 l/mm, respectively) and ConnD (0.06 l/mm3 versus 0.22 l/mm3, respectively). CONCLUSIONS: We observed characteristic trends in microarchitectural parameters and demonstrated the potential utility of applying UHRCT for microarchitectural analysis.

7.
Intern Med ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31956202

RESUMO

An 88-year-old man was admitted for elevated liver enzyme levels. Nine years earlier, the patient had been diagnosed with diffuse large B-cell lymphoma (DLBCL) and undergone rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisone (R-CHOP) therapy. This patient previously had had a hepatitis B virus (HBV) infection before chemotherapy. After the chemotherapy, he was administered an LHRH agonist for prostate cancer. We diagnosed him with HBV reactivation because of positive serum HBV-DNA. HBV reactivation can occur a long time after chemotherapy, particularly if another treatment with immunity-altering drugs is added. In such cases, additional surveillance may be required to detect HBV reactivation.

8.
Hum Fertil (Camb) ; : 1-5, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31955637

RESUMO

Varicocele is a common cause of male infertility. It is reported that low sperm concentration, motility and morphology are indicative of increased sperm DNA fragmentation index (DFI) in men with varicocele. Although research has been conducted into the relationship between varicocele and DFI, little is known about seminal oxidation-reduction potential (ORP) in varicocele patients. We assessed the relationship between varicocele with seminal ORP and sperm DFI in both fertile and infertile men. This prospective case-control study compared the findings from infertile men with varicocele to those of men with normal spermatogenesis without varicocele. Semen samples were collected and assessed using the WHO (2010) guidelines. ORP was measured (mV) and normalized to sperm concentration (mV/106 sperm/mL). DFI was measured using the sperm chromatin structure assay (SCSA) method. For group comparisons, only samples with a concentration >1 × 106 sperm/mL were included. Infertile men with varicocele had significantly lower mean sperm concentration, motility and total sperm count. Conversely, infertile men with varicocele had a significantly higher mean serum FSH level, and higher ORP and DFI values than fertile controls. ORP was higher in patients with varicocele and positively correlated with DFI (p < 0.01). ORP and DFI showed significant negative correlations with semen parameters (sperm concentration, motility and total sperm count) in infertile men with a varicocele.

9.
AJR Am J Roentgenol ; 214(3): 605-612, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31913072

RESUMO

OBJECTIVE. This study evaluated the utility of a deep learning method for determining whether a small (≤ 4 cm) solid renal mass was benign or malignant on multiphase contrast-enhanced CT. MATERIALS AND METHODS. This retrospective study included 1807 image sets from 168 pathologically diagnosed small (≤ 4 cm) solid renal masses with four CT phases (unenhanced, corticomedullary, nephrogenic, and excretory) in 159 patients between 2012 and 2016. Masses were classified as malignant (n = 136) or benign (n = 32). The dataset was randomly divided into five subsets: four were used for augmentation and supervised training (48,832 images), and one was used for testing (281 images). The Inception-v3 architecture convolutional neural network (CNN) model was used. The AUC for malignancy and accuracy at optimal cutoff values of output data were evaluated in six different CNN models. Multivariate logistic regression analysis was also performed. RESULTS. Malignant and benign lesions showed no significant difference of size. The AUC value of corticomedullary phase was higher than that of other phases (corticomedullary vs excretory, p = 0.022). The highest accuracy (88%) was achieved in corticomedullary phase images. Multivariate analysis revealed that the CNN model of corticomedullary phase was a significant predictor for malignancy compared with other CNN models, age, sex, and lesion size. CONCLUSION. A deep learning method with a CNN allowed acceptable differentiation of small (≤ 4 cm) solid renal masses in dynamic CT images, especially in the corticomedullary image model.

10.
Int J Hematol ; 111(2): 267-277, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31713713

RESUMO

Little is known about the prognostic significance of muscle loss for allogeneic hematopoietic stem cell transplantation (allo-HCT). We retrospectively analyzed consecutive patients who received allo-HCT from 2013 to 2015. All patients underwent computed tomography (CT) imaging and bioelectrical impedance analysis (BIA) within 30 days before allo-HCT. Skeletal muscle area (cm2) at the third lumbar vertebra level on CT imaging and skeletal muscle mass (kg) measured by BIA were normalized by height in meters squared (m2) to calculate the skeletal muscle area index (SMI) and skeletal muscle mass index (SMMI). SMI and SMMI were significantly correlated (r = 0.744; P < 0.001). The cumulative incidence of 1-year non-relapse mortality (NRM) was significantly higher in patients with low SMI than high SMI (17% versus 0%, respectively; P = 0.023). Overall survival was shorter in patients with low SMI than high SMI (56% versus 93%, respectively; P < 0.001). In univariate analysis, low SMI was associated with increased risk of NRM (HR 7.46; 95% CI 1.05-52.98; P = 0.044), and in multivariate analysis it was associated with higher overall mortality (HR 5.35; 95% CI 1.71-16.72; P = 0.004). These results suggest that low muscle mass is an independent predictor of mortality after allo-HCT.

11.
Int J Hematol ; 111(1): 120-130, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31641956

RESUMO

How low-dose anti-thymocyte globulin (ATG) for prophylaxis of graft-versus-host disease (GVHD) influences immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HCT) remains incompletely understood. We prospectively enrolled 41 consecutive adult patients and conducted cytometry-based immunophenotyping for 12 months after allo-HCT. Rabbit ATG (Thymoglobulin) was administered at a median total dose of 1.75 mg/kg in 16 of the 41 patients. Compared with patients who did not receive ATG, those who did had a significantly smaller number of naïve T cells (especially CD4+ ) within three months after allo-HCT. No significant difference was observed between the two groups in the reconstitution of other T cells (effector, memory, Th1, Th2, Th17, Treg, and Tfh), B cells (transitional, naïve, memory, and plasmablast), NK cells (regulatory and cytolytic), or dendritic cells (myeloid and plasmacytoid). Patients with fewer CD4+ naïve T cells than the median count (7.60 cells/µL) at two months after allo-HCT developed chronic GVHD less frequently than those with CD4+ naïve T cells above the median count (2-year cumulative incidences were 0.31 and 0.53, respectively; p = 0.133). This pilot study suggests low-dose Thymoglobulin suppresses the recovery of naïve T cells after allo-HCT, which may contribute to a lower incidence of chronic GVHD.

12.
J Gastrointest Surg ; 24(2): 460-461, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31485906

RESUMO

BACKGROUND: Portal vein stenosis develops in 3.4-14% of split liver transplantation1-3 and its early detection and treatment are essential to achieve long-term graft survival,2-5 although the diagnostic capability of conventional modalities such as Doppler ultrasound and computed tomography is limited.1,4,5 METHODS: This study used computational fluid dynamics to analyze portal vein hemodynamics in the management of post-transplant portal vein stenosis. To perform computational fluid dynamics analyses, three-dimensional portal vein model was created using computed tomographic DICOM data. The inlet flow condition was set according the flow velocity measured on Doppler ultrasonography. Finally, portal vein flow was simulated on a fluid analysis software (Software Cradle, Japan). RESULTS: An 18-month-old girl underwent liver transplantation using a left lateral graft for biliary atresia. At the post-transplant 1-week evaluation, the computational fluid dynamics streamline analysis visualized vortices and an accelerated flow with a velocity ratio < 2 around the anastomotic site. The wall shear stress analysis revealed a high wall shear stress area within the post-anastomotic portal vein. At the post-transplant 6-month evaluation, the streamline analysis illustrated the increased vortices and worsening flow acceleration to reach the proposed diagnostic criteria (velocity ratio > 3:1).3,5 The pressure analysis revealed a positive pressure gradient of 3.8 mmHg across the stenotic site. Based on the findings, the patient underwent percutaneous transhepatic portal venoplasty with balloon dilation. The post-treatment analyses confirmed the improvement of a jet flow, vortices, a high wall shear stress, and a pressure gradient. DISCUSSION: The computational fluid dynamics analyses are useful for prediction, early detection, and follow-up of post-transplant portal vein stenosis and would be a promising technology in post-transplant management.

13.
Organogenesis ; 16(1): 1-13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31679437

RESUMO

In recent years, the demand for functional small-diameter (< 6 mm) artificial vascular grafts has greatly increased due to an increase in the number of patients with vascular heart disease. However, currently, there are no available commercial small-diameter grafts. The objective of this research was to develop a porous silk fibroin (SF)-coated poly(ethylene terephthalate) (PET) graft with a diameter < 6 mm. The graft was compared with a gelatin-coated PET graft because the latter PET graft with a diameter ~ 6 mm was widely used as a commercial vascular graft. Initially, porous SF was prepared using Glyc as the porogen [termed SF(Glyc)] and the PET grafts were prepared through the double-Raschel knitting method. Subsequently, the degradation of the SF coating was monitored using protease XIV in vitro and was compared with that observed in gelatin-coated PET grafts. Finally, these grafts were also implanted into rats for an in vivo comparison. In degradation experiments, after 7 days, the SF was clearly digested by protease XIV, but the gelatin on the graft was still remained at the outer surface. In implantation experiments in rats, the SF(Glyc)-coated PET graft was rapidly degraded in vivo and remodeling to self-tissues was promoted compared with the gelatin-coated PET graft. Thrombus formation and intimal hyperplasia were observed in the gelatin-coated PET graft; however, such side reactions were not observed in the SF(Glyc)-coated PET graft. Thus, the porous SF(Glyc)-coated PET graft with a small diameter < 6 mm may be useful as a commercial vascular graft.

14.
Biotechnol Rep (Amst) ; 24: e00401, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788440

RESUMO

In this study, we have developed a novel method to monitor transgene expression in tissues by blood sampling. We administered plasmid DNA (pDNA) encoding non-secretory form of firefly luciferase as a reporter gene and pDNA encoding secretable Gaussia princeps luciferase as a monitor gene simultaneously into mice. Good positive correlations were found between log-transgene expression of the reporter gene and the monitor gene in the treated muscle, between the monitor gene in the treated muscle and plasma, and consequently between the reporter gene in the treated muscle and the monitor gene in plasma after naked pDNA transfer into the muscle of mice. Such positive correlations were also found with gastric serosal surface instillation of naked pDNA, intravenous injection of lipoplex, and hydrodynamics-based injection of naked pDNA. We developed monitoring method of transgene expression in tissues by blood sampling, which was named 'Therapeutic transgene monitoring (TTM)', after 'Therapeutic drug monitoring (TDM)'.

15.
Opt Express ; 27(21): 30875-30892, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684330

RESUMO

In externally seeded free-electron lasers (FELs) that rely on a frequency upconversion scheme to generate intense short-wavelength light pulses, the slippage effect in the radiator imposes a lower limit on the FEL pulse duration, which is typically on the order of a few tens of femtoseconds. Recently it was proposed that a combination of a chirped microbunch and a tapered undulator can be used to break this limit. Although the method has the potential to reduce the FEL pulse duration down to a level that cannot be achieved by current state-of-the-art technology, it requires a very short seed pulse (∼ one optical cycle or less), making it challenging to put this concept into practical use. Here, we propose an alternative technique to relax the requirement on the seed pulse length. We show that the modified scheme allows generation of FEL pulses with durations much shorter than that determined by the seed pulse and the slippage effect. The performance of the method, which can easily be implemented at existing seeded FEL user facilities, is evaluated through a campaign of analytical calculations and simulations. For our set of typical seeded FEL parameters, we expect the generation of 1.6 fs long pulses at 26 nm with a peak power of 10 GW using a 20 fs long chirped seed pulse operating at 260 nm.

16.
Molecules ; 24(23)2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31771266

RESUMO

The leaves of Castanopsis sieboldii (Fagaceae) contain characteristic hexahydroxydiphenoyl (HHDP) esters of 28-O-glucosyl 2α,3ß,23,24-tetrahydroxyolean- and urs-12-en-28-oic acids. In this study, uncharacterized substances were detected in the young leaves, which are not observed in the mature leaves. Preliminary HPLC analyses indicated that the substances had dehydro-HHDP (DHHDP) ester groups; however, the esters were unstable and decomposed during extraction. Therefore, the compounds were isolated as their stable phenazine derivatives by extracting the young leaves with acidic aqueous EtOH containing o-phenylenediamine. The structures of the phenazine derivatives indicated that the unstable metabolites of the young leaves were 3,24-DHHDP esters of the abovementioned triterpenes. Extraction of the young leaves with 80% acetonitrile containing reducing agents, ascorbic acid or dithiothreitol afforded the corresponding HHDP esters. Furthermore, heating of the young leaves in 80% acetonitrile also yielded the same HHDP esters as the reduction products. The results suggested that the HHDP esters are reductively produced from DHHDP esters in the young leaves. In addition, the structures of five previously reported triterpene HHDP esters were revised.

17.
Xenobiotica ; : 1-9, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31631733

RESUMO

1. The expression and activity of drug-metabolizing enzymes are known to affect the pharmacokinetics of drugs metabolized in the liver. Here, we assessed the effect of acetaminophen (APAP)-induced hepatotoxicity on the mRNA expression of drug-metabolizing enzymes and elucidated the underlying mechanism using three-dimensional (3D) cultures of HepG2 cells.2. 3D culture cells enabled us to establish an in vitro model of APAP-induced hepatotoxicity which showed the increase in N-acetyl-p-benzoquinone imine production, reactive oxygen species (ROS) generation and cellular injury.3. In this 3D culture model, APAP treatment significantly increased the mRNA expression of drug-metabolizing enzymes (cytochrome P450 [CYP]3A4, CYP2E1 and UDP-glucuronosyltransferase 1A6) and their nuclear receptors (pregnane X receptor and constitutive androstane receptor) compared with untreated cells. Treatment with N-acetylcysteine, a therapeutic agent for APAP-induced hepatotoxicity, suppressed these increases. In addition, the mRNA expression of drug-metabolizing enzymes and nuclear receptors were elevated depending on the concentration of H2O2, one of ROS involved in the development of APAP-induced hepatotoxicity. The mRNA expression of nuclear receptors increased before that of drug-metabolizing enzymes.4. In conclusion, ROS may induce the mRNA expression of nuclear receptors and promote the transcription of drug-metabolizing enzymes in the in vitro model of APAP-induced hepatotoxicity.

18.
Blood Adv ; 3(18): 2764-2777, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551243

RESUMO

Although differences in the incidence of chronic graft-versus-host disease (GVHD) across the races have been suggested, these have not been systematically investigated. This study compared the incidence, sites, severity, and outcomes of late acute GVHD and chronic GVHD according to National Institutes of Health (NIH) consensus criteria between Japanese (n = 413) and white (n = 708) patients after first allogeneic hematopoietic cell transplantation. Analysis was stratified according to bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). Japanese patients, compared with white patients, had a similar incidence of late acute GVHD (BMT, 19% vs 16%; PBSCT, 19% vs 16%) but experienced more frequent liver late acute GVHD as defined by transaminase elevation (BMT, 79% vs 8%; PBSCT, 92% vs 33%) and less frequent gastrointestinal late acute GVHD (BMT, 11% vs 58%; PBSCT, 20% vs 68%). Japanese patients were more likely to discontinue systemic immunosuppression after late acute GVHD than white patients (hazard ratio, 3.68; 95% confidence interval, 1.96-6.94; P < .001). Japanese patients, compared with white patients, had a lower incidence of chronic GVHD (BMT, 15% vs 30% [P = .002]; PBSCT, 37% vs 45% [P < .001]) and experienced more frequent chronic GVHD of the mouth, eyes, and liver and less frequent gastrointestinal chronic GVHD. The duration of immunosuppressive treatment of NIH chronic GVHD was similar between the races. These differences could not be entirely attributed to practice variation between the centers. This study shows that the incidence, affected sites, severity, and clinical outcomes of late acute GVHD and NIH chronic GVHD differ between Japanese and white patients.

19.
Eur J Haematol ; 103(6): 578-587, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31487403

RESUMO

OBJECTIVE: CD204+ tumor-associated macrophages are associated with adverse outcomes of various malignancies. We performed a study to elucidate the role of CD204+ macrophages in allogeneic hematopoietic cell transplantation (allogeneic HCT). METHODS: In a total of 81 patients who received allogeneic HCT for non-remission malignant lymphoma, immunohistochemical staining of CD204 using specimens preserved before allogeneic HCT was performed. According to the average number of CD204+ macrophages in a high-power field, patients were categorized into three groups: low (<25th percentile), intermediate (≥25th percentile and <50th percentile), and high (≥50th percentile). RESULTS: The B-cell lymphoma proportion was higher in the low group, while T-cell lymphoma and adult T-cell leukemia proportions were higher in the high group. The 3-year overall survival (OS) was poorest in the high group; low vs intermediate vs high = 83.3% vs 43.7% vs 20.2% (P < .01). The 3-year cumulative incidences of relapse were significantly higher in the high group than the intermediate and low groups: 67.0% vs 38.1% vs 18.2% (P < .01). In multivariate analyses, the numbers of CD204+ macrophages were independent risk factors of poorer OS and cumulative incidences of relapse. CONCLUSIONS: CD204+ macrophages might be associated with poorer prognosis in allogeneic HCT for malignant lymphomas.

20.
Circ J ; 83(10): 2049-2060, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31391387

RESUMO

BACKGROUND: Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.Methods and Results:Patients with NYHA functional class II-IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40-1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760). CONCLUSIONS: The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.

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