A myocardial bridge (MB), partially covering the coronary artery, is a congenital anatomical variant usually present in the left anterior descending coronary artery (LAD). MB causes coronary heart ...disease (CHD) by 2 distinct mechanisms influenced by the anatomical properties of the MB, such as its length, thickness, and location. One is direct MB compression of the LAD at cardiac systole, resulting in delayed arterial relaxation at diastole, reduced blood flow reserve, and decreased blood perfusion. The other is enhancement of coronary atherosclerosis causing stenosis of the LAD proximal to the MB, occurring because of endothelial injury arising from the abnormal hemodynamics provoked by retrograde blood flow up toward the left coronary ostium at cardiac systole. The magnitude of the effect of the 2 distinct mechanisms of the MB on LAD blood flow is prescribed by a common root of the MB-muscle mass volume generated by those properties. Furthermore, the anatomical properties of the MB are closely associated with the choice of treatment and therapeutic outcome in CHD patients having an MB. Thus, the anatomical properties of an MB should be considered in the diagnosis and management of CHD patients with this anomaly. (Circ J 2011; 75: 1559-1566)
Intravascular large B‐cell lymphoma (IVLBCL) is a rare disease entity with a high incidence of central nervous system (CNS) involvement at diagnosis. To evaluate CNS involvement, particularly ...recurrence including progression on therapy and relapse of IVLBCL, we retrospectively analyzed 109 patients with IVLBCL receiving chemotherapies with or without rituximab. In 82 patients (75%) without CNS involvement at initial diagnosis, risk of CNS recurrence at 3 years was 25% with a median follow‐up in survivors of 39 months (range, 2–158 months). In 27 patients (25%) with CNS involvement at initial diagnosis, risk of CNS recurrence at 1 year was 25% with a median follow‐up in survivors of 18 months (range, 10–77 months). Duration from diagnosis to CNS recurrence tended to be short in patients with CNS involvement at diagnosis. No significant difference in risk of CNS recurrence was found between patients receiving chemotherapies with or without rituximab. On multivariate analysis skin involvement at initial diagnosis was identified as a predictive factor for CNS recurrence in patients without CNS involvement at diagnosis (hazard ratio, 5.27; 95% confidence interval, 1.59–17.4; P = 0.007). Survival rate after CNS recurrence at 2 years was 12% in patients without CNS involvement at diagnosis. Central nervous system recurrence is a serious complication in IVLBCL patients and optimal strategies for CNS involvement should be established to obtain further improvements to clinical outcomes in the rituximab era. (Cancer Sci 2010)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Low-dose aspirin is widely used for the prevention of cardiovascular events. The prevalence of gastroduodenal injuries and the risk factor profile including gastroprotective drug therapy ...needs to be clarified in Japanese patients taking daily aspirin for cardioprotection.
Methods
This Management of Aspirin-induced Gastro-Intestinal Complications (MAGIC) study was conducted with a prospective nationwide, multicenter, real-world registry of Japanese patients at high-risk of cardiovascular diseases who were taking regular aspirin (75–325 mg) for 1 month or more. All patients underwent endoscopic examination for detection of gastroduodenal ulcer and mucosal erosion. The risk factor profiles including the concurrent drug therapy were compared for those patients with gastroduodenal problems and those without.
Results
Gastroduodenal ulcer and erosion were detected in 6.5, and 29.2 % of the 1,454 patients receiving aspirin, respectively.
H. pylori
infection was associated with an increased risk for ulcer: OR 1.83 (1.18–2.88
p
= 0.0082). Risk of erosion was lower with enteric-coated aspirin than with buffered aspirin: odds ratio (OR) 0.47 (0.32–0.70,
p
= 0.0002). Patients receiving proton pump inhibitors had lower risks for both gastroduodenal ulcer and erosion: OR 0.34 (0.15–0.68,
p
= 0.0050) and 0.32 (0.22–0.46,
p
< 0.0001), respectively. However, those receiving histamine 2-receptor antagonists had reduced risks for erosion but not for ulcer: OR 0.49 (0.36–0.68,
p
< 0.0001).
Conclusion
Gastroduodenal ulcer and erosion are common in Japanese patients taking low dose aspirin for cardioprotection. Proton pump inhibitors reduce the risk of gastroduodenal mucosal injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Axicabtagene ciloleucel (axi-cel) is an autologous chimeric antigen receptor T-cell based anti-CD19 therapy. The ZUMA-1 study, multicenter, single-arm, registrational Phase 1/2 study of ...axi-cel demonstrated high objective response rate in patients with relapsed/refractory large B-cell lymphoma. Here, we present the results of the bridging study to evaluate the efficacy and safety of axi-cel in Japanese patients (JapicCTI-183914).
Methods
This study was the phase 2, multicenter, open-label, single-arm trial. Following leukapheresis, axi-cel manufacturing and lymphodepleting chemotherapy, patients received a single infusion of axi-cel (2.0 × 10
6
cells/kg). Bridging therapy between leukapheresis and conditioning chemotherapy was not allowed. The primary endpoint was objective response rate.
Results
Among 17 enrolled patients, 16 received axi-cel infusion. In the 15 efficacy evaluable patients, objective response rate was 86.7% (95% confidence interval: 59.5–98.3%); complete response/partial response were observed in 4 (26.7%)/9 (60.0%) patients, respectively. No dose-limiting toxicities were observed. Grade ≥ 3 treatment-emergent adverse events occurred in 16 (100%) patients—most commonly neutropenia (81.3%), lymphopenia (81.3%) and thrombocytopenia (62.5%). Cytokine release syndrome occurred in 13 (81.3%) patients (12 cases of grade 1 or 2 and 1 case of grade 4). No neurologic events occurred. Two patients died due to disease progression, but no treatment-related death was observed by the data-cutoff date (October 23, 2019).
Conclusion
The efficacy and safety of axi-cel was confirmed in Japanese patients with relapsed/refractory large B-cell lymphoma who have otherwise limited treatment options.
Trial registration
JapicCTI-183914.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) −/+ rituximab (R) is the standard chemotherapeutic regimen for aggressive lymphoma, but is insufficient for aggressive lymphoma ...with adverse prognostic factors. Dose-adjusted (DA)-EPOCH (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisolone) −/+ R demonstrates excellent efficacy against some aggressive lymphoma. Thus, we conducted a retrospective study to evaluate the feasibility and efficacy of this therapy in clinical practice. We enrolled 149 patients from 17 institutions diagnosed between 2007 and 2015. The median follow-up period for survivors was 27 months (range 0.2–123). The complete response (CR) rate of newly diagnosed patients was 79% (95% CI 68–87%). All patients were hospitalized to receive this therapy and 94% of patients also received granulocyte-colony-stimulating factor support. There were no treatment-related deaths. Febrile neutropenia (FN) and grade 3 or 4 infection occurred in 55% and 28% of patients, respectively. There were no significant differences in FN or infection between young (≤ 65 years) and elderly patients (> 65 years). In newly diagnosed diffuse large B-cell lymphoma-not otherwise specified patients (
n
= 46), the CR rate was 80% (95% CI 64–91%) and the 2-year OS rate was 81% (95% CI 66–90%). In the present study, DA-EPOCH −/+ R exhibited excellent efficacy and feasibility for aggressive lymphoma.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We found a variational case relating to the arteries distributed to the liver and pancreas during the routine cadaver dissection course. The common hepatic artery originated from the superior ...mesenteric artery as the first branch. The common hepatic artery was soon divided into the left and right hepatic arteries and distributed to the left and right lobe of the liver. The superior pancreaticoduodenal artery arose from the gastroduodenal artery, a branch of the left hepatic artery. The inferior pancreaticoduodenal artery originated from the superior mesenteric artery. Besides, two posterior branches of the right hepatic artery supplied the duodenum and the head of the pancreas. The arterial arcades were formed behind the head of the pancreas among the superior pancreaticoduodenal artery and these two posterior branches of the right hepatic artery. In conclusion, this case can be considered a rare case in which the replaced common hepatic artery and replaced right hepatic artery occurred simultaneously. The coexisting of these two replaced arteries suggests that the developmental processes to form these variations are independent.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nanoparticles (NPs) enhance soybean growth; however, their precise mechanism is not clearly understood. To develop a more effective method using NPs for the enhancement of soybean growth, fiber ...crosslinked with zinc oxide (ZnO) NPs was prepared. The solution of ZnO NPs with 200 nm promoted soybean growth at the concentration of 10 ppm, while fibers crosslinked with ZnO NPs promoted growth at a 1 ppm concentration. Soybeans grown on fiber cross-linked with ZnO NPs had higher Zn content in their roots than those grown in ZnO NPs solution. To study the positive mechanism of fiber crosslinked with ZnO NPs on soybean growth, a proteomic technique was used. Proteins categorized in photosynthesis and secondary metabolism accumulated more in soybeans grown on fiber crosslinked with ZnO NPs than in those grown in ZnO NPs solution. Furthermore, significantly accumulated proteins, which were NADPH oxidoreductase and tubulins, were confirmed using immunoblot analysis. The abundance of NADPH oxidoreductase increased in soybean by ZnO NPs application. These results suggest that fiber crosslinked with ZnO NPs enhances soybean growth through the increase of photosynthesis and secondary metabolism. Additionally, the accumulation of NADPH oxidoreductase might relate to the effect of auxin with fiber crosslinked with ZnO NPs on soybean growth.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
On the basis of immunohistochemistry, diffuse large B-cell lymphoma (DLBCL) is categorized as a germinal center B-cell (GCB) or non-GCB subtype. Recent integrated genomic analyses have highlighted ...the importance of the JAK-STAT3 pathway in the molecular pathogenesis of DLBCL. However, its relevance to clinical outcomes remains controversial. Therefore, we evaluated the extent of the nuclear expression of phosphorylated STAT3 (pSTAT3), a surrogate marker of signal transducer and activator of transcription 3 (STAT3) activation, by immunohistochemistry. We also analyzed the potential relationship between pSTAT3 positivity (defined as ≥40% positive neoplastic cells) and clinicopathologic characteristics in 294 patients with DLBCL. pSTAT3 was detected in 122 patients (42%), with a higher rate in the non-GCB subtype than in the GCB subtype (57% vs. 28%, P<0.001). Factors potentially activating STAT3, MYD88L265P, and Epstein-Barr virus-encoded small RNA were identified in the pSTAT3-positive non-GCB subtype, whereas the pSTAT3-positive GCB subtype often showed STAT3 mutations and lacked EZH2 mutations and the rearrangements of BCL2 and MYC. Multivariate analyses revealed that the pSTAT3-positive GCB subtype showed a favorable prognosis (HR: 0.17; 95% confidence interval, 0.04-0.7; P=0.014). These findings suggest that pSTAT3 positivity may have a unique impact on the clinicopathologic characteristics of DLBCL, making it a promising novel marker for the favorable prognosis of patients with the GCB subtype.
Genetic alterations in myelodysplastic syndromes (MDS) are critical for pathogenesis. We previously showed that peripheral blood cell‐free DNA (PBcfDNA) may be more sensitive for genetic/epigenetic ...analyses than whole bone marrow (BM) cells and mononuclear cells in peripheral blood (PB). Here we analyzed the detailed features of PBcfDNA and its utility in genetic analyses in MDS. The plasma‐PBcfDNA concentration in MDS and related diseases (N = 33) was significantly higher than that in healthy donors (N = 14; P = 0.041) and in International Prognostic Scoring System higher‐risk groups than that in lower‐risk groups (P = 0.034). The concentration of plasma‐/serum‐PBcfDNA was significantly correlated with the serum lactate dehydrogenase level (both P < 0.0001) and the blast cell count in PB (P = 0.034 and 0.025, respectively). One nanogram of PBcfDNA was sufficient for one assay of Sanger sequencing using optimized primer sets to amplify approximately 160‐bp PCR products. PBcfDNA (approximately 50 ng) can also be utilized for targeted sequencing. Almost all mutations detected in BM‐DNA were also detected using corresponding PBcfDNA. Analyses using serially harvested PBcfDNA from an RAEB‐2 patient showed that the somatic mutations and a single nucleotide polymorphism that were detected before allogeneic transplantation were undetectable after transplantation, indicating that PBcfDNA likely comes from MDS clones that reflect the disease status. PBcfDNA may be a safer and easier alternative to obtain tumor DNA in MDS.
PBcfDNA concentration is significantly higher in IPSS higher risk MDS patients than that in lower risk patients. PBcfDNA can be a safer and easier alternative tumor DNA source in MDS for mutation analyses using not only conventional Sanger sequence strategy but also next generation targeted sequencing strategy.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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