The effects of incorporated poly(
d-lactic acid) (PDLA) as poly(lactic acid) (PLA) stereocomplex crystallites on the isothermal and non-isothermal crystallization behavior of poly(
l-lactic acid) ...(PLLA) from the melt were investigated for a wide PDLA contents from 0.1 to 10
wt%. In isothermal crystallization from the melt, the radius growth rate of PLLA spherulites (crystallization temperature (
T
c)≥125
°C), the induction period for PLLA spherulite formation (
t
i) (
T
c≥125
°C), the growth mechanism of PLLA crystallites (90
°C≤
T
c≤150
°C), and the mechanical properties of the PLLA films were not affected by the incorporation of PDLA or the presence of stereocomplex crystallites as a nucleating agent. In contrast, the presence of stereocomplex crystallites significantly increased the number of PLLA spherulites per unit area or volume. In isothermal crystallization from the melt, at PDLA content of 10
wt%, the starting, half, and ending times for overall PLLA crystallization (
t
c(S),
t
c(1/2), and
t
c(E), respectively) were much shorter than those at PDLA content of 0
wt%, due to the increased number of PLLA spherulites. Reversely, at PDLA content of 0.1
wt%, the
t
c(S),
t
c(1/2), and
t
c(E) were longer than or similar to those at PDLA content of 0
wt%, probably due to the long
t
i and the decreased number of spherulites. This seems to have been caused by free PDLA chains, which did not form stereocomplex crystallites. On the other hand, at PDLA contents of 0.3–3
wt%, the
t
c(S),
t
c(1/2), and
t
c(E) were shorter than or similar to those at PDLA content of 0
wt% for the
T
c range below 95
°C and above 125
°C, whereas this inclination was reversed for the
T
c range of 100–120
°C. In the non-isothermal crystallization of as-cast or amorphous-made PLLA films during cooling from the melt, the addition of PDLA above 1
wt% was effective to accelerate overall PLLA crystallization. The X-ray diffractometry could trace the formation of stereocomplex crystallites in the melt-quenched PLLA films at PDLA contents above 1
wt%. This study revealed that the addition of small amounts of PDLA is effective to accelerate overall PLLA crystallization when the PDLA content and crystallization conditions are scrupulously selected.
OBJECTIVE Aging of the population may lead to epidemiological changes with respect to chronic subdural hematoma (CSDH). The objectives of this study were to elucidate the current epidemiology and ...changing trends of CSDH in Japan. The authors analyzed patient information based on reports using a Japanese administrative database associated with the diagnosis procedure combination (DPC) system. METHODS This study included patients with newly diagnosed CSDH who were treated in hospitals participating in the DPC system. The authors collected data from the administrative database on the following clinical and demographic characteristics: patient age, sex, and level of consciousness on admission; treatment procedure; and outcome at discharge. RESULTS A total of 63,358 patients with newly diagnosed CSDH and treated in 1750 DPC participation hospitals were included in this study. Analysis according to patient age showed that the most common age range for these patients was the 9th decade of life (in their 80s). More than half of patients 70 years old or older presented with some kind of disturbance of consciousness. Functional outcomes at discharge were good in 71.6% (modified Rankin Scale mRS score 0-2) of cases and poor in 28.4% (mRS score 3-6). The percentage of poor outcomes tended to be higher in elderly patients. Approximately 40% of patients 90 years old or older could not be discharged to home. The overall recurrence rate for CSDH was 13.1%. CONCLUSIONS This study shows a chronological change in the age distribution of CSDH among Japanese patients, which may be affecting the prognosis of this condition. In the aging population of contemporary Japan, patients in their 80s were affected more often than patients in other age categories, and approximately 30% of patients with CSDH required some help at discharge. CSDH thus may no longer have as good a prognosis as had been thought.
Background & Aims Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single ...nucleotide polymorphisms in ADH1B and ALDH2 , which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. Methods We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2 . Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. Results A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5′ thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6 ) factors. Many tumors contained mutations in genes that regulate the cell cycle ( TP53, CCND1, CDKN2A , FBXW7 ); epigenetic processes ( MLL2, EP300, CREBBP , TET2 ); and the NOTCH ( NOTCH1 , NOTCH3 ), WNT ( FAT1 , YAP1 , AJUBA ) and receptor-tyrosine kinase−phosphoinositide 3-kinase signaling pathways ( PIK3CA , EGFR , ERBB2 ). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. Conclusions We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.
Over the last 60 years, many reports have investigated carotid endarterectomy (CEA) and techniques have thus changed and improved. In this paper, we review the recent literature regarding operational ...maneuvers for CEA and discuss future problems for CEA. Longitudinal skin incision is common, but the transverse incision has been reported to offer minimal invasiveness and better cosmetic effects for CEA. Most surgeons currently use microscopy for dissection of the artery and plaque. Although no monitoring technique during CEA has been proven superior, multiple monitors offer better sensitivity for predicting postoperative neurological deficit. To date, data are lacking regarding whether routine shunt or selective shunt is better. Individual surgeons thus need to select the method with which they are more comfortable. Many surgical techniques have been reported to obtain distal control of the internal carotid artery in patients with high cervical carotid bifurcation or high plaque, and minimally invasive techniques should be considered. Multiple studies have shown that patch angioplasty reduces the risks of stroke and restenosis compared with primary closure, but few surgeons in Japan have been performing patch angioplasty. Most surgeons thus experience only a small volume of CEAs in Japan, so training programs and development of in vivo training models are important.
Adipose-derived stem cell (AdSC) has been attracting attention as a convenient stem cell source. Not only AdSC can differentiate into various tissue cells, but it can also accelerate cell ...proliferation, anti-inflammation, and angiogenesis by secreting paracrine factors. Studies have demonstrated AdSC treatment of ischemic heart. However, an improvement in the remaining live AdSCs administered at the injected site while maintaining paracrine factor secretion is desired to achieve effective regenerative medicine. We previously reported the ABA-type tri-block copolymer of poly(ɛ-caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG), exhibiting temperature-responsive sol-to-gel transition as biodegradable injectable polymer (IP) systems. Moreover, we recently reported that the biodegradable temperature-triggered chemically cross-linked gelation systems exhibited longer gel state durations using tri-PCG attaching acryloyl groups and a polythiol derivative. In this study, we explored this IP-mediated AdSC delivery system. We investigated the cell viability, mRNA expression, and cytokine secretion of AdSCs cultured in the physical or chemical IP hydrogels. Both of these IP hydrogels retained a certain number of viable cells, and RT-PCR and ELISA analyses revealed that mRNA expression and secretion of vascular endothelial growth factor of the AdSCs cultured in the chemical hydrogel were higher than the physical hydrogel. Moreover, AdSCs injected with the chemical hydrogel into ischemic heart model mice showed longer retention of the cells at the injected site and recovery from the ischemic condition. The results mean that the IP system is a promising candidate for a stem cell delivery system that exhibits the recovery of cardiac function for myocardial infarction treatment.
The morphology of the internal carotid artery (ICA) bifurcation is increasingly being recognized as the cause of atherosclerosis and vulnerable plaque leading to cerebral infarction. In this study, ...we investigated the relationship between carotid bifurcation angle and carotid plaque volume evaluated using black blood magnetic resonance imaging (BB-MRI). Among the 90 patients who underwent revascularization for atherosclerotic symptomatic carotid stenosis between April 2016 and October 2022 using BB-MRI, carotid plaque was evaluated in 57 patients. Relative overall signal intensity (roSI) was defined as the signal intensity of the plaque on T1-weighted images relative to the signal intensity of the sternocleidomastoid muscle in the same slice as the common carotid bifurcation. Regions showing roSI ≥ 1.0 were defined as plaque, and the plaque volume and relative plaque volume were measured from roSI ≥1.0 to ≥2.0 in 0.1 increments. We calculated the angles between the common carotid artery (CCA) and the ICA and between the CCA and the external carotid artery (ECA) on magnetic resonance angiography. We classified two groups according to carotid bifurcation angles based on the ICA angle: Group A = <35° and Group B = ≥35°. Compared with Group A (n = 42), Group B (n = 15) showed a greater relative plaque volume between roSI ≥ 1.3 and roSI ≥ 1.5. A significant correlation was identified between relative plaque volume with roSI ≥ 1.4 and ICA angle (p = 0.049). Vulnerable plaque was significantly more frequent in the group with an ICA angle of ≥35. Moreover, the ICA angle was significantly greater in patients with a roSI of ≥1.4.
Background
The global, randomized, phase 3 REACH-2 study (ClinicalTrials.gov identifier: NCT02435433) found significantly longer overall survival (OS) for second-line ramucirumab versus placebo ...(hazard ratio HR: 0.710, 95% confidence interval CI 0.531–0.949,
P
= 0.0199) in patients with advanced hepatocellular carcinoma (HCC) and alpha-fetoprotein (AFP) ≥ 400 ng/mL. This prespecified subgroup analysis evaluated the efficacy and safety of ramucirumab in the Japanese patients enrolled in the study.
Methods
Patients with advanced HCC and AFP ≥ 400 ng/mL after first-line sorafenib were randomized 2:1 to ramucirumab (8 mg/kg intravenously) or placebo every 2 weeks. Hazard ratios for progression-free survival (PFS) and OS (primary endpoint of the overall study) were estimated using the stratified Cox regression model. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with AFP ≥ 400 ng/mL.
Results
In the Japanese REACH-2 subpopulation, there were improvements for ramucirumab (
n
= 41) versus placebo (
n
= 18) in PFS (HR 0.282, 95% CI 0.144–0.553) and OS was numerically prolonged (HR 0.599, 95% CI 0.303–1.187), consistent with the significant benefit seen in the overall REACH-2 study population. In the ramucirumab and placebo arms, respectively, the objective response rate was 7.3% and 0%, and the disease control rate was 70.7% and 33.3%. The most frequently reported grade ≥ 3 treatment-emergent adverse event was hypertension (ramucirumab: 15%; placebo: 11%).
Conclusions
Ramucirumab after prior sorafenib improved PFS and OS compared with placebo, with a manageable safety profile, in the Japanese REACH-2 subpopulation, consistent with the overall REACH-2 study results. Ramucirumab is the first agent to demonstrate clinical benefit for Japanese patients with HCC in the second-line setting.
Endoscopic surgery was performed for acute or subacute subdural hematoma (SDH), and its effectiveness and safety in elderly patients were evaluated.
Between September 2007 and November 2013, ...endoscopic surgery was performed in 11 elderly patients with acute SDH (8 patients) and subacute SDH (3 patients). The criteria for surgery were as follows: 1) the presence of clinical symptoms; 2) age older than 70 years; 3) no brain injury (intracerebral hematoma, brain contusion); 4) absence of an enlarging SDH; and 5) no high risk of bleeding. Hematoma evacuation was performed with a 4-mm rigid endoscope with a 0° lens and a malleable irrigation suction cannula.
Endoscopic surgery was performed under local anesthesia. The mean age of the patients was 82.6 years (range 73-91 years). There were 5 female and 6 male patients. The mean preoperative Glasgow Coma Scale score was 12, and 5 patients had been receiving antithrombotic drug therapy. The mean operation time was 85 minutes. Only 1 patient had rebleeding, and reoperation with the same technique was performed uneventfully in this individual. A total of 7 patients had a good recovery (modified Rankin Scale Score 0-2) at discharge.
Endoscopic hematoma evacuation of acute and subacute SDH is a safe and effective method of clot removal that minimizes operative complications. This technique may be a less invasive method for treating elderly patients with acute and subacute SDHs.
The development of cancer is driven not only by genetic mutations but also by epigenetic alterations. Here, we show that TET1-mediated production of 5-hydroxymethylcytosine (5hmC) is required for the ...tumorigenicity of glioblastoma cells. Furthermore, we demonstrate that chromatin target of PRMT1 (CHTOP) binds to 5hmC. We found that CHTOP is associated with an arginine methyltransferase complex, termed the methylosome, and that this promotes the PRMT1-mediated methylation of arginine 3 of histone H4 (H4R3) in genes involved in glioblastomagenesis, including EGFR, AKT3, CDK6, CCND2, and BRAF. Moreover, we found that CHTOP and PRMT1 are essential for the expression of these genes and that CHTOP is required for the tumorigenicity of glioblastoma cells. These results suggest that 5hmC plays a critical role in glioblastomagenesis by recruiting the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of cancer-related genes.
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