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Objective: Although reports of endovascular treatment for intracranial arterial stenosis have been increasing recently, their efficacy remains to be elucidated. This study aimed to investigate the changes in cerebral hemodynamics of severe middle cerebral artery (MCA) stenosis patients by performing CT perfusion (CTP) after endovascular treatment., Methods: Subjects were those who underwent balloon angioplasty and stenting for symptomatic MCA M1 stenosis refractory to medical therapy at our hospital between 2008 and 2022. We included 36 patients (mean age 63.69 ± 15.24 years, 20 males) who underwent CTP before and within three weeks after treatment. The CTP parameters such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) were calculated as ipsilateral values divided by contralateral value., Results: Endovascular treatment consisted of 26 balloon angioplasty and 10 stenting procedures performed at an average of 1 month from onset. CTP was performed at an average of 5.5 days postoperatively. The mean overall stenosis rate decreased from 79.0% to 30.3%. In the balloon angioplasty group, it decreased from 77.6% to 35.3%, and in the stent group, it decreased from 82.7% to 17.5%. After treatment, rCBF and rMTT measured by CTP improved significantly (both p  < 0.001), whereas there was no significant change in rCBV. The improvement rates of rCBF and rMTT were mild higher in the stent group, but not significantly so., Conclusion: Balloon angioplasty and stenting for symptomatic MCA improved cerebral hemodynamics, resulting in significantly increased rCBF and decreased rMTT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Distinguishing human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy from hereditary spastic paraplegia in patients infected with HTLV-1 is challenging due to overlapping clinical symptoms. The aim of this study was to explore the possibility that hereditary spastic paraplegia is inherently present in patients diagnosed with HTLV-1-associated myelopathy., Methods: We performed whole-genome sequencing on 315 unrelated patients registered in the HTLV-1-Associated Myelopathy patient registry "HAM-net," from 2013 to 2022 in Japan. CSF inflammatory biomarkers, including CXCL10, were measured., Results: We identified 5 patients with pathogenic variants in the genes RTN2 , SPAST , VCP , and UBAP1 , which are the known causes of hereditary spastic paraplegia. These patients had no family history of hereditary spastic paraplegia. The levels of CSF inflammatory biomarkers were lower than expected in these patients, compared with disease severity., Discussion: Genetic analysis is useful for the differentiation of hereditary spastic paraplegia patients from HTLV-1-associated myelopathy patients, especially for the patients with low levels of CSF inflammatory markers. Here we report the presence of hereditary spinal cord diseases in patients diagnosed with HTLV-1-associated myelopathy and provides evidence that genetic analysis would be helpful in the diagnostic workflow., Competing Interests: The authors report no relevant disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Pseudomyxoma peritonei(PMP)is a rare condition caused by intraductal papillary mucinous neoplasm(IPMN). At our institution, 3 cases, along with literature review, of PMP caused by IPMN were treated with cytoreductive surgery. In case 1, a 70-year-old man was pathologically diagnosed with low-grade PMP with intraductal papillary mucinous carcinoma. Recurrence was discovered 68 months after surgery, and the patient died after 78 months. In case 2, a 69-year-old man was pathologically diagnosed with high-grade PMP with signet-ring cell carcinoma caused by intraductal papillary mucinous carcinoma. The patient died 8 months post-surgery. In case 3, a 77-year-old woman was pathologically diagnosed with low- grade(partially high-grade)PMP with intraductal papillary mucinous adenoma. There was a recurrence 14 months post- surgery. The patient is still alive because of systemic chemotherapy 32 months after surgery.

The escalating demand for meat, driven by global population growth, necessitates sustainable solutions for animal feed production. This study investigated the effects of substituting conventional protein resources in sow and piglet dietary regimens with black soldier fly (BSF; Hermetia illucens ) meal on reproductive efficiency, blood profile, piglet growth, and intestinal tissue morphology. The results indicate that substituting animal-derived and soy proteins with BSF meal does not compromise sow reproductive performance. Although no notable disparities were observed in piglet growth, the feed conversion ratio from the 28- to 35-day age marks were lower in the BSF-fed groups. This suggests that the animal protein-BSF substitution rate may require optimization, potentially involving chitin removal from BSF meal to enhance digestibility. Minor variations in the hematological composition and properties in piglets, with elevated high-density lipoprotein cholesterol levels in the high BSF group at the 28-day mark, were potentially attributable to the unique fatty acid composition of BSF meal. Moreover, this study potentiates future exploration into the efficacy of complete animal protein substitution with BSF meals on piglet nutrition and physiology, particularly in fattening pigs. The practical implementation of BSF meals in animal feed production holds promise for enhancing the sustainability of the swine industry.

Purpose: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy., Methods: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery., Results: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis., Conclusion: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Some carriers of human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a phase 1-2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1 or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, CSF inflammatory markers and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the phase 1-2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1-2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and four (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (P = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effects on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

It is not enough to just create medical practice guidelines; they are also required to be implemented into practice. Therefore, we surveyed specialists to determine the extent of the dissemination of the "HAM Practice Guidelines 2019," to quantify gaps, identify challenges, and understand needs in daily practice. The survey also revealed that the 25% of the specialists were unaware of the tests required for confirming human T-cell leukemia virus type I (HTLV-1) infection. Additionally, they had insufficient knowledge of the HTLV-1 infection. About 90.7% of the specialists agreed with the policy of determining treatment intensity based on disease activity. However, the implementation rate of cerebrospinal fluid marker measurement, which is useful for this assessment, was as low as 27%. Hence, it is important to use the findings of this study to further promote awareness about this issue.

Aim: The outcomes of cytoreductive surgery (CRS) for synchronous and metachronous colorectal peritoneal dissemination were investigated using the Japanese P classification and peritoneal cancer index (PCI)., Methods: CRS was performed in 111 cases of synchronous peritoneal dissemination and 115 cases of metachronous peritoneal dissemination. The P classification and PCI were determined at the time of laparotomy., Results: In the synchronous dissemination group, the 5-year overall survival rates after CRS in P1/P2 and P3 cases were 51% and 13%, respectively. Even for P3, 51% of the patients achieved macroscopic cytoreductive complete resection (CC-0), with a 5-year survival rate of 40%. When P3 cases were classified into PCI 0-9, 10-19, 20-29, and 30-39, CC-0 was achieved in 93%, 70%, 6%, and 0% of the cases, respectively, and the 5-year survival rate of PCI 0-9 was 41%. In the metachronous dissemination group, the 5-year survival rates were 62% for PCI 0-9 and 22% for PCI 10-19; 5-year survival was not observed in patients with a PCI ≥ 20. CC-0 was significantly associated with the postoperative prognosis in both synchronous and metachronous peritoneal dissemination., Conclusion: In cases of synchronous dissemination, CRS must be performed for P1 and P2 cases or those with a PCI < 10, while detailed examination using PCI is required for P3 cases. In cases of metachronous dissemination, CRS should be considered when the PCI score is <20., Competing Interests: The authors declare no conflicts of interest for this article., (© 2023 The Authors. Annals of Gastroenterological Surgery published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Gastroenterological Surgery.)

Both pseudomyxoma peritonei and Morgagni hernias in adults are rare clinical conditions. A 70-year-old woman who was diagnosed with pseudomyxoma peritonei with Morgagni hernia underwent cytoreductive surgery and primary repair. Pseudomyxoma peritonei causes increased intra-abdominal pressure that may lead to acquired congenital diaphragmatic hernia when there is a local fragility in the diaphragmatic musculature. Parietal peritonectomy of the right diaphragmatic peritoneum can safely remove the hernia sac. The high rate of infections associated with cytoreductive surgery causes hesitation for concurrent mesh repair for Morgagni hernia. This is the first report of pseudomyxoma peritonei with Morgagni hernia. Cytoreductive surgery including parietal peritonectomy of the right diaphragmatic peritoneum plus primary repair of hernial defect was performed safely and successfully, which achieved positive short-term results for patients with pseudomyxoma peritonei-associated Morgagni hernia., Competing Interests: Conflict of interestAll authors have no conflict of interests to declare., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The mechanisms behind reported decreases in plasma insulin and glucagon during hemodialysis (HD) are not clear. Here, we investigated these mechanisms during HD treatment and the characteristics of insulin and glucagon removal when using two super high-flux membranes. In an experimental study, clearance, adsorption rates, and reduction rates of insulin and glucagon were investigated when using cellulose triacetate (CTA) and polysulfone (PS) membranes in a closed circuit using bovine blood. In a clinical study, 20 diabetes patients with end-stage kidney disease who were stable on HD were randomly selected for two HD sessions with two different membranes. At 1 h after the initiation of HD, insulin and glucagon clearance were measured, and the reduction rates were also investigated. In the experimental study, the PS membrane showed significantly higher clearance, adsorption rates, and reduction rates of insulin and glucagon compared with the CTA membrane. Although glucagon was detected in the ultrafiltration fluids in both membranes, insulin was absent in the PS membrane. In the clinical study, both membranes showed significant reductions in plasma insulin and glucagon at each time point. The PS membrane showed significantly higher insulin clearance and reduction rates compared with the CTA membrane. The two membranes showed no significant difference in glucagon clearance, but the glucagon reduction rate was significantly higher with the PS membrane. Our findings show that HD with the two super high-flux membranes used removes significant amounts of glucoregulatory peptide hormones from plasma in patients with diabetes and end-stage kidney disease, potentially affecting their glucose metabolism.

Background: A limited number of studies have evaluated the masticatory indices of individuals with obesity who only chew their food a few times and for shorter duration or who were provided with an instructional intervention. This study aimed to examine the effects of a 6-month instructional mastication intervention on the body composition and biochemical indices in female patients with obesity., Methods: Female patients with obesity were randomly classified into a conventional treatment group (CTG; 12 individuals), which only received normal nutritional and exercise guidance, and a mastication intervention group (MIG; 16 individuals), which received an additional mastication guidance. The MIG received guidance on foods requiring increased number of chews and chewing duration, eating techniques, and the proper method of cutting foods., Results: Changes in the masticatory, body composition, and biochemical indices were compared before and after the 6-month intervention. The values of body composition indices decreased significantly in both groups; however, the rate of change in body mass index significantly decreased in the MIG. In addition, the values of biochemical indices were significantly decreased in the MIG compared with that in the CTG, which is attributed to the addition of mastication instruction to female patients with obesity., Conclusion: Increasing the number of chews and duration of chewing times for carbohydrates, which are staple foods, possibly contributed to weight loss and improvement of glucose metabolism., Trial Registration: UMIN, UMIN000025875. Registered on 27 Jan 2017., (© 2023. The Author(s).)

Background: Human T-cell leukemia virus type 1 (HTLV-1) causes HTLV-1-associated myelopathy (HAM), adult T-cell leukemia/lymphoma (ATL), HTLV-1-associated uveitis, and pulmonary diseases. Although both HAM and ATL show proliferation of infected cells, their pathogeneses are quite different. In particular, the pathogenesis of HAM is characterized by hyperimmune responses to HTLV-1-infected cells. Recently, we demonstrated the overexpression of histone methyltransferase EZH2 in ATL cells and the cytotoxic effects of EZH2 inhibitors and EZH1/2 dual inhibitors on these cells. However, these phenomena have never been studied in HAM. Furthermore, what effect these agents have on the hyperimmune response seen in HAM is completely unknown., Methods: In this study, we investigated histone methyltransferase expression levels in infected cell populations (CD4 + and CD4 + CCR4 + cells) from patients with HAM using microarray and RT-qPCR analyses. Next, using an assay system that utilizes the spontaneous proliferation characteristic of peripheral blood mononuclear cells derived from patients with HAM (HAM-PBMCs), we investigated the effects of EZH2 selective inhibitors (GSK126 and tazemetostat) and EZH1/2 dual inhibitors (OR-S1 and valemetostat, also known as DS-3201), particularly on cell proliferation rate, cytokine production, and HTLV-1 proviral load. We also examined the effect of EZH1/2 inhibitors on the proliferation of HTLV-1-infected cell lines (HCT-4 and HCT-5) derived from patients with HAM., Results: We found elevated expression of EZH2 in CD4 + and CD4 + CCR4 + cells from patients with HAM. EZH2 selective inhibitors and EZH1/2 inhibitors significantly inhibited spontaneous proliferation of HAM-PBMC in a concentration-dependent manner. The effect was greater with EZH1/2 inhibitors. EZH1/2 inhibitors also reduced the frequencies of Ki67 + CD4 + T cells and Ki67 + CD8 + T cells. Furthermore, they reduced HTLV-1 proviral loads and increased IL-10 levels in culture supernatants but did not alter IFN-γ and TNF-α levels. These agents also caused a concentration-dependent inhibition of the proliferation of HTLV-1-infected cell lines derived from patients with HAM and increased annexin-V(+)7-aminoactinomycin D(-) early apoptotic cells., Conclusion: This study showed that EZH1/2 inhibitors suppress HTLV-1-infected cell proliferation through apoptosis and the hyperimmune response in HAM. This indicates that EZH1/2 inhibitors may be effective in treating HAM., Competing Interests: DH and KA are employees of Daiichi Sankyo Co., Ltd. YY, MY, and KU received research funding from Daiichi Sankyo Co., Ltd. Daiichi Sankyo Co., Ltd., holds substance patents on the EZH1/2 inhibitors. St. Marianna University and Daiichi Sankyo Co., Ltd., hold patents for the application of the EZH1/2 inhibitors to HAM patients. YY and KA are named as inventors. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koseki, Araya, Yamagishi, Yamauchi, Yagishita, Takao, Takahashi, Kunitomo, Honma, Araki, Uchimaru, Sato and Yamano.)

Purpose: Second-hand smoke has adverse effects on oral health. This cohort study used a multilevel approach to investigate the association of second-hand smoke exposure, as determined by salivary cotinine level, with dental caries in adolescents., Methods: Data from 75 adolescents aged 11 or 12 years and 2,061 teeth without dental caries were analyzed in this study. Annual dental examinations to assess dental caries were conducted between 2018 and 2021. Salivary cotinine and Dentocult SM-Strip level were measured at baseline. Information on the smoking habits of parents, snack frequency, regular dental visits, and use of fluoride toothpaste was collected at baseline from parent-reported questionnaires., Results: During the 3-year follow-up, dental caries was noted in 21 adolescents and 43 teeth. Participants exposed to parental smoking had higher salivary cotinine levels than those whose parents did not smoke. The multilevel Cox regression model showed that a high salivary cotinine level was associated with the incidence of dental caries, after adjusting for potential confounding factors (hazard ratio, 3.39; 95% confidence interval 1.08-10.69)., Conclusion: This study suggests that the risk of dental caries is higher for adolescents who have high salivary cotinine levels attributable to second-hand smoke exposure.

In 1998, the Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment referred to as comprehensive treatment(COMPT). COMPT involves the complete removal of macroscopic tumors(cytoreductive surgery: CRS) and eradication of micrometastasis(MM)with neoadjuvant chemotherapy(NAC)plus intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC). This article provides a rationale for curative COMPT. Additionally, based on our experience, the selection criteria for treatment will be clarified., Rationale: The residual cancer cell burden is lowest immediately following CRS, and intraoperative HIPEC plays a crucial role in the treatment of patients with peritoneal surface malignancy (PSM). COMPT will fail if the number of the MM remaining after CRS exceeds the limit of complete eradication by intraoperative HIPEC(threshold). However, if the residual number of MM is less than the threshold, patients will respond positively to treatment., Patients and Methods: To validate the direct effect of HIPEC, laparoscopic HIPEC(LHIPEC)was performed, and changes in the peritoneal cancer index(PCI)were then evaluated. Complete cytoreduction and HIPEC carried out based on the concept of COMPT was performed in 171 gastric cancer(GC)patients with PCI≤12, 183 colorectal cancer(CRC)with PCI≤21 and 460 pseudomyxoma peritonei(PMP)patients with PCI≤28. The postoperative survivals rates were then analyzed., Results: After 1 cycle of LHIPEC, PCIs in GC and PMP were significantly reduced by 1.85 and 2.7 1 month after LHIPEC. However, PCI of CRC increased. Positive cytology at LHIPEC became negative in 57.6%, 42.9% and 60.9% of patients with GC, CRC and PMP, respectively. Median survival time(MST)for GC and CRC was 21.2 and 71.5 months, respectively MST of PMP was not reached. MST of PMP was not reached. Ten-year survival rates were 12.6%, 21.7% and 81.6%, respectively. Grade 5 complications for each disease were 0.8%, 1.0% and 1.1%, respectively., Conclusions: Complete cytoreductive surgery combined with intraoperative HIPEC may improve the long-term survival of patients with PSM who have PCIs less than the threshold levels, by keeping the mortality rates after CRS plus intraoperative HIPEC within acceptable levels.

Background and Purpose: In-stent restenosis (ISR) caused by in-stent intimal hyperplasia (ISH) may develop after carotid artery stenting (CAS), and often necessitates re-stenting. We investigated whether new ultrasound technique is useful for detecting carotid artery plaques prone to ISR., Purpose: Superb micro-vascular imaging (SMI) is a new color Doppler imaging technique for assessing low velocity blood flow such as neovascularization in carotid artery plaques. In this study, we attempted to identify associations between findings from carotid ultrasonography with SMI performed prior to CAS and in-stent restenosis after 6 months of CAS., Methods: This study investigated 19 patients (18 men; mean age, 72.4 years). Preoperative plaque evaluation was performed by magnetic resonance imaging, ultrasonography, and carotid angiography. Follow up angiography was performed in all patients at 6 months after CAS. ISR was defined as ISH resulting in >50% stenosis based on European Carotid Surgery Trialists criteria. We investigated whether SMI was useful as a predictor of ISR by chi-square test., Results: Preoperative mean stenosis rate according to North American Symptomatic Carotid Endarterectomy Trial methods in 19 patients was 61.3%. Neovascularization was observed on SMI in 10 patients (52.6%). Carotid angiography at 6 months after CAS revealed ISR in 4 patients, all of whom had shown neovascularization on SMI. A significant association was seen between findings of neovascularization on SMI and development of ISR (p = 0.033). In predicting ISR, neovascularization findings on SMI offered 100.0% sensitivity and 60.0% specificity., Conclusions: Preprocedural plaque characterization by carotid ultrasound with SMI appears useful for predicting ISR at 6 months after CAS., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

While people with obesity have been found to chew fewer times and for shorter durations, few studies have quantitatively evaluated mastication among this group. This study examined the relationship between the mastication characteristics of people with obesity and the factors correlated with obesity. To this end, 46 people with obesity and 41 healthy participants placed an earphone-style light sensor in the aperture of their outer ear. We also examined the partial correlation between this, their body composition, and various biochemical markers by gender. A two-way analysis of variance (ANOVA) regarding the masticatory index, gender, and the presence/absence of obesity for all three food items revealed the main effects in the gender difference and the presence/absence of obesity. Additionally, the number of times the salad was chewed showed an interaction between the gender and the presence/absence of obesity. In the BMI-corrected partial correlation analysis of the chewing index and the glucose/lipid metabolism index, the chewing time and the number of chews of all the food items negatively correlated with hemoglobin A1c(HbA1c), fasting plasma glucose (FPG), immunoreactive insulin (IRI), and homeostasis model assessment of insulin resistance (HOMA-R) in the female obese group. These findings might be used in weight-loss interventions for men with obesity and treatments that target the metabolic function among women with obesity.

Background: Despite advances in surgical techniques, long-term survival after esophagectomy for esophageal cancer remains unacceptably low, and more effective perioperative chemotherapy is expected. However, an important concern regarding the application of postoperative adjuvant chemotherapy is treatment toxicity. We aimed to evaluate the feasibility of adjuvant chemotherapy with S-1 in patients after esophagectomy., Methods: We investigated the tolerability of a 2-week administration followed by 1-week rest regimen of S1 as postoperative adjuvant therapy in 20 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy (NAC) and 22 patients who did not receive NAC during 2011-2020., Results: In the non-NAC group, the mean and median relative dose intensity (RDI) were 78.7% and 99.4%, respectively, and 11 patients (50%) had altered treatment schedules. The corresponding rates in the NAC group were 77.9% and 100%, respectively, and nine patients (45%) had altered treatment schedules, with no significant difference among the groups. Moreover, 17 patients (77.2%) in the non-NAC group and 16 patients (80.0%) in the NAC group continued S-1 treatment as planned for one year postoperatively, with no significant difference in the S-1 continuation rate (p = 0.500). Seventeen of 22 patients (77.3%) and 15 of 20 patients (75.0%) experienced several adverse events in the non-NAC and NAC groups, respectively. The frequency, severity, and type of adverse events were consistent among patients with and without NAC., Conclusions: S-1 could be safely and continuously administered as adjuvant chemotherapy for patients with esophageal cancer regardless of NAC. Long-term prognosis should be evaluated for S-1 to become the standard treatment after esophagectomy., (© 2022. The Author(s).)

We report the visible-light-induced in situ preparation of COCl 2 through the oxygenation of chloroform in the presence of chlorine dioxide, which leads to the safe constructions of carbamoyl chlorides with good-to-high yields and wide substrate scopes. In addition, this method can also be applied to the synthesis of various carbonates.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5'-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

This study investigated the effects of bamboo powder as an alternative feed for rabbits. The normal hay diet of rabbits was replaced with bamboo culm powder (10% and 20%) and fed to the rabbits until they were 90 days old. The blood samples were collected when the rabbits were 46, 66, and 90 days old to assess the effects of bamboo powder on blood parameters. The organs and intestinal contents were harvested at the age of 90 days, and the functions and morphologies of different organs were evaluated. The concentration of short-chain fatty acids (SCFAs) and the composition of microbiota in the cecum were measured. Substituting bamboo powder did not affect the growth, hematology profile, intestinal morphologies, and cecum SCFA concentration in rabbits. In contrast, it significantly altered the cecum microbiota composition, particularly the abundance of Ruminococcus and Bacteroides related to fiber degradation and Tyzzerella spp., associated with large intestine inflammation. These findings suggest that the substitution of hay with bamboo powder in rabbit diets does not negatively affect the overall health of rabbits and could be considered an alternative feed for rabbits; nevertheless, the protein and lipid deficiency in the bamboo powder should be taken into account., (© 2022 Japanese Society of Animal Science.)

Angiopoietin-like protein 2 (ANGPTL2) promotes chronic inflammation and plays a key role in the pathogenesis of heart failure. Cardiac rehabilitation (CR) is an integral component of heart failure management and has been shown to have anti-inflammatory effects. However, ANGPTL2 concentration in chronic heart failure patients undergoing CR has not been evaluated. This study aimed to investigate serum ANGPTL2 levels and their associated factors and compare the results with those of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with chronic heart failure undergoing phase III CR.A total of 56 patients were enrolled. Clinical characteristics including body composition, grip strength, exercise tolerance, duration of CR, blood counts and biochemistry, and echocardiographic parameters were evaluated for their association with serum ANGPTL2 and NT-proBNP levels.The median (first and third quartiles) value of ANGPTL2 was 4.05 (2.70-5.57) ng/mL. Clinical parameters that correlated with serum ANGPTL2 levels were body weight, body mass index, body fat mass, body fat percentage, anaerobic threshold (AT), C-reactive protein, and total protein (TP), which were mostly distinct from those that correlated with serum NT-proBNP levels. A multivariate analysis revealed that AT and TP were independent factors related to ANGPTL2 levels, whereas age, left ventricular ejection fraction, and left atrial dimension were independently related to NT-proBNP levels.These observations suggest that CR increases the exercise tolerance and exhibits anti-inflammatory effects simultaneously, and this situation is reflected by decreased serum ANGPLT2 and TP levels. ANGPTL2 may be a useful marker of inflammation and impaired exercise tolerance in patients with chronic heart failure.

Background: An effective strategy for weight loss in patients who are overweight or obese is to reduce body fat mass while maintaining skeletal muscle mass. Adiponectin and myostatin are affected through changes in body composition due to weight loss, and examining their dynamics may contribute to strategies for maintaining skeletal muscle mass through weight loss. We aimed to examine the relationships among myostatin, adiponectin, and body composition, depending on the extent of weight loss, in patients with obesity undergoing a weight loss program., Methods: We examined 66 patients with obesity (age: 46.8 ± 14.0 years, body mass index: 34.3 [31.0-38.4] kg/m 2 ) attending a hospital weight loss program. We categorized the patients into two groups, namely an L group (those with a weight reduction of < 5% from baseline) and an M group (those with a weight reduction of > 5% from baseline). All patients underwent blood tests and were assessed for body composition, insulin resistance, adipocytokine and myokine levels, exercise tolerance, and muscle strength at baseline and post-intervention., Results: Serum myostatin and adiponectin levels increased post-intervention in both groups. Body weight and %fat decreased, and the rate of lean body mass (%LBM) increased in both groups. Exercise capacity and muscle strength improved in the M group only. Change in (⊿) myostatin correlated with ⊿%fat, ⊿%LBM, and ⊿adiponectin. ⊿adiponectin (β = - 0.262, p = 0.035) was an independent predictor of ⊿myostatin., Conclusions: Myostatin and adiponectin might cross-talk and regulate changes in skeletal muscle and fat mass with or without successful weight loss. These findings indicate that evaluating serum myostatin and adiponectin levels in clinical practice could be used to predict the effects of weight loss and help prevent skeletal muscle mass loss.

We herein report a case of penile pyoderma gangrenosum that was successfully treated with prednisolone and by urethrocutaneostomy without penectomy. A man in his 50s visite dour department because of painful urination. Pyuria and redness of the external urethral meatus were present. Treatment for urethritis with antibiotics did not improve his symptoms, and a painful ulcer and fistula formation between the glans and urethra subsequently developed. Microbiological cultures revealed no growth, and punch biopsy showed only nonspecific inflammation, leading to a diagnosis of penile pyoderma gangrenosum. We initiated prednisolone (PSL) at 40 mg once daily following placement of an indwelling suprapubic cystostomy tube for dysuria. However, the treatment was ineffective. Therefore, the dosage of PSL was increased to 65 mg once daily. The ulcer disappeared， but urethral stricture remained. Six hundred days after PSL treatment, we performed urethrocutaneostomy. The patient became free of the cystostomy and was able to urinate spontaneously. In recent years, there has been an increasing number of reports of penile preservation in the treatment of penile pyoderma gangrenosum, but knowledge regarding which patients require urethral surgery is lacking. Urologists should keep in mind increased susceptibility to infection, pathergy and possible recurrence, when considering urethral surgery for penile pyoderma gangrenosum.

Dopamine supersensitivity psychosis (DSP) frequently arises with long-term antipsychotic treatment and accounts for a significant proportion of treatment-resistant schizophrenia. The mechanism underlying DSP is thought to be a compensatory increase in dopamine receptor density in the striatum caused by long-term antipsychotic treatment. Previous animal studies have reported that antipsychotics increase serotonin 5-HT2A receptor density in the striatum and that 5-HT2A receptor blockers suppress dopamine-sensitive psychomotor activity, which may be linked to the pathophysiology of DSP. In this paper, we describe a patient who was hospitalised with treatment-resistant schizophrenia. Following treatment with high-dose antipsychotic polypharmacy for 10 weeks, the patient experienced worsening of psychotic and extrapyramidal symptoms. The patient was then started on second-generation antipsychotic asenapine while other antipsychotics were tapered off, resulting in improvement of these symptoms. Retrospectively, we presumed that the high-dose antipsychotic polypharmacy caused DSP, which was effectively treated by the potent 5-HT2A receptor antagonism of asenapine., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 47-year-old man who was previously hospitalized three times due to bacterial meningitis experienced a headache and posterior neck pain in May. He was admitted to our hospital because of a fever 3 h later. He was fully conscious and febrile, with a headache and signs of meningeal irritation. A cerebrospinal fluid examination showed an increased number of cells with polynuclear cell predominance and decreased glucose levels, leading to the diagnosis of bacterial meningitis. Steroid and antibiotic treatment was initiated, at which time, large amounts of nasal discharge were observed. Cisternal scintigraphy was performed, and cerebrospinal fluid was detected in the nasal discharge. The cause was idiopathic, and endoscopic repair was performed. The nasal fluid leakage was suggested to be the cause of the recurrent bacterial meningitis in this case.

Background: Chemosensitivity testing, including collagen gel droplet-embedded culture drug sensitivity test, has proven to be a useful tool in therapeutic decision-making. This retrospective analysis investigated chemosensitivity testing of peritoneal metastases collected during cytoreductive surgery (CRS), and its impact on survival in patients with colorectal cancer., Methods: All patients with peritoneal metastasis from colorectal cancer who underwent CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) between November 2008 and October 2014 were included. The growth inhibition rate was expressed as the ratio between the image density after treatment (T) and that before treatment (control, C). Tumours with a reduction in T/C ratio of less than 20 per cent were defined as resistant and those with a reduction of 20 per cent or more as sensitive. Groups were compared for overall (OS) and disease-free (DFS) survival., Results: Of 84 eligible patients, 81 received neoadjuvant chemotherapy (NACT), including 56 patients with an oxaliplatin-based regimen. Mean(s.d.) follow-up was 23·4(22·9) months. The median overall survival of all patients was 19·0 (i.q.r. 5·7-36·1) months, with a progression-free survival time of 10·1 (4·5-17·0) months. Patients who received oxaliplatin-based NACT had significantly altered chemosensitivity to oxaliplatin; only 20 of 51 such patients showed chemosensitivity to oxaliplatin compared with 16 of 24 who did not undergo oxaliplatin-based NACT (P = 0·046). However, patients who showed chemoresistance to oxaliplatin had similar OS to those with chemosensitivity (18·8 versus 18·1 months; P = 0·835). The choice of HIPEC agents in patients who received oxaliplatin-based NACT did not significantly influence survival (oxaliplatin versus mitomycin C: median OS 20·6 (10·9-24·8) versus 19·0 (10·5-34·6) months, P = 0·811; DFS 6·6 (2·8-25·7) versus 9·3 (4·1-13·9) months, P = 0·191)., Conclusion: Patients who had oxaliplatin-based NACT showed a higher rate of chemoresistance to oxaliplatin at the time of CRS and HIPEC. The impact of chemosensitivity testing on OS remains unclear and needs further investigation., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

[Purpose] We aimed to evaluate oxygen uptake adjusted by total skeletal muscle mass in patients with cardiovascular disease with or without type 2 diabetes mellitus. [Participants and Methods] The participants included 54 males ≥50 years of age without heart failure who underwent cardiopulmonary exercise testing during cardiac rehabilitation. We divided the participants into two groups: patients with type 2 diabetes mellitus (DM group) and patients without type 2 diabetes mellitus (NDM group). [Results] We found no significant differences in age, weight, fat mass, or skeletal muscle mass between the groups. There were also no differences in cardiac function, body composition, and heart rate response. The DM group showed significantly lower peak oxygen uptake values adjusted by skeletal muscle mass, despite the absence of significant differences in skeletal muscle mass. A significant positive correlation was found between peak oxygen uptake and age, weight, and skeletal muscle mass. Stepwise regression analysis revealed that age, skeletal muscle mass, and medical history of diabetes were independent predictors of absolute peak oxygen uptake. [Conclusion] Peak oxygen uptake adjusted by skeletal muscle mass in patients with cardiovascular disease and type 2 diabetes mellitus is lower than that in those without type 2 diabetes mellitus., (2021©by the Society of Physical Therapy Science. Published by IPEC Inc.)

Background: Adiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity., Methods: Overall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples., Results: The serum adiponectin level was 2.9 μg/mL (1.7-4.1 μg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1-2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001)., Conclusion: The serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass., Competing Interests: The authors have declared that no competing interests exist.

Objectives: In-stent intimal restenosis (ISR) caused by neointimal hyperplasia can develop <24 months after carotid artery stenting (CAS). The utility of plaque imaging by carotid ultrasonography (US) or magnetic resonance imaging (MRI) has been investigated for the prediction of ipsilateral stroke. We aimed to investigate whether these imaging techniques are useful for detecting carotid plaques prone to ISR., Materials and Methods: We examined 133 patients (mean age of 72.1 ± 8.4 years old) that received CAS at a single hospital from 2014 to 2018. A pre-CAS carotid plaque evaluation was performed by carotid angiography, duplex carotid US, and black-blood carotid artery MRI (BB-MRI). The mean stenosis rate was 71.0 ± 12.3% by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) methods. Follow-up carotid angiography was performed 6 months after CAS in all patients according to a predefined protocol. ISR was defined as in-stent intimal hyperplasia more than 50% stenosed based on the NASCET criteria. The selection of the stent type was at the discretion of the treating physician. Predictors of ISR were determined by multivariate logistic regression analysis., Results: Follow-up angiography demonstrated ISR in 33 patients (24.8%). In 44 patients, more than two stents were deployed. Univariate logistic regression analyses demonstrated echolucent lesion, floating plaque, complete occlusive or pseudo-occlusive lesion, and closed-cell stent use as significantly associated with ISR (>50%). Multivariate logistic regression analysis demonstrated that echolucent lesion (OR 4.667, 95% CI 1.849-11.779) and closed-cell stent use (OR .378, 95% CI .148-.968) were significantly associated with ISR., Conclusions: Preprocedural plaque characterization by carotid US appeared to be useful to predict ISR 6 months after CAS., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: While the intravenous recombinant tissue plasminogen activator (rt-PA) therapy for acute ischemic stroke patients with cancer is recommended when survival of ≥ 6 months is expected, the risk factors for death and stroke recurrence within 6 months after stroke are not well known. Thus, we aimed to identify markers for death and recurrence risks within six months from stroke onset in patients with cancer., Materials and Methods: In a retrospective cohort study, the subjects comprised acute ischemic stroke patients with cancer hospitalized at St. Marianna University hospital from 2008 through 2019. To evaluate the associations between the clinical factors within 24 h of the initial stroke and death or stroke recurrence events within 6 months from stroke onset, Logistic analysis and Cox proportional hazards regression analysis was used respectively. Next, the optimal cutoff point of markers for different mortality groups was determined using the receiver operating characteristic curve analysis and cumulative outcome rate of each group was compared using the Kaplan-Meier method., Results: Among 194 patients with cancer who developed acute stroke, 167 were ultimately selected for analysis. 47 subjects (28.14%) passed away within 6 months following stroke onset, and 20 subjects (11.98%) had stroke recurrence. High D-dimer levels, low fibrinogen levels, high Glasgow prognostic scores (GPS), and multiple vascular territory infarctions was independently associated with death, where higher death rate was significantly confirmed in the group with D-dimer levels of ≥3.95 mg/dl, fibrinogen levels <277.5 mg/dl and GPS scores of 2. Low fibrinogen level, lack of antithrombotic therapy, and the presence of metastasis were associated with stroke recurrence., Conclusions: When patients with cancer suffer stroke, D-dimer levels, fibrinogen levels, GPS, and multiple vascular territory infarctions would be associated with the risk of death within 6 months. Low fibrinogen levels, lack of antithrombotic therapy, and the presence of metastasis correlated with high risk of stroke recurrence., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: A new treatment strategy involving cytoreductive surgery (CRS) combined with perioperative intraperitoneal (IP) chemotherapy was proposed in 1999 by the Peritoneal Surface Oncology Group International, and the strategy is now justified as a state-of-the-art treatment to improve the long-term survival of patients with peritoneal metastasis (PM). To achieve cure in the patients with PM, complete removal of macroscopic tumors and eradication of micrometastasis on the peritoneum, left after CRS are essential. Systemic chemotherapy is not indicated for the treatment of PM. In contrast, intraperitoneal (IP) chemotherapy brings about significantly higher locoregional dose intensity in the peritoneal cavity and subperitoneal tissues. In combination with anticancer drugs, hyperthermia enhances cytotoxicity against cancer cells., Area Covered: This article provides a systematic overview of PM from various cancers including gastric, colorectal, small bowel, appendiceal cancer, and mesothelioma. It also includes all the essential aspects of therapy., Expert Opinion: CRS plus perioperative intraperitoneal chemotherapy is safe with acceptable morbidity and mortality. It is justified as a standard treatment to improve the long-term survival of patients with PM and is now performed with curative intent for PM from various malignancies.

Signet ring cell subtype (SRC) of colorectal cancer (CRC) is a rare subtype and occurs in approximately 1% of all patients with CRC. Patients with peritoneal metastasis (PM) of SRC have a poor prognosis, and this subtype is frequently considered as a contra-indication for extensive surgical treatment. This retrospective study from two dedicated peritoneal surface malignancy centers in Japan included all patients treated with CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between July 1994 and December 2017 from a prospectively maintained database. Preoperative, operative, and postoperative parameters were recorded, including complication rates and follow-up. Sixty of the 320 patients treated with CRS due to CRC were diagnosed with SRC subtype. The mean age of the patients was 51.4 years, and the mean peritoneal carcinomatosis index (PCI) was 13.1. Complete cytoreduction was achieved in 61.7% of cases. The postoperative morbidity rate was 25% and the mortality rate was 1.7%. The median overall survival (OS) was 14.4 months. Cox regression analysis revealed small bowel PCI > 2 (hazard ratio (HR) 6.5; p = 0.008) as the most important factor for OS. With accurate patient selection (e.g., PCI ≤ 12 or small bowel PCI ≤ 2), even patients with PM of CRC with SRC subtype may benefit from CRS and HIPEC, with median OS from 17.8 to 20.8 months and 5-year OS of 11.6%.

Neoadjuvant intravenous chemotherapy in patients with pseudomyxoma peritonei (PMP) has not shown convincing results. The effectiveness of neoadjuvant intraperitoneal (IP) chemotherapy has never been reported. This prospective, non-randomized phase II study included patients with PMP treated between May 2017 and December 2018, who were not considered suitable for primary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The majority of patients were treated with laparoscopic HIPEC (oxaliplatin 200 mg/m 2 , 60 min, 43 °C). IP chemotherapy was started 2 weeks after docetaxel 40 mg/m 2 + cisplatin 40 mg/m 2 , accompanied by oral S1 (tegafur, gimeracil, and oteracil) (50 mg/m 2 ) for 14 days, followed by one week rest. Clinical parameters and complications were recorded. In total, 22/27 patients qualified for CRS and HIPEC after neoadjuvant treatment. A complete cytoreduction (Completeness of cytoreduction Score 0/1) could be achieved in 54.5%. The postoperative morbidity rate was 13.6% and mortality was rate 4.5%. In total, 20/22 patients had major pathological tumor responses. The mean drop in CEA was 28.2% and in the peritoneal carcinomatosis index (PCI) was 2.6. Positive or suspicious cytology turned negative in 69.2% of patients. Thus, for PMP patients who were not amenable for primary surgery, the majority received complete cytoreduction after treatment with neoadjuvant IP chemotherapy, with satisfying tumor regression and with low complication rates. The oncological benefit in terms of survival with this new treatment regimen needs to be proven.

Objective: DNA methylation is an epigenetic mechanism that regulates gene expression. The obesity-related ( FTO ) gene is the first gene found to be associated with fat mass and obesity. However, no studies have examined the relationship between weight-loss intervention effect and FTO methylation in obese individuals with whole blood DNA. The purpose of this study was to quantify FTO whole blood DNA methylation and investigate the relationship between body composition, exercise capacity, and blood parameters with a 6-month weight-loss program intervention., Participants and Methods: Eighteen female participants (mean age, 50.6 ±12.1 years, body mass index (BMI), 33.5 ± 6.2 kg/m 2 ) who completed a 6-month weight-loss program at the obesity outpatient department at the Health Science Center of Kansai Medical University Hospital from March 2017 to October 2018 were included in the analysis. Participants were randomized into a normal treatment group (NTG) and a group with additional resistance training (RTG). Body composition, exercise tolerance and metabolic index were measured in each participant. DNA methylation status in whole blood samples was determined using pyrosequencing. All measurements were taken during the first visit and at the 6-month post-intervention visit., Results: The methylation rate was significantly decreased in the NTG in CpG1 (p=0.011) and total value of CpG (p=0.011), whereas in the treatment group containing resistance training (RTG), CpG3 (p=0.038) was increased significantly. Furthermore, the independent factors that determine %CpG3 of RTG were visceral fat area change rate (%VFA) (β = -0.568, P = 0.007, R2 = 0.527) and resistance training (β = 0.517, P = 0.012, R2 = 0.527), which have been extracted., Conclusion: A 6-month weight-loss program, including resistance training, may be associated with decreased visceral fat area changes and increased RTG CpG3 methylation changes. However, further replication studies with larger sample sizes are warranted to verify the findings of this study., Competing Interests: The authors report no conflicts of interest related to this work., (© 2020 Nishida et al.)

The morphological changes of Nafion thin films with thicknesses from 10 to 200 nm on Pt substrate with various annealing histories (unannealed to 240 °C) were systematically investigated using grazing incidence small-angle X-ray scattering (GISAXS) and grazing incidence wide-angle X-ray scattering (GIWAXS). The results revealed that the hydrophilic ionic domain and hydrophobic backbone in Nafion thin films changed significantly when the annealing treatment exceeded the cluster transition temperature, which decreased proton conductivity, due to the constrained hydrophilic/hydrophobic phase separation, and increased the crystalline-rich domain. This research contributed to the understanding of ionomer thermal stability in the catalyst layer, which is subjected to thermal annealing during the hot-pressing process.

Background: It is known that patients on hemodialysis (HD) are prone to developing zinc deficiency due to removal of zinc by HD, inadequate dietary intake, and reduced gastrointestinal zinc absorption. However, the prevalence of zinc deficiency in patients on peritoneal dialysis (PD) has not been well established., Methods: Serum zinc levels were compared between 47 patients on PD and 47 patients on HD matched for age, sex, and duration of dialysis. A serum zinc level < 60 μg/dL was defined as clinical zinc deficiency and a level of 60-80 μg/dL as subclinical zinc deficiency. The prevalence of zinc deficiency and associated clinical factors were determined in both groups., Results: Clinical zinc deficiency was found in 59.6% of the PD group and 70.2% of the HD group ( p = 0.391). Subclinical zinc deficiency was found in 40.4% of the PD group and 29.8% of the HD group. Age, body mass index, and serum albumin level were identified as independent predictors of zinc deficiency in the PD group by multivariate analysis., Conclusions: A higher prevalence of clinical and subclinical zinc deficiency was found in patients on PD. The rates were comparable between patients on PD and those on HD after adjustment for confounding factors.

The present study demonstrated prognostic factors for long-term survival in patients after a comprehensive treatment (CHT) for peritoneal metastasis (PM) from gastric cancer (GC)., Materials and Methods: Among 419 patients treated with neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), 266 (63.5%) patients received complete resection (CC-0) of the macroscopic tumors. In total, 184 (43.9%) patients were treated with postoperative systemic chemotherapy., Results: All patients treated who received incomplete cytoreduction (CC-1) died of GC within 6 years. In contrast, 10- year survival rates (-YSR) of CC-0 resection were 8.3% with median survival time (MST) of 20.5 months. Post-NIPS peritoneal cancer index (PCI) ≤11, and pre-NIPS PCI ≤13 were the significant favorable prognostic factors. Patients with numbers of involved peritoneal sectors ≤5 survived significant longer than those with ≥6. Both negative pre- and post-NIPS cytology was associated with significant favorable prognosis. Multivariate analyses identified pre-PCI (≤13 vs. ≥14), and cytology after NIPS (negative cytology vs. positive cytology) as independent prognostic factors. Ten year-survivors were found in patients with involvement of the greater omentum (9%), pelvic peritoneum (3%), para-colic gutter (13.9%), upper jejunum (5.6%), lower jejunum (5.5%), spermatic cord (21.9%), rectum (9.5%), ureter (6.3%), ovary (6.7%), and diaphragm (7.0%) at the time of cytoreduction. Twenty-one patients survived longer than 5 years, and 17 patients are still alive without recurrence., Conclusions: GC-PM should be removed aggressively, in patients with PCI after NIPS ≤11, PCI before NIPS ≤13, mall bowel PCI ≤2, and complete cytoreduction should be performed for metastasis in ≤5 peritoneal sectors.

Background: In patients with acute ischemic stroke, current guidelines recommend maintaining blood glucose levels in a range of 140-180 mg/dL and closely monitoring to prevent hypoglycemia (<60 mg/dL). We aimed to assess glucose variability by continuous glucose monitoring (CGM) and to demonstrate the risk of acute ischemic stroke patients with glucose levels outside of the glucose management recommendations., Methods: Patients with ischemic stroke admitted within 7 days after onset were prospectively enrolled, and their blood glucose levels were monitored every 15 minutes for 72-hour period using the FreeStyle Libre Pro. Multivariate logistic regression analyses were used to analyze potential predictors for hyperglycemic (>180 mg/dL) and hypoglycemic (<60 mg/dL) events., Results: A total of 39 acute ischemic stroke patients (mean age 75.9 ± 11.5 years) were enrolled, and CGM was started from 58.6 ± 41.9 hours after stroke onset. CGM showed hypoglycemic events in 19 patients and hyperglycemic events in 21 patients, and the frequencies of hypo- and hyperglycemic events during CGM were 10.1 ± 15.7% and 11.9 ± 22.5%, respectively. Hypoglycemic events were mainly observed in the night-time in patients with normoglycemia at admission. Logistic regression analyses demonstrated significant associations between the blood glucose level at admission and hypo- and hyperglycemic events on CGM., Conclusions: This study of CGM found that many stroke patients have blood glucose levels outside the recommended guideline range in the acute phase. Blood glucose level on admission may be used as a predictor for hypo- and hyperglycemic events after admission., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment, named comprehensive treatment for peritoneal metastasis(PM)from colorectal cancer(CRC). The present study demonstrated the efficacies of the treatment regarding the peritoneal sectors and organs involved with PM from CRC., Materials and Methods: Among 365 patients received laparotomy, 278 CRC patients with PM underwent complete cytoreductive surgery(CC-0)., Results: After CC-0 resection Grade 3, Grade 4, and Grade 5 postoperative complication were found in 20(7.2%), 26(9.3%), and 6(2.2%). Five- and 10-year survival rate(YSR)of CC-0 resection were 24.5%, and 11.6% with median survival time(MST)of 42.0 months. Regarding the peritoneal cancer index(PCI)of small bowel(SB-PCI), all patients of PCI B3 died of the disease. In contrast, 10-YSR of patients with SB-PCI of 0, 1, and 2 were 26.1%, 19.5%, and 6.2%, respectively. Ten-YSR of patients with the number of involved peritoneal sectors C9 ranged from 6.9% to 29.8%. MST of patients with PM in each peritoneal sector(sector 0 to sector 8)ranged from 26.4 months to 49.2 months, and 10-YSR ranged from 4.2%to 17.2%. Ten-YSR of patients with involvement of rectum, stomach, liver capsule, seminal vesicle, ureter, uterus, or ovary ranged from 0% to 16.9%., Conclusions: From the present data, PM should be removed aggressively to achieve complete cytoreduction, when the patients with PCIC26, involved peritoneal sectorsC9 and SB-PCIC2 are supposed to receive complete cytoreduction of PM.

Background: Toe grip-related training requires individuals to actively exercise muscles that are not frequently used; therefore, it may improve not only toe grip strength but also cognitive function. The purpose of this study was to examine the effects of toe grip-related training on predictors of physical performance and cognitive function in nursing home residents., Methods: A total of 35 nursing home residents (35 left and 35 right feet; mean age, 82.1 ± 7.9 years) were included in this study. The participants were divided into two groups: a training group and a control group. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function of the participants, and the Fall Risk Index (FRI) was used to evaluate the risk of falls. Toe grip-related physical function was also assessed. Baseline endpoints were evaluated and the effects of toe grip-related training were examined following a 12-week training intervention., Results: The training group showed significant improvements in MMSE score, FRI score, toe grip strength, and the toe skill (TS) test; however, the control group did not show these changes. The training group showed significant increases in Δ MMSE, Δ toe grip strength, and Δ TS (right foot) than the control group. Stepwise regression analysis revealed that Δ toe grip strength is an independent factor of Δ MMSE., Conclusions: Toe grip training improves not only toe grip strength itself, but also cognitive function. Furthermore, change in toe grip strength was an independent factor of change in MMSE in those populations., Trial Registration: UMIN, UMIN000027437 . Registered on 26 May 2017.

Aim: In-stent intimal hyperplasia (ISH) observed after carotid artery stenting (CAS) may lead to in-stent restenosis. We aimed to investigate whether contrast-enhanced carotid ultrasonography (CEUS) and magnetic resonance imaging (MRI) plaque imaging prior to CAS are predictive for ISH at 6 months after CAS., Material and Method: A total of 14 patients (13 men, 1 woman; mean age, 74.2 years) were prospectively enrolled. CEUS and MRI plaque imaging were performed before CAS. ISH was diagnosed by carotid angiography at 6 months after CAS. Patients were divided into two groups based on the thicknessof ISH and age, risk factors, enhancement in CEUS, MRI plaque imaging and number of replaced stents were compared between groups., Results: Carotid angiography at 6 months after CAS revealed ISH in 10 patients. Plaque enhancement on CEUS was observed in 6 patients, all of whom showed ISH. A significant association was seen between plaque enhancement on CEUS and development of ISH (χ2 test, CEUS enhancement (+) 100% vs. CEUS enhancement (-) 50% p=0.040). Carotid plaques in 12 patients were diagnosed as unstable by MRI plaque imaging. Presence of ISH was significantly associated with unstable plaque diagnosed by MRI plaque imaging (χ2 test, unstable 83% vs. stable 0%; p=0.016)., Conclusion: Carotid plaque MRI and CEUS may be useful to predict ISH after CAS.

Background and Objectives: The current standard of treatment for malignant peritoneal mesothelioma(MPM)is cytoreductive surgery(CRS)plus perioperative intraperitoneal or systemic chemotherapy(comprehensive treatment), The present study was performed to clarify the prognostic factors of PMP after comprehensive treatment., Methods: Among 63 patients with MPM, male and female patients were 34 and 29. CRSwas performed in 47 patients and complete cytoreduction(CC-0) was performed in 14(22%)patients. Mean numbers of resected peritoneal sectors and organs were 5.2(1-13), and 2.9(0- 9), respectively. Hyperthermic intraperitoneal chemoperfusion(HIPEC)was performed in 27 patients. Grade 1/2, Grade 3, and Grade 4 complications were experienced in 5, 6, and 3 patients, respectively. One patient died of sepsis, and the mortality rate was 2.3%. Independent prognostic factors for favorable prognosis were performance of HIPEC, peritoneal cancer index (PCI)score C12, no distant metastasis and histologic epithelial type. Relative risk of no HIPEC, PCI score B13, presence of distant metastasis and non epithelial type were 7.69, 22.1, 3.6 and 3.9, respectively., Conclusions: Risk factors for death after comprehensive treatment were no HIPEC, PCI score B13, and non epithelial type. However, only 11(17%)patients showed PCI score C12. Accordingly, PCI score should be reducedC12 before CRSby neoadjuvant chemotherapy.

Phage therapy is getting considerable attention as a method for prophylaxis of food poisoning caused by Escherichia coli O157:H7, an important pathogen causing life-threatening bloody diarrhea. Despite previous studies have shown the feasibility of phage therapy to E. coli O157:H7, promising results have not been obtained in vivo yet. A major drawback of phage therapy is that bacteriophages have high specificity and cannot infect all the sub-strains of a particular pathogenic strain. To overcome this hurdle, we thought to establish a way to artificially expand the host-range of E. coli O157:H7-specific phages. To develop a proof-of-concept for this method, we focused on T2 phage, which cannot infect E. coli O157:H7 strains, and PP01 phage, which displays broad infectivity to them, and attempted to make T2 phage able to infect E. coli O157:H7 as efficiently as PP01. We report the trials of T2 genome editing using the CRISPR/Cas9 system and the modification of both long and short tail fibers of this phage based on comparison with PP01. The resultant recombinant showed the adsorption rate comparable to PP01. Thus, we provided the evidence that the short tail fiber of PP01 plays an important role in adsorption to E. coli O157:H7., (© FEMS 2019.)

Background and Objectives: Treatment failure after complete cytoreduction for appendiceal mucinous carcinoma peritonei (AMCP)has not been fully investigated. The present study was performed to clarify the risk factor for recurrence after complete cytoreduction for AMCP., Methods: A total of 400 patients with AMCP who underwent complete cytoreductive surgery combined with perioperative chemotherapy were investigated., Results: Documented recurrence was developed in 135 (33.8%)patients. The 5- and 10-year progression-free survival was 51% and 49%, respectively. By multivariate analysis, histological subtype of peritoneal disease(high-grade AMCP[AMCP-H]and AMCP-H with signet ring cells), serum CA19- 9 level, and PCIB20 were significantly associated with reduced progression-free survival. In contrast, histologic subtype of mucin without epithelial cells(MWEC)showed the lowest risk for recurrence. Eighty-six patients had localized intra-abdominal recurrence, and 42 patients had diffuse peritoneal recurrence. Recurrence was found in the various peritoneal sectors. Eighty-one patients underwent complete cytoreduction for the recurrence, and the overall survival 5-year survival rate after secondary cytoreduction was 49%., Conclusions: Risk factors for recurrence were histologic subtype, PCI cutoff level, and serum CA19-9 levels. Aggressive second attempt of cytoreduction in patients with localized recurrence improved the survival.

In this review, Japanese experience of cytoreductive surgery and perioperative chemotherapy is described. The new concept of peritoneal metastasis (PM) type, i.e., trans-mesothelial, trans-lymphatic, and superficial growing metastasis type was proposed in 2012. Surgeons should perform peritonectomy according to the type of PM. Since 1980, Japanese surgical oncologists have been spearheading the use of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for PM from gastric cancer. Two RCTs were conducted to verify the effect of HIPEC for the prophylaxis of peritoneal recurrence after curative resection of advanced gastric cancer. These two studies indicated that HIPEC is effective in preventing peritoneal recurrence of gastric cancer with serosal invasion. In 2002, intraperitoneal chemotherapy using taxans was developed for the treatment of PM from gastric cancer and led to the development of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), which was reported in 2006. In 2009, extensive intra-operative peritoneal lavage (EIPL) was developed, and contributed to the remarkable improvement in survival of patients with positive lavage cytology as demonstrated by prospective randomized clinical trials. In 2017, the Peritoneal Surface Oncology Group International proposed the value of complete cytoreduction and peritoneal cancer index cut-off as independent prognostic factors after CRS for gastric cancer with PM. Founded in 2016, the Japanese/Asian School of Peritoneal Surface Oncology (JASPSO) trains beginners to perform CRS and HIPEC safely. Sixteen students have already graduated from JASPSO and started to perform the treatment in their home countries.

Carotid artery atherosclerosis is one of the major risk factors for ischemic stroke. Intraplaque neovascularization (IPN) is one of the steps toward the development of vulnerable plaque. Superb microvascular imaging (SMI) is a new ultrasonographic technique for visualizing low-velocity and microvascular flow by clutter suppression to extract flow signals from large to small vessels and enables visualization of intraplaque microvascular flow (IMVF) without echo contrast media. We aimed to investigate the association between IMVF signal in SMI and MRI plaque imaging among patients with atherosclerotic carotid stenosis. We prospectively enrolled patients (>18 years old) with mild to severe carotid stenosis (more than 50% in cross-sectional area) diagnosed by carotid ultrasonography between August 2017 and April 2018, irrespective of sex and history of stroke. A total of 40 patients (31 men, 9 women; mean age, 75.1 ± 10.0 years) were enrolled. SMI revealed IPN findings in 21 patients. SMI clearly visualized the direction of pulsatile flow movement in microvessels and IPN was easily classified into the two types of Type V (n=2) and Type E (n=19). Multivariate logistic regression analysis presented that microvascular flow signal in carotid plaque on SMI was identified as a significant predictor of intraplaque hemorrhage as evaluated by MRI (OR, 8.46; 95%CI, 1.44-49.9; p=0.018). This study demonstrated a significant association between the presence of IMVF signal in SMI and intraplaque hemorrhage characterized by high-intensity lesions on MRI T1-FFE images., (Copyright © 2018. Published by Elsevier Inc.)

Background: Toe grip strength is the force of a toe on a surface. The objective of this study was to investigate the relationship between falls in middle-aged individuals and physical strength factors such as toe grip strength and knee extension strength., Methods: The subjects were 194 middle-aged individuals (388 feet) who were independent in daily life, received no nursing care, and participated in a health sports event organized by a sports club. We evaluated the body composition, blood pressure, vascular age, systemic response, bone density, knee extension strength, and toe grip strength, and examined their relationship using a self-administered questionnaire survey., Results: The fall, near-fall, and no fall groups included 7, 36, and 151 subjects, respectively; the high and low risk groups included 43 and 151 subjects, respectively. Logistic regression analysis was performed with risk of falls as the dependent variable, and factors that showed a significant difference in the comparison of the high and low risk groups as independent variables. In this analysis, toe grip strength and diastolic blood pressure were identified as independent risk factors for a fall., Conclusions: Toe grip strength is an independent risk factor for falls, and improvement of toe grip strength might prevent falls.

Background: Many studies have confirmed that the size and location of necrotic lesions are major factors that affect the prevalence of collapse and prognosis in patients with osteonecrosis of the femoral head (ONFH). Although several classification systems categorize and quantify ONFH, there is no agreement on which one is most useful for the purpose., Questions/purposes: We compared the Steinberg, modified Kerboul, and Japanese Investigation Committee (JIC) classifications of ONFH in terms of (1) the correlation among the three different classification systems. We further examined (2) the inter- and intraobserver reliability of the three classification systems and (3) the association of higher grades within each classification and the risk of subsequent collapse., Methods: Between January 2000 and December 2014, we treated 101 hips in 74 patients for precollapse ONFH, diagnosed either on plain radiographs or MRI. Of those, one patient (1%) died, six patients (8%) were lost to followup, and two patients (3%) underwent osteotomy before 2 years, leaving 86 hips in 65 patients (88%) for analysis here. Three-dimensional spoiled gradient-echo sequence (3D-SPGR) MRI was performed for all hips, and the presence of ONFH was determined by finding the area surrounded by the outer margin of the low-signal-intensity band on 3D-SPGR MRI. Patients with ONFH were categorized using the Steinberg, modified Kerboul, and JIC classification systems, and correlations among these three classification systems were investigated. Inter- and intraobserver reliability was assessed by 10 orthopaedic surgeons using 40 sets of 3D-SPGR MR images. The reliability of each system was evaluated using the kappa coefficient. The cumulative survival rate with collapse and undergoing hip arthroplasty as the endpoints was evaluated for each of the three classification systems (mean followup, 9 years; range, 2-16 years), and the association of higher grades within each classification and the risk of subsequent collapse were also evaluated., Results: We found strong correlations between the Steinberg and modified Kerboul classifications (ρ = 0.83, p < 0.001), the Steinberg and JIC classifications (ρ = 0.77, p < 0.001), and the modified Kerboul and JIC classifications (ρ = 0.80, p < 0.001). Interobserver reliability in the JIC classification (0.72; range, 0.30-0.90) was higher than that in the Steinberg classification (0.56; range, 0.24-0.84; p < 0.001) and the modified Kerboul classification (0.57; range, 0.35-0.80; p < 0.001). The cumulative survival rate with collapse as the endpoint after a minimum of 2 years of followup in the Steinberg classification differed between Grades A (82%; 95% confidence interval [CI], 66%-97%) and B (43%; 95% CI, 21.9%-64.8%; p = 0.007), Grades A and C (20%; 95% CI, 4.3%-35.7%; p < 0.001), and Grades B and C (p = 0.029). Survival was lower for modified Kerboul Grade 4 hips (12%; 95% CI, 0%-27.1%) than for Steinberg Grade C hips (20%; 95% CI, 4.3%-35.7%) and JIC Type C2 hips (18%; 95% CI, 2.8%-34.0%). The JIC classification was best able to identify hips at low risk of collapse because no JIC Type A hips collapsed., Conclusions: The JIC classification was more reliable and effective, at least for early-stage ONFH, than the Steinberg or modified Kerboul classifications. Further investigation might be useful to identify whether each classification system emphasizes specific risk factors for collapse., Level of Evidence: Level III, diagnostic study.