Malnutrition by European Society for Clinical Nutrition and Metabolism criteria predicts prognosis in patients with gastrointestinal and hepatobiliary–pancreatic cancer

Background & Aims: The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed the ESPEN diagnostic criteria (EDC) for malnutrition in 2015. There is no report on the association between the EDC and prognosis in patients with gastrointestinal (GI) and hepatobiliary–pancreatic (HBP) cancer. This study aimed to (1) determine the prevalence of EDC malnutrition, (2) investigate the validity of the EDC as a nutritional and prognostic indicator, and (3) examine which components of the EDC are most related to long-term prognosis in patients with GI and HBP cancers. Methods: A total of 634 patients with primary GI and HBP cancers who underwent their first resection surgery between July 2014 and March 2018 were retrospectively recruited. According to the EDC, patients were divided into malnourished and non-malnourished groups. Clinical parameters and survival between these two groups were compared. The prognostic effects of the EDC and the EDC components were analyzed using Cox proportional hazard models. Results: The prevalence of EDC malnutrition was 22%. Anthropometric data and biochemical data were associated with EDC malnutrition. The 5-year survival rate was lower in the malnourished group (72%) than in the non-malnourished group (73%; P = 0.007). The multivariate analysis demonstrated that the malnourished group was an independent risk factor for mortality (hazard ratio = 1.70 in the malnourished group; 95% confidence interval 1.08–2.63; P = 0.024). Among EDC components, body mass index (BMI) of <18.5 kg/m2 was an independent poor prognostic factor. Conclusions: EDC malnutrition is associated with poor postoperative long-term prognosis. Among the EDC components, BMI of <18.5 kg/m2 is most associated with prognosis in patients with preoperative GI and HBP cancers

Coronary Artery Disease/Effects of Ablation on Cardiac Reserve

The effects of catheter ablation on exercise tolerance and quality of life in patients with atrial fibrillation (AF) have been reported. We assessed cardiac function in more detail using the leg positive pressure (LPP) technique and found that contractile reserve is particularly important in relation to exercise tolerance and prognosis. In this study, we used the LPP technique to examine changes in contractile reserve immediately after ablation and 6 months later. We prospectively enrolled patients who underwent catheter ablation for AF at 2 institutes. We performed LPP stress echocardiography 2 to 3 days after (FU-1) and 6 months after (FU-2) ablation to examine changes in cardiac function indexes. The primary end point was improvement in contractile reserve. Ultimately, 109 patients (mean age 67.4 ± 9.6 years; 70% men) underwent 2 sessions of LPP stress echocardiography. The median CHA2DS2-VASC score was 2 (interquartile range 13). From FU-1 to FU-2, the change in the stroke volume index after the LPP maneuver increased in patients with paroxysmal and persistent AF with low CHA2DS2-VASC scores (both p <0.05). Regardless of AF subtype, contractile reserve at FU-2 improved in patients with low CHA2DS2-VASC scores compared with that at FU-1. In contrast, patients with high CHA2DS2-VASC scores had no change. In conclusion, patients with AF with a low CHA2DS2-VASC score had improved contractile reserve after ablation, whereas patients with high scores did not show any improvement. Aggressive interventions in patients with high scores may lead to better management after catheter ablation

A Report on Overseas Teaching Practicum by Graduate Students in Elementary/Secondary Schools in the United States（Ⅺ）

This paper reports on the 11th overseas teaching practicum in the U.S. 12 students joined this year’s program and they observed and conducted lessons in English in three local public schools in North Carolina after careful and repeated preparation sessions in Japan. Many of them did lessons on crosscultural understandings and a few taught subject contents. Through the trail to convey messages in English, their foreign language, students learned the role of verbal and nonverbal language and the more universal way to explain topics to children who are unfamiliar with what re taught. And they also learned and noticed the cultural differences and similalities between the two countries. It seemed that students realized that the two countries share many things in common such as what chidren are like, teachers’ attitude toward children and challenges they are facing, and people’s kindness. These learning was no substitute experience for the participants and it is hoped that their experience will be passed to the next generation when they become teachers

Microbleed clustering in thalamus sign in CADASIL patients with NOTCH3 R75P mutation

Background and objectiveCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microvascular disease characterized by the development of vascular dementia and lacunar infarctions. This study aimed to identify the genetic and clinical features of CADASIL in Japan.MethodsWe conducted genetic analysis on a case series of patients clinically diagnosed with CADASIL. Clinical and imaging analyses were performed on 32 patients with pathogenic mutations in the NOTCH3 gene. To assess the presence of cerebral microbleeds (CMBs), we utilized several established rating scales including the Fazekas scale, Scheltens rating scale, and Microbleed Anatomical Rating Scale, based on brain MRI images.ResultsAmong the 32 CADASIL patients, 24 cases were found carrying the R75P mutation in NOTCH3, whereas the remaining eight cases had other NOTCH3 mutations (R75Q, R110C, C134F, C144F, R169C, and R607C). The haplotype analysis of the R75P mutation uncovered the presence of a founder effect. A brain MRI analysis revealed that cases with the R75P mutation had a significantly higher total number of CMBs, particularly in the thalamus when compared to patients with other NOTCH3 mutations. Among 15 out of 24 cases with the R75P mutation, we observed a notable clustering of CMBs in the thalamus, termed microbleed clustering in thalamus sign (MCT sign).ConclusionWe propose that the MCT sign observed in NOTCH3 R75P-related CADASIL patients may serve as a potentially characteristic imaging feature. This finding offers further insights into the interactions between genotypes and phenotypes between NOTCH3 and CADASIL

Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia

Yanagiya R., Miyatake Y., Watanabe N., et al. Amino acid influx via LAT1 regulates iron demand and sensitivity to PPMX-T003 of aggressive natural killer cell leukemia. Leukemia , (2024); 10.1038/s41375-024-02296-6.Aggressive natural killer cell leukemia (ANKL) is a rare hematological malignancy with a fulminant clinical course. Our previous study revealed that ANKL cells proliferate predominantly in the liver sinusoids and strongly depend on transferrin supplementation. In addition, we demonstrated that liver-resident ANKL cells are sensitive to PPMX-T003, an anti-human transferrin receptor 1 inhibitory antibody, whereas spleen-resident ANKL cells are resistant to transferrin receptor 1 inhibition. However, the microenvironmental factors that regulate the iron dependency of ANKL cells remain unclear. In this study, we first revealed that the anti-neoplastic effect of PPMX-T003 was characterized by DNA double-strand breaks in a DNA replication-dependent manner, similar to conventional cytotoxic agents. We also found that the influx of extracellular amino acids via LAT1 stimulated sensitivity to PPMX-T003. Taken together, we discovered that the amount of extracellular amino acid influx through LAT1 was the key environmental factor determining the iron dependency of ANKL cells via adjustment of their mTOR/Myc activity, which provides a good explanation for the different sensitivity to PPMX-T003 between liver- and spleen-resident ANKL cells, as the liver sinusoid contains abundant amino acids absorbed from the gut. (Figure presented.

学生のアルバイト職場における労働安全衛生

健康管理という観点から学生アルバイト職場の労働安全衛生について調査した。調査は無記名の質問紙で、アルバイト就労状況、経済的な背景、アルバイト職場でのトラブル経験、アルバイトと学業や睡眠、労働法規の認知度、相談先についての質問とした。多くの学生がアルバイトに従事していた。様々なトラブルを多くの学生が経験しており、アルバイトをする限り何らかのトラブルに遭遇する可能性が高いということが示された。そのため、身体的、あるいは精神的にストレスがかかっていたり、睡眠不足となるなど労働安全衛生上の問題があった。しかし、経済的理由で辞めることができないとする学生が多かった。大学で可能な対策もあるが、大学のみでは学生のアルバイト職場での労働安全衛生環境を整えることはできない。学費・奨学金制度のほか、非正規雇用の拡大など、学生に大きな負担をかけている制度や社会の見直しが必要である。We conducted a survey of occupational safety and health at part time job among students of Nayoro City University in 2015. Among respondent students,73% had experience working part-time since admission to university. A sizable percentage of students have experienced a variety of psychological harassments and troubles at work. As a consequence, these students have suffered mental physical stress, and sustained sleep deprivation. Nevertheless, they indicated that it was impossible to quit their jobs because difficulties covering their tuition fees and living expenses. This survey revealed that safety and health at part-time jobs is a significant issue in the healthcare of university students. Health service centers in universities are not able to resolve these issues alone. Japanese social systems and practices that place excessive strain on university students, such as expensive academic fees, heavy student loans and an growing irregular employment system, need to be reconsidered and strategies for improvement discussed by those in positions to implement change

Ossiculoplasty for Malleus Bar with Incudostapedial Disconnection and Fused Incudomalleolar Joint

Malleus bar is an abnormal bony connection between the malleus handle and the posterior wall of the tympanic cavity. We report a patient with a malleus bar and another malformation of the ossicles. An 11-year-old boy presented with hearing impairment since early childhood. Computed tomography (CT) revealed a malleus bar with an incudostapedial disconnection in the right ear. At tympanoplasty, the malleus bar was first identified and removed. A fused malleus-incus, not visible on the preoperative CT, was found intraoperatively. Therefore, the fused malleus-incus was removed; then, the ossicular chain was reconstructed, resulting in an improved postoperative hearing level. On preoperative CT, the disconnected incudostapedial joint had been identified, whereas the fused malleus-incus had not. Given the variations in the malleus bar anomaly of the middle ear, the surgical procedure for ossiculoplasty should be adapted intraoperatively based on any findings not visible on the preoperative CT

Controlling bleeding during uniportal thoracoscopic major pulmonary resection

Aim: In uniportal thoracoscopic major pulmonary resection, it is important to appropriately manage significant vessel injury, to ensure patient safety and minimize conversion to thoracotomy. We analyzed cases of significant vessel injury and investigated efficacy of an algorithm to manage bleeding during thoracoscopic uniportal major pulmonary resection.Methods: A total of 169 patients underwent “uniportal thoracoscopic major pulmonary resection” (lobectomy or segmentectomy) at our department between February 2019 and April 2021. These patients were classified into groups with (group A, n = 8) and without (group B, n = 161) intraoperative massive bleeding. Patient characteristics and perioperative results were compared between the two groups. Patients with significant vessel injury and conversion to thoracotomy were analyzed in detail.Results: Group B had significantly less blood loss (A: 197 ± 173 g; B: 42 ± 74 g, P &lt; 0.0001) and shorter-duration postoperative drainage (A: 2.6 ± 1.8 days; B: 1.6 ± 1.3 days, P = 0.036). There were no group differences in any other factors. The most frequently injured vessel in group A was the pulmonary artery (75%). Emergent conversion was required in four cases (cases 7, 76, 128, and 133; 2.4%) due to intraoperative bleeding. No patient developed catastrophic bleeding or required an intraoperative transfusion.Conclusion: We managed significant vessel injury appropriately during uniportal thoracoscopic major pulmonary resection using the troubleshooting algorithm. The algorithm for the uniportal approach was considered effective and easy to apply even by less-experienced surgeons