日本维持性血液透析患者蛋白质能量消耗的患病率和诊断标准评估

Background and Objectives: The International Society of Renal Nutrition and Metabolism (ISRNM) has recently recommended the use of the term “protein-energy wasting” (PEW). PEW is a state of malnutrition with decreased body stores of protein and energy fuel in hemodialysis patients and is known as a risk factor for morbidity and mortality. We examined the prevalence of PEW and the characteristics of PEW patients in a hemodialysis center in Japan. Methods and Study Design: Fifty-nine outpatients undergoing maintenance hemodialysis at Iga City General Hospital were evaluated. We observed their biochemical data, body composition, dietary intake, and the number of steps prospectively. PEW was defined according to ISRNM criteria. Results: Nine patients (15% of total) were diagnosed as having PEW. Among indicators of PEW criteria, the relevance ratios of “reduced muscle mass” and “unintentional low dietary energy intake” were significantly higher in PEW than in non-PEW. The number of steps was lower, and serum levels of glucose and C-reactive protein were higher in PEW. Conclusion: About 15% of Japanese hemodialysis patients are estimated to have PEW. Our results suggested that major contributing factors to PEW were reduced muscle mass, unintentional low dietary energy intake, lower amount of exercise, insulin resistance, and chronic inflammation.背景与目的：国际肾营养与代谢协会（ISRNM）最近推荐使用术语“蛋白质能量消耗（PEW）”。PEW 是血液透析患者体内蛋白质和能量储存减少的一种营养不良状态，并且被认为是患病率和死亡率的危险因素。我们在日本的一个血液透析中心研究了PEW 的患病率和PEW 患者的特征。方法与研究设计：我们评估了58 名在伊贺市综合医院做维持性血液透析的门诊患者，并观察了他们的生化数据、体成分、膳食摄入量和行走的步数。根据ISRNM 标准诊断PEW。结果：9 名（占总数的15%）患者被诊断为PEW。在PEW 诊断标准指标中，PEW 患者“肌肉量减少”和“无意识的低膳食能量摄入”的比例高于非PEW 患者。PEW 患者中行走的步数较低，而血清葡萄糖和C-反应蛋白水平较高。结论：约有15%的日本血液透析患者患有PEW。我们的研究结果表明：引起PEW 的主要因素是肌肉量减少、无意识的低膳食能量摄入、运动量低、胰岛素抵抗和慢性炎症

The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways

In vascular smooth muscle cells, large-conductance Ca2+-activated K+ channels (KCa channels) play a pivotal role in determining membrane potential, and thereby the vascular tone. Ginsenoside Re, a phytochemical from ginseng, is reported to activate this channel, but its precise mechanism is unsolved. Patch clamp studies showed that ginsenoside Re activates KCa channels in the arterial smooth muscle cell line A10 in a dose-dependent manner. The channel-opening effect of ginsenoside Re was inhibited by 1 μM L-NIO, an inhibitor of eNOS, but not by 3 μM SMTC, an inhibitor of nNOS, indicating that ginsenoside Re activated KCa channels through activation of eNOS. SH-6 (10 μM), an Akt inhibitor, and wortmannin, a PI3-kinase inhibitor, completely blocked activation of KCa channels by ginsenoside Re, indicating that it activates eNOS via a c-Src/PI3-kinase/ Akt-dependent mechanism. In addition, the ginsenoside Re-induced activation of eNOS and KCa channel was blocked by 10 μM ICI 182,780, an inhibitor of membrane estrogen receptor-α, suggesting that eNOS activation occurs via a non-genomic pathway of this receptor. In conclusion, ginsenoside Re releases NO via a membrane sex steroid receptors, resulting in KCa channel activation in vascular smooth muscle cells, promoting vasodilation and preventing severe arterial contraction

ガンカンジャサン ノ エイヨウ カンリ オ ササエル エイヨウ サポート チーム

Several hospitals have recently established a nutrition support team（NST）for the nutritional management of inpatients. The NST includes medical doctors, nurses, dietitians, and pharmacists. The aims of the NST are to improve the nutritional condition and the quality of life（QOL）of patients. In Tokushima University Hospital, a NST was established in２００２. Our team comprises physicians, surgeons, dentists, nurses, dietitians, pharmacists, dental hygienists, and physical therapists. Overall, ７０％ of patients undergoing a NST intervention have cancer. Nutritional management in patients with cancer plays an important role in the supportive care during cancer treatment（surgery, chemotherapy, and radiotherapy）. It is focused on the improvement of undernutrition, return to oral feeding, and an improvement in QOL in palliative care. Recently, cancer cachexia has received a lot of attention, with various studies reporting on the nutritional care in patients with cancer. Malnutrition negatively impacts a patient’s response to therapy, leading to an increase in the incidence of treatment-related side effects, and impairment in muscle function, performance status, immune function, and QOL. Recently, it has been reported that NST improves the treatment outcome in patients with cancer because nutritional status is an important part of cancer treatment. Therefore, nutritional management by a NST in patients with cancer has played a crucial role in cancer therapy

Hydrogen peroxide inhibits insulin-induced ATP-sensitive potassium channel activation independent of insulin signaling pathway in cultured vascular smooth muscle cells

Both reactive oxygen species (ROS) and insulin resistance have been reported to play essential pathophysiological roles in cardiovascular diseases, such as hypertension and atherosclerosis. However, the mechanistic link between ROS and insulin resistance in the vasculature remains unclear. Recently we have shown that insulin causes membrane hyperpolarization via ATP-sensitive potassium (KATP) channel activation, which is mediated by phosphatidylinositol 3-kinase (PI3-K) in cultured vascular smooth muscle cells (VSMCs). KATP channel in the vasculature is critical in the regulation of vascular tonus. Here we examined the effects of ROS induced by hydrogen peroxide (H2O2) on insulin-induced KATP channel activities in cultured VSMCs, A10 cells. H2O2 (10 μM) increased significantly intercellular ROS in A10 cells. By using a cell-attached patch clamp experiment, 10 μMH2O2 suppressed significantly insulin-induced KATP channel activation without inhibition of insulin receptor signal transduction component including IRS and Akt in A10 cells. Furthermore 10 μMH2O2 suppressed significantly pinacidil-induced KATP channel activation in A10 cells. These data suggest that H2O2might inhibit directly KATP channel independent of insulin signaling pathway. This study may contribute to our understanding of mechanisms of insulin resistance-associated cardiovascular disease

L-DOPA inhibits nitric oxide-dependent vasorelaxation via production of reactive oxygen species in rat aorta

Objectives : To clarify the underlying mechanisms of L-DOPA induced vasoconstriction in rat aorta. Methods : The effect of L-DOPA on phenylephrine-induced contractile force of blood vessels was examined in vitro using rat aortic ring preparations by isometric tension experiment. Involvement of nitric oxide (NO) in the effect of L-DOPA on vascular smooth muscle was studied by using Nω-Nitro-L-arginine (L-NNA), Sodium nitroprusside (SNP) in endothelium-intact and endothelium-denuded aortic rings. Results : L-DOPA potentiated α-adrenergic receptor- and depolarization-induced vascular contraction and inhibited acetylcholine-induced vasorelaxation. This effect was diminished by pretreatment of the aortic rings with L-NNA, an inhibitor of NO synthesis, or by removing the endothelium from the ring preparations. In endothelium-denuded rings, L-DOPA inhibited exogenous NO-dependent but not cGMP-mediated vasorelaxation. Increases in cGMP levels in response to an NO donor were attenuated by L-DOPA in cultured rat aortic smooth muscle cells. L-DOPA could not contract rings (without endothelium) pretreated with 3-(5’-hydroxymethyl- 2’-furyl)-1-benzyl indazole (YC-1), an activator of guanylyl cyclase, but SOD (150 U/ml) pretreatment of rings with endothelium inhibited contraction by L-DOPA. Conclusions : These results suggest that L-DOPA inhibits nitric-dependent vasorelaxation on vascular smooth muscle cells via production of reactive oxygen species

Development and Validation of Cutoff Value for Reduced Muscle Mass for GLIM Criteria in Patients with Gastrointestinal and Hepatobiliary–Pancreatic Cancers

The Global Leadership Initiative on Malnutrition (GLIM) criteria recommends using race- and sex-adjusted cutoff values for reduced muscle mass (RMM), but the only cutoff values available for Asians are the skeletal muscle mass index (SMI) established by the Asian Working Group for Sarcopenia (AWGS). This retrospective study aimed to develop and validate cutoff values for the fat-free mass index (FFMI) and arm circumference (AC) of Asians, and to investigate the association between GLIM malnutrition and prognosis. A total of 660 patients with primary gastrointestinal (GI) and hepatobiliary–pancreatic (HBP) cancers who underwent their first resection surgery were recruited and randomly divided into development and validation groups. The FFMI and AC cutoff values were calculated by receiver operating characteristic curve analysis for the AWGS SMI as the gold standard. The cutoff values for each RMM were used to diagnose malnutrition on the basis of GLIM criteria, and the survival rates were compared. The optimal FFMI cutoff values for RMM were 17 kg/m2 for men and 15 kg/m2 for women, and for AC were 27 cm for men and 25 cm for women. In the validation group, the accuracy of the FFMI and AC cutoff values to discriminate RMM were 85.2% and 68.8%, respectively. Using any of the three measures of RMM, overall survival rates were significantly lower in the GLIM malnutrition group. In conclusion, the cutoff values for the FFMI and AC in this study could discriminate RMM, and GLIM malnutrition using these cutoff values was associated with decreased survival

Impact of phase angle on postoperative prognosis

Objective Phase angle (PhA), by bioelectrical impedance analysis, has been used in patients with several diseases; however, its prognostic value in patients with gastrointestinal and hepatobiliary–pancreatic (HBP) cancer is unclear. The present study aimed to investigate the impact of PhA on postoperative short-term outcomes and long-term survival in these patients. Research Methods & Procedures This retrospective study reviewed data of 501 patients with gastrointestinal and HBP cancers who underwent first resection surgery and divided the data into the following groups according to the preoperative PhA quartile values by sex: high-PhA group with the highest quartile (Q4), normal-PhA group with middle quartiles (Q3 and Q2), and low-PhA group with the lowest quartile (Q1). Preoperative nutritional statuses, postoperative short-term outcomes during hospitalization, and 5-year survival between three groups were compared. Cox proportional hazard models were used to evaluate the prognostic effect of PhA. Results PhA positively correlated with body weight, skeletal muscle mass, and handgrip strength, and negatively correlated with age and C-reactive protein levels. The low-PhA group showed a high prevalence of malnutrition (48%) than normal-PhA (25%), and high-PhA (9%) (P < 0.001). The incidence of postoperative severe complications was 10% in all patients [14% in low-PhA, 12% in normal-PhA, and 4% in high-PhA (P = 0.018)]. The incidence of prolonged postoperative high care unit or/and intensive care unit stays was 8% in all patients [16% in low-PhA, 8% in normal-PhA, and 2% in high-PhA (P < 0.001)]. The 5-year survival rate was 74% in all patients [68% in low-PhA, 74% in normal-PhA, and 79% in high-PhA (P < 0.001)]. The multivariate analysis demonstrated that a low-PhA group was an independent risk factor for mortality (hazard ratio, 1.99; 95% confidence interval 1.05–3.90; P = 0.034). Conclusion PhA is a useful short-term and long-term postoperative prognostic marker for patients with gastrointestinal and HBP cancers

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

Muscle mass, quality, and strength; physical function and activity; and metabolic status in cachectic patients with head and neck cancer

Background & aims: Cancer cachexia is commonly associated with poor prognosis in patients with head and neck cancer (HNC). However, its pathophysiology and treatment are not well established. The current study aimed to assess the muscle mass/quality/strength, physical function and activity, resting energy expenditure (REE), and respiratory quotient (RQ) in cachectic patients with HNC. Methods: This prospective cross-sectional study analyzed 64 patients with HNC. Body composition was measured via direct segmental multifrequency bioelectrical impedance analysis, and muscle quality was assessed using echo intensity on ultrasonography images. Muscle strength was investigated utilizing handgrip strength and isometric knee extension force (IKEF). Physical function was evaluated using the 10-mwalking speed test and the five times sit-to-stand (5-STS) test. Physical activity was examined using a wearable triaxial accelerometer. REE and RQ were measured via indirect calorimetry. These parameters were compared between the cachectic and noncachectic groups. Results: In total, 23 (36%) patients were diagnosed with cachexia. The cachectic group had a significantly lower muscle mass than the noncachectic group. Nevertheless, there was no significant difference in terms of fat between the two groups. The cachectic group had a higher quadriceps echo intensity and a lower handgrip strength and IKEF than the noncachectic group. Moreover, they had a significantly slower normal and maximum walking speed and 5 STS speed. The number of steps, total activity time, and time of activity (<3 Mets) did not significantly differ between the two groups. The cachectic group had a shorter time of activity (≥3 Mets) than the noncachectic group. Furthermore, the cachectic group had a significantly higher REE/body weight and REE/fat free mass and a significantly lower RQ than the noncachectic group. Conclusions: The cachectic group had a lower muscle mass/quality/strength and physical function and activity and a higher REE than the noncachectic group. Thus, REE and physical activity should be evaluated to determine energy requirements. The RQ was lower in the cachectic group than that in the noncachectic group, indicating changes in energy substrate. Further studies must be conducted to examine effective nutritional and exercise interventions for patients with cancer cachexia

Infection risk in hemodialysis patient

Chronic care patients undergoing hemodialysis for treatment of end-stage renal failure experience higher rates of bloodstream-associated infection due to the patients' compromised immune system and management of the bloodstream through catheters. Staphylococcus species are a common cause of hemodialysis catheter-related bloodstream infections. We investigated environmental bacterial contamination of dialysis wards and contamination of hemodialysis devices to determine the source of bacteria for these infections. All bacterial samples were collected by the swab method and the agarose stamp method. And which bacterium were identified by BBL CRYSTAL Kit or 16s rRNA sequences. In our data, bacterial cell number of hemodialysis device was lower than environment of patient surrounds. But Staphylococcus spp. were found predominantly on the hemodialysis device (46.8%), especially on areas frequently touched by healthcare-workers (such as Touch screen). Among Staphylococcus spp., Staphylococcus epidermidis was most frequently observed (42.1% of Staphylococcus spp.), and more surprising, 48.2% of the Staphylococcus spp. indicated high resistance for methicillin. Our finding suggests that hemodialysis device highly contaminated with bloodstream infection associated bacteria. This study can be used as a source to assess the risk of contamination-related infection and to develop the cleaning system for the better prevention for bloodstream infections in patients with hemodialysis