Excess Vitamins or Imbalance of Folic Acid and Choline in the Gestational Diet Alter the Gut Microbiota and Obesogenic Effects in Wistar Rat Offspring

Excess vitamin intake during pregnancy leads to obesogenic phenotypes, and folic acid accounts for many of these effects in male, but not in female, offspring. These outcomes may be modulated by another methyl nutrient choline and attributed to the gut microbiota. Pregnant Wistar rats were fed an AIN-93G diet with recommended vitamin (RV), high 10-fold multivitamin (HV), high 10-fold folic acid with recommended choline (HFol) or high 10-fold folic acid without choline (HFol-C) content. Male and female offspring were weaned to a high-fat RV diet for 12 weeks post-weaning. Removing choline from the HFol gestational diet resulted in obesogenic phenotypes that resembled more closely to HV in male and female offspring with higher body weight, food intake, glucose response to a glucose load and body fat percentage with altered activity, concentrations of short-chain fatty acids and gut microbiota composition. Gestational diet and sex of the offspring predicted the gut microbiota differences. Differentially abundant microbes may be important contributors to obesogenic outcomes across diet and sex. In conclusion, a gestational diet high in vitamins or imbalanced folic acid and choline content contributes to the gut microbiota alterations consistent with the obesogenic phenotypes of in male and female offspring.     

A Korean-Style Balanced Diet Has a Potential Connection with Ruminococcaceae Enterotype and Reduction of Metabolic Syndrome Incidence in Korean Adults

Metabolic syndrome is associated with usual dietary patterns that may be involved in enterotypes. We aimed to understand the potential relationship of enterotypes and dietary patterns to influence metabolic syndrome in the Koreans. Using the Korea National Health and Nutrition Examination Survey (KNHANES)-VI in 2014, metabolic parameters were also analyzed among the dietary patterns classified by principal component analysis in Korean adults. The fecal microbiota data of 1199 Korean adults collected in 2014 were obtained from the Korea Centers for Disease Control and Prevention. Enterotypes were classified based on Dirichlet multinomial mixtures (DMM) by Mothur v.1.36. The functional abundance of fecal bacteria was analyzed using the PICRUSt2 pipeline. Korean adults were clustered into three dietary patterns including Korean-style balanced diets (KBD, 20.4%), rice-based diets (RBD, 17.2%), and Western-style diets (WSD, 62.4%) in KNHANES. The incidence of metabolic syndrome was lowered in the order of RBD, WSD, and KBD. The participants having a KBD had lower serum C-reactive protein and triglyceride concentrations than those with RBD and WSD (p < 0.05). Three types of fecal bacteria were classified as Ruminococcaceae type (ET-R, 28.7%), Prevotella type (ET-P, 52.2%), and Bacteroides type (ET-B, 42.1%; p < 0.05). ET-P had a higher abundance of Prevotella copri, while ET-R contained a higher abundance of Alistipes, Akkermansia muciniphila, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. ET-B had a higher abundance of the order Bilophila (p < 0.05). Metabolism of propanoate, starch, and sucrose in fecal microbiome was higher in ET-P and ET-R, whereas fatty acid metabolism was enhanced in ET-B. Fecal microbiota in ET-P and ET-B had higher lipopolysaccharide biosynthesis activity than that in ET-R. The metabolic results of KBD and RBD were consistent with ET-R and ET-P’s gut microbiota metabolism, respectively. In conclusion, Korean enterotypes of ET-P, ET-B, and ET-R were associated with RBD, WSD, and KBD, respectively. This study suggests a potential link between dietary patterns, metabolic syndrome, and enterotypes among Korean adults.     

Common Pitfalls in the Management of Patients with Micronutrient Deficiency: Keep in Mind the Stomach

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.     

Prolonged Isolated Soluble Dietary Fibre Supplementation in Overweight and Obese Patients: A Systematic Review with Meta-Analysis of Randomised Controlled Trials

The prevalence of overweight and obesity is rising rapidly, currently affecting 1.9 billion adults worldwide. Prebiotic dietary fibre supplementation is a promising approach to improve weight loss and reduce metabolic complications in overweight and obese subjects due to modifications of the microbiota composition and function. Previous systematic reviews and meta-analyses addressing similar questions revealed discordant evidence and/or are outdated. We searched MEDLINE, Embase, Google Scholar, and forward and backward citations for randomised controlled trials (RCTs) with isolated soluble dietary fibre supplementation for at least 12 weeks in overweight and obese patients measuring body weight, published through April 2022. We expressed the results as mean differences (MDs) using the random-effects model of the metafor package in R and assessed risk of bias using the Cochrane RoB2 tool. We conducted the study according to the PRISMA guidelines and registered the protocol on PROSPERO (CRD42022295246). The participants with dietary fibre supplementation showed a significantly higher reduction in body weight (MD −1.25 kg, 95% CI −2.24, −0.25; 27 RCTs; 1428 participants) accompanied by a significant decrease in BMI, waist circumference, fasting blood insulin, and HOMA-IR compared to the control group. Certainty of evidence was high, paving the way for the implementation of isolated soluble dietary fibre supplementation into clinical practice.     

Possible Reduction of Cardiac Risk after Supplementation with Epigallocatechin Gallate and Increase of Ketone Bodies in the Blood in Patients with Multiple Sclerosis. A Pilot Study

Multiple sclerosis (MS) is a neurodegenerative disease that causes anthropometric changes characterised by functional disability, increase in fat mass, and decrease in lean mass. All these variables are related to a greater cardiac risk. The polyphenol epigallocatechin gallate (EGCG) and an increase in ketone bodies in the blood have been shown to have beneficial effects on anthropometric and biochemical variables related to cardiovascular activity. The aim of this study was to analyse the impact of the intervention with EGCG and ketone bodies on cardiac risk in MS patients. A population of 51 MS patients were randomly assigned to a control group and an intervention group (daily dose of 800 mg of EGCG and 60 mL of coconut oil). Both groups followed an isocaloric diet for 4 months. Levels of beta-hydroxybutyrate (BHB), albumin, paraoxonase 1 (PON1) and C-reactive protein (CRP) were measured in serum before and after the intervention, as well as determining functional ability, waist circumference, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), fat percentage and muscle percentage. After 4 months, in the intervention group there was a significant increase in BHB, PON1 and albumin, while CRP did not vary; a significant decrease in cardiac risk associated with a significant decline in WHR; as well as a significant increase in muscle percentage. By contrast, these changes were not observed in the control group. Finally, results from analysis of variance (ANOVA) revealed a significant time–condition interaction effect, observing that WHtR and fat mass decreased in the intervention group, while they increased in the control group.     

Effects of Supplementation with the Fat-Soluble Vitamins E and D on Fasting Flow-Mediated Vasodilation in Adults: A Meta-Analysis of Randomized Controlled Trials

The effects of fat-soluble vitamin supplementation on cardiovascular disease (CVD) risk are not clear. Therefore, we performed a meta-analysis to quantify effects of fat-soluble vitamin supplements on fasting flow-mediated vasodilation (FMD) of the brachial artery, a validated marker to assess CVD risk. Randomized placebo-controlled trials (RCTs) were identified by a systematic search till July 2014. Seven RCTs studying the effects of vitamin E supplements (range: 300 to 1800 IU per day) and nine RCTs examining the effects of vitamin D supplements, that involved, respectively, 303 and 658 adults, were included. No studies with carotenoid or vitamin K supplements were found. Vitamin E supplementation increased FMD vs. control by 2.42% (95% CI: 0.46% to 4.37%; p = 0.015). No effects of vitamin D supplementation were found (0.15%; 95% CI: −0.21% to 0.51%; p = 0.41). These effects did not depend on subject characteristics, treatment characteristics or technical aspects of the FMD measurement. However, no dose-response relationship was evident for vitamin E, statistical significance depended on one study, while the levels of supplement were far above recommended intakes. The current meta-analysis, therefore, does not provide unambiguous evidence to support the use of fat-soluble vitamin supplements to improve fasting FMD in adults.     

Effects of Selenium Supplementation in Patients with Mild Cognitive Impairment or Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Elevated levels of oxidative stress could cause and aggravate Alzheimer’s disease (AD). Selenium (Se) is a trace element with antioxidant and anti-inflammatory activity with neuroprotective effects. To evaluate the effects of Se supplementation in patients with AD or mild cognitive impairment (MCI) through a systematic review and meta-analysis, data were searched and collected from four electronic databases, including clinical trial studies published until December 2020, following the PRISMA guidelines. Statistical analysis was performed by RevMan, and the risk of bias was assessed using the Rob 2 tool. A total of 1350 scientific papers were collected, and following evaluation 11 papers were included in the systematic review and 6 of these were used in the meta-analysis. Studies that evaluated only Se supplementation observed an improvement in Se levels, glutathione peroxidase (GPX) activity, and in some cognitive tests in MCI patients; similarly, improvement in Se levels and mini-mental score was also observed in AD patients. Regarding supplementation of Se plus other nutrients, improvement in cognitive tests was observed in both AD and MCI patients. Therefore, Se supplementation is a good alternative for patients with AD and MCI for improving Se levels and GPX activity. More detailed studies are required to further evaluate the effects of Se on the cognitive deficit and oxidative stress associated with AD and MCI.     

Effect of Intradialytic Oral Nutritional Supplementation with or without Exercise Improves Muscle Mass Quality and Physical Function in Hemodialysis Patients: A Pilot Study

Background: Oral nutritional supplementation (ONS) with or without exercise (EX) could improve muscle mass (MM) in chronic kidney disease. Methods: Patients were randomized into two groups: (1) ONS and (2) ONS + EX. Thigh muscle area (cm²) and intramuscular lipid content via attenuation were evaluated at baseline and 6 months with computed tomography (CT) to measure MM quantity and quality. Physical function was measured by six-minute walk test (6 MWT), gait speed, handgrip strength (HGS), and Time Up and Go test (TUG) at baseline and 3 and 6 months. Results: The ONS group (n= 14) showed statistically significant improvement in gait speed and HGS; ONS + EX group (n = 10) showed differences in gait speed, in 6 MWT, and HGS. In the ANOVA (3 times × 2 groups), no differences were observed between groups. Greater effect sizes in favor to ONS + EX group were observed in the 6 MWT (d = 1.02) and TUG test (d = 0.63). Muscle quality at six months revealed a significant trend in favor of the EX-group (p = 0.054). Conclusions: Both groups had improved physical function, and greater effect sizes were seen in the ONS + EX group for the 6 MWT and TUG test. Neither MM quantity or quality was improved in either group.     

Estimating the Costs of Therapy in Patients with Relapsed and/or Refractory Multiple Myeloma: A Model Framework

Background

Multiple myeloma is a progressive cancer for which there is no cure. Despite treatment, almost all patients eventually experience periods of disease relapse and remission. With the increasing use of novel therapies, including bortezomib, lenalidomide, carfilzomib, pomalidomide, and panobinostat, benchmarks for assessing the value of these therapies in treating patients with relapsed or refractory multiple myeloma (RRMM) are needed for physicians and payers alike.

Objectives

To develop a model framework and to calculate an annual estimate of the total costs per patient for the treatment of patients with RRMM using 7 common treatment regimens, including bortezomib plus dexamethasone; panobinostat, bortezomib, and dexamethasone; lenalidomide plus dexamethasone; lenalidomide, bortezomib, and dexamethasone; carfilzomib; carfilzomib, lenalidomide, and dexamethasone; and pomalidomide plus dexamethasone.

Methods

The expenditures for drugs and their administration, for prophylaxis and adverse event monitoring, and for the treatment of grade 3 or 4 adverse events were included in the calculations of the total pharmacy and medical costs. The drug costs were based on published pricing and labeled dosing schedules; the adverse event prophylaxis and monitoring costs were obtained from peer-reviewed publications; and the adverse event incidence rates were obtained from each regimen''s prescribing information and from clinical trials. All the costs were summed over the duration of therapy for which the drugs were administered and were calculated separately for commercial and Medicare plans. The duration of therapy for each regimen was the time for which a patient had to be receiving the regimen to obtain 12 months of progression-free survival based on the duration-of-therapy to progression-free survival ratio observed from published clinical trials and/or the drug''s labeling.

Results

The pharmacy costs were highest for pomalidomide plus dexamethasone, whereas the medical costs were highest for the combination of carfilzomib, lenalidomide, and dexamethasone. The total cost associated with available treatments for RRMM was highest for regimens that included lenalidomide (approximate range, $126,000-$256,000). Only bortezomib plus dexamethasone and the combination of panobinostat, bortezomib, and dexamethasone had total costs that were lower than $125,000 per patient.

Conclusion

This study represents the first model developed to comprehensively estimate the costs of managing RRMM with all currently approved and guideline-recommended regimens in the United States. As such, it provides the framework and basis for further budget impact analyses and for cost-effectiveness comparisons with these regimens.     

Coleus forskohlii Extract Supplementation in Conjunction with a Hypocaloric Diet Reduces the Risk Factors of Metabolic Syndrome in Overweight and Obese Subjects: A Randomized Controlled Trial

Limited studies have shown that Coleus forskohlii extract may aid in weight management. This randomized, double blind placebo-controlled clinical study assessed the effects of supplementation with C. forskohlii extract on key markers of obesity and metabolic parameters in overweight and obese individuals. Thirty participants completed the trial and they were randomly assigned to receive either 250 mg of C. forskohlii extract (n = 15) or a placebo twice daily for 12 weeks. All participants were advised to follow a hypocaloric diet throughout the study. Body weight, body mass index (BMI), waist and hip circumference, and waist to hip ratio, were monitored fortnightly. Dietary intake was assessed at the baseline and weeks 4, 8 and 12. Appetite was assessed using visual analogue scales and blood samples were analyzed for plasma lipids, ghrelin, leptin, glucose and insulin at the baseline and end of the intervention. Significant reductions to waist and hip circumference (p = 0.02; p = 0.01, respectively) were recorded in both experimental and placebo groups after the 12 week intervention. Furthermore, high density lipoprotein-cholesterol (HDL-C) was significantly increased (p = 0.01) in both groups. The experimental group showed a favorable improvement in insulin concentration and insulin resistance (p = 0.001; 0.01 respectively) compared to the placebo group. These findings suggest that C. forskohlii extract in conjunction with a hypocaloric diet may be useful in the management of metabolic risk factors.     

Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting

Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m²; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.     

Potential Benefits of the Mediterranean Diet and Physical Activity in Patients with Hidradenitis Suppurativa: A Cross-Sectional Study in a Spanish Population

There is scarce scientific information regarding the potential benefits of healthy lifestyles in patients with hidradenitis suppurativa (HS). The objective of this study is to explore the potential association between the adherence to a Mediterranean diet (MD), physical activity and HS severity. A cross-sectional study that included patients with HS was conducted. Disease severity was evaluated by the International Hidradenitis Suppurativa Severity Score System (IHS4) and self-reported disease activity using a Numeric Rating Scale (NRS, 0–10). The adherence to a MD was assessed by the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire and the level of physical activity by the International Physical Activity questionnaire. A total of 221 patients with HS were included in our study. The adherence to a MD was average for a Spanish population. A higher adherence to a MD was associated with lower disease activity, lower self-reported Hurley and lower IHS4. The use of extra virgin olive oil as the main culinary lipid was the dietary habit that implied a lower degree of disease activity (p < 0.05). Regarding physical activity, both the self-reported severity and IHS4 presented an inverse association with the intensity of physical activity. The adherence to a MD and the intensity of physical activity were positively associated. The Mediterranean dietary pattern may have an impact on HS. Greater adherence to a MD is related to lower HS severity and more physical activity also correlates to lower disease severity. The MD could be an appropriate dietary pattern for patients with HS due to its anti-inflammatory properties, and combining this with increased levels of physical activity could have additional benefits.     

对苯二甲酸、乙二醇、联苯-联苯醚联合作用对肝脏损伤的实验研究

为研究对苯二甲酸 (TPA)、乙二醇 (EG)、联苯 联苯醚 (DOW)对大鼠肝脏损伤的联合作用及其损伤机制 ,采用亚慢性动物实验 ,利用三因素两水平析因设计方法 ,分析研究了反映大鼠肝脏损伤的酶学、生化和形态学指标。结果表明 ,TPA、EG、DOW各联合染毒组大鼠的血清ALT活性和血清总胆汁酸 (TBA)含量 ,与单剂量染毒组及对照组相比均有不同程度的增高 ,析因分析结果提示 ,此 3种物质对肝脏损伤的联合作用特征表现为相加 (TPA +EG)、协同 (EG +DOW)、协同 (TPA +DOW)和相加作用 (TPA +EG +DOW) ,并通过形态学观察进一步得到验证。     

Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study

The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. −0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.     

Whether or Not the Effects of Curcuma longa Supplementation Are Associated with Physical Exercises in T1DM and T2DM: A Systematic Review

Diabetes mellitus is one of the most prevalent chronic diseases in the world; one of its main characteristics is chronic hyperglycemia. Pharmacotherapy and other alternatives such as regular exercise are among the therapeutic methods used to control this pathology and participate in glycemic control, as well as the ingestion of plant extracts with antioxidant effects. Among the different plants used for this purpose, curcumin has potential to be used to attenuate the hyperglycemic condition triggered by diabetes mellitus (DM). Some prior studies suggest that this plant has antioxidant and hypoglycemic potential. This review aims to evaluate the antioxidant and hypoglycemic potential of curcumin supplementation in Type 1 DM (T1DM) and Type 2 DM (T2DM). The search considered articles published between 2010 and 2019 in English and Portuguese, and a theoretical survey of relevant information was conducted in the main databases of scientific publications, including the Virtual Health Library and its indexed databases, PubMed, LILACS (Latin American and Caribbean Literature on Health Sciences—Health Information for Latin America and the Caribbean—BIREME/PAHO/WHO), and Scientific Electronic Library Online (SciELO). The associated use of turmeric and physical exercise has demonstrated antioxidant, anti-inflammatory, and hypoglycemic effects, suggesting that these could be used as potential therapeutic methods to improve the quality of life and survival of diabetic patients.     

Effects of a Lacto-Ovo-Vegetarian Diet on the Plasma Lipidome and Its Association with Atherosclerotic Burden in Patients with Coronary Artery Disease—A Randomized,Open-Label,Cross-over Study

A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain polyunsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.     

Investigation of the Effect of Nutritional Supplementation with Whey Protein and Vitamin D on Muscle Mass and Muscle Quality in Subacute Post-Stroke Rehabilitation Patients: A Randomized,Single-Blinded,Placebo-Controlled Trial

In post-stroke hemiparesis patients, the skeletal muscle mass decrease rapidly with the histological degradation. We investigated the effect of nutritional supplementation with whey protein and vitamin D on the muscle mass and muscle quality, in post-stroke convalescent rehabilitation patients in a randomized, single-blinded, placebo-controlled trial. Fifty patients were randomly assigned to two groups; HP group received supplemental jelly (100 kcal; whey protein 10 g; vitamin D 20 μg) twice a day throughout up to 16-week period, the control group received placebo jelly. Cross-sectional area (CSA) of thigh muscle, skeletal muscle index (SMI), muscle strength, activity of daily living (ADL), and some nutritional indicators in blood were measured. Although no significant difference was observed in CSA and SMI between the groups, fat infiltration into the thighs muscle was singnificantly lower in the HP group. There were no significant difference in muscle strength and ADL between the groups. Blood urea nitrogen and serum 25(OH)D at endpoint were significantly higher in the HP group but physiological normal ranges. Supplementation with whey protein and vitamin D in post-stroke patients led to suppression of fat infiltration into the muscle. Long-term follow-up studies are needed to verify whether this nutritional intervention provides substantial benefits for the prognosis of stroke survivors.     

致突变剂敏感性与头颈肿瘤患者放化疗后第二原发肿瘤发生风险的研究

目的 探讨基因稳定性与头颈肿瘤患者放化疗后发生第二原发肿瘤(secondary primary tumor,SPT)的关系。方法 SPT组和无SPT组入组病例分别为67、47例,正常对照组40例。以博莱霉素作为致突变剂,分析既往有头颈肿瘤放疗±化疗史、发生和未发生SPT者,分析外周血淋巴细胞平均染色单体断裂数。结果 从初诊头颈肿瘤的年龄开始,SPT组至发生SPT的时间、无SPT组至最后随访时间分别为16.73 ±6.31(95% CI,15.19~18.27)和18.51 ±8.51(95% CI,16.01~21.01)年(F=1.643,P=0.203)。发生SPT的部位主要是头颈部,病理类型以鳞癌居多。SPT组、无SPT组和对照组外周血淋巴细胞平均染色单体断裂数分别为0.88 ±0.29(95% CI,0.81~0.95)、0.56 ±0.19(95% CI,0.50~0.61)和0.52 ±0.18(95% CI,0.46~0.58)个,差异有统计学意义(F=6.519,P=0.002)。以 ≥ 0.5个断裂数/细胞作为博莱霉素敏感性高低的分界点,3组对博莱霉素敏感的百分比分别为85.07%、65.96%、52.50%,差异有统计学意义(χ²=13.611,P=0.000)。将SPT组设置为病例组,余为对照组,外周血淋巴细胞平均染色单体断裂数的ROC曲线下面积为0.829,标准误是0.037(P=0.000),该值为0.69时特异性和敏感性均较高。结论 头颈肿瘤患者潜在的基因不稳定性与SPT密切相关;发生SPT的潜伏期较长,超过10年;外周血淋巴细胞平均染色单体断裂数判断该患者人群发生SPT的风险有价值, ≥ 0.69可以作为高危SPT的最佳阈值,但需要进一步验证。