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Gut microbiota responses to complementary food sources differ by milk feeding type. 肠道菌群对辅食来源的反应因牛奶喂养类型而异。
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-28 DOI: 10.1016/j.clnu.2026.106587
B M Perrett, K Miliku, T J Moraes, E Simons, P Mandhane, M Kebbe

Background & aims: Early-life nutrition shapes host-microbe interactions with lasting consequences for health. While dietary patterns are known to influence the infant gut microbiome, the impact of solid food source (homemade, commercial, or mixed) has not been examined. Our aims were to determine how solid food source at 6 months relates to infant gut microbiome diversity and composition at 1 year, and whether relationships differ by milk feeding type..

Methods: We conducted a secondary analysis within the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Solid food source was assessed at 6 months, and stool samples at 1 year were profiled using 16S rRNA sequencing. Generalized linear models were used to assess alpha-diversity; permutational multivariate analysis of variance (PERMANOVA) was used to evaluate beta-diversity based on OTU-level Bray-Curtis dissimilarities; and Microbiome Multivariate Association with Linear Models 2 (MaAsLin2), using centered log-ratio normalization, was used to examine taxa-level associations, adjusting for relevant perinatal and dietary covariates. Effect modification by milk feeding type (human milk, formula, combination, or weaned) at 6 months and 1 year was examined. Benjamini-Hochberg correction was applied (p < 0.05; q < 0.25).

Results: A total of 368 infants were included. At 6 months, most were mixed-fed (n = 154; 41.8 %), followed by homemade-fed (n = 143; 38.9 %) and commercially-fed (n = 71; 19.3 %). Solid food source explained only 0.53 % of gut microbiota variability. Differences were most pronounced in formula-fed infants: at 6 months, those given homemade or mixed foods showed higher abundances of Firmicutes, Turicibacteraceae, and Turicibacter compared with commercially fed infants. Within this group, mixed feeding was further linked to higher Eubacteriaceae and Lachnospiraceae (all q < 0.25). At 1 year, formula-fed infants who received homemade foods had higher microbial diversity (p = 0.028) but lower Shannon diversity (p = 0.041) than those receiving commercial foods, suggesting shifts in both community richness and evenness. No significant differences in gut microbiome diversity and composition were observed in the overall cohort or among infants receiving human milk or fully weaned (q > 0.25).

Conclusions: Solid food source is a previously under-investigated driver of infant microbiome variability, with effects contingent on milk feeding. Human milk may buffer against dietary choices, whereas formula-fed infants show heightened sensitivity to complementary food source, informing precision nutrition in early life.

背景与目的:生命早期的营养形成宿主与微生物的相互作用,并对健康产生持久的影响。虽然已知饮食模式会影响婴儿肠道微生物群,但固体食物来源(自制、商业或混合)的影响尚未得到研究。我们的目的是确定6个月时的固体食物来源与1岁时婴儿肠道微生物群多样性和组成的关系,以及这种关系是否因母乳喂养类型而不同。方法:我们在加拿大健康婴儿纵向发育(CHILD)队列中进行了二次分析。6个月时评估固体食物来源,1岁时使用16S rRNA测序对粪便样本进行分析。采用广义线性模型评估α多样性;基于otu水平的Bray-Curtis差异,采用排列多元方差分析(peromova)评价beta多样性;和微生物组多变量线性关联模型2 (MaAsLin2),采用中心对数比归一化,在调整了相关的围产期和饮食协变量后,用于检查类群水平的关联。研究了6个月和1岁时不同喂养方式(人乳、配方奶、组合奶或断奶奶)对效果的影响。采用Benjamini-Hochberg校正(p < 0.05; q < 0.25)。结果:共纳入368例婴儿。6个月时,大多数是混合饲养(n = 154, 41.8%),其次是家养饲养(n = 143, 38.9%)和商业饲养(n = 71, 19.3%)。固体食物来源只能解释0.53%的肠道菌群变异。在配方奶粉喂养的婴儿中,差异最为明显:在6个月时,与商业喂养的婴儿相比,那些吃自制或混合食物的婴儿显示出更高的厚壁菌门、Turicibacteraceae和Turicibacter的丰度。在该组中,混合饲养进一步增加了真杆菌科和毛缕菌科(均q < 0.25)。在1岁时,食用自制食品的婴儿的微生物多样性高于食用商业食品的婴儿(p = 0.028),但香农多样性低于食用商业食品的婴儿(p = 0.041),这表明群落丰富度和均匀度发生了变化。在整个队列中,在接受母乳喂养或完全断奶的婴儿中,肠道微生物群的多样性和组成没有显著差异(q > 0.25)。结论:固体食物来源是先前未被充分研究的婴儿微生物组变异性驱动因素,其影响取决于母乳喂养。母乳可以缓冲饮食选择,而配方奶喂养的婴儿对辅食来源表现出更高的敏感性,从而在生命早期提供精确营养。
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引用次数: 0
Proof of concept for an age- and inflammation-adjusted model for the establishment of pediatric serum copper reference intervals. 建立儿童血清铜参考区间的年龄和炎症调整模型的概念证明。
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-25 DOI: 10.1016/j.clnu.2026.106586
Helena Rodriguez-Gonzalez, Angela Arias, Elisabet Poyatos, Mariela Mercedes de Los Santos, Beatriz Minguez, Silvia Meavilla, Camila Garcia-Volpe, Ines Loverdos, Cristina Molera, Mercedes Casado, Aida Ormazabal, Alexandre Perera-Lluna, Rafael Artuch

Background & aims: Copper is a trace element essential for enzymatic reactions, but excessive accumulation can cause toxicity. Accurate interpretation of serum copper concentrations is crucial for diagnosing conditions such as Wilson's disease, liver dysfunction, and nutritional deficiencies. Current reference intervals often ignore the effect of inflammation and are typically established using discrete age groups rather than modelling age as a continuous variable. This study aimed to establish continuous, age-adjusted reference intervals for serum copper and to develop a method for correcting inflammation-related variability.

Methods: We retrospectively analyzed serum copper concentrations in a pediatric cohort of 4,368 unique samples. Inflammatory status was assessed using erythrocyte sedimentation rate (ESR), fibrinogen, and C-reactive protein (CRP). Samples without inflammation were used to generate age-continuous reference intervals through polynomial regression. To quantify and adjust for inflammation effects, we developed a composite inflammation score using partial least squares regression on standardized values of the three acute-phase markers and applied it to correct copper concentrations in samples exhibiting inflammation.

Results: Serum copper showed a nonlinear relationship with age. Inflammation elevated copper concentrations by approximately 24 %. The composite inflammation score independently predicted this variability in copper concentrations, and adjustment using the score restored copper concentrations within reference limits, reducing the risk of data misinterpretation.

Conclusion: Our findings underscore the necessity of considering both age and inflammation variables when interpreting pediatric serum copper concentrations. We provide continuous, age-adjusted reference intervals and a method to correct for inflammation-related variability, enhancing data interpretation. We propose a proof-of-concept potentially applicable to other biomarkers related with metabolic and nutritional disturbances in chronic and acute diseases.

背景与目的:铜是酶促反应必需的微量元素,但过量积累会引起毒性。准确解释血清铜浓度对于诊断威尔森氏病、肝功能障碍和营养缺乏等疾病至关重要。目前的参考区间往往忽略了炎症的影响,并且通常使用离散年龄组建立,而不是将年龄建模为连续变量。本研究旨在建立连续的、年龄调整的血清铜参考区间,并开发一种纠正炎症相关变异性的方法。方法:我们回顾性分析了4,368个独特样本的儿科队列的血清铜浓度。使用红细胞沉降率(ESR)、纤维蛋白原和c反应蛋白(CRP)评估炎症状态。无炎症的样本通过多项式回归生成年龄连续参考区间。为了量化和调整炎症效应,我们对三种急性期标志物的标准化值使用偏最小二乘回归开发了一种复合炎症评分,并将其应用于校正炎症样品中的铜浓度。结果:血清铜与年龄呈非线性关系。炎症使铜浓度升高约24%。复合炎症评分独立预测了铜浓度的变异性,使用该评分进行调整后,铜浓度恢复在参考范围内,降低了数据误解的风险。结论:我们的研究结果强调了在解释儿童血清铜浓度时考虑年龄和炎症变量的必要性。我们提供了连续的、年龄调整的参考区间和一种方法来纠正炎症相关的变异性,增强了数据的解释。我们提出了一种潜在适用于慢性和急性疾病中与代谢和营养紊乱相关的其他生物标志物的概念验证。
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引用次数: 0
Bariatric surgery improves fibrinolysis in individuals with obesity with and without concomitant type 2 diabetes. 减肥手术可改善伴有或不伴有2型糖尿病的肥胖患者的纤维蛋白溶解。
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-23 DOI: 10.1016/j.clnu.2026.106584
Maja Andersson, Anders Thorell, Peter Henriksson, Anders Kallner, Håkan Wallén, Tomas L Lindahl, Anna Ågren

Background & aims: Hypofibrinolysis is prevalent in obesity and type 2 diabetes mellitus (T2D) and may be involved in their pathophysiology. Metabolic bariatric surgery (MBS) markedly improves both obesity and T2D, but whether these improvements are related to fibrinolysis is not known. In this study, biomarkers of fibrinolysis were assessed before and after MBS in patients with and without T2D.

Methods: A single center prospective cohort study with 2-year follow-up. The participants were adults with obesity with (n = 28) or without T2D (n = 33) undergoing MBS preceded by 2 weeks of a low-calorie diet (LCD). The plasma concentrations of plasminogen activator inhibitor 1 activity (PAI-1act), tissue plasminogen activator activity (tPAact) and antigen (tPAag), plasmin-antiplasmin complexes (PAP) and fibrinogen were determined at baseline, after LCD and at 6 weeks, 1 and 2 years after MBS.

Results: After LCD and prior to MBS, PAI-1act decreased and PAP increased significantly. Two years after MBS, PAI-1act decreased from baseline 29.8 (63) to 3.8 (121) while tPAact increased (0.08 (390) to 0.23 (150) IU), and PAP increased (544 (54) to 814 (60) ng/mL). tPAag and fibrinogen decreased (16.4 (29) to 9.7 (51) ng/mL and 4.15 (23) to 3.82 (20) g/L, respectively); p < 0.001 for all; (geometric means, except tPAact which is arithmetic mean, coefficient of variation (%CV)). There were no differences in fibrinolysis between groups at baseline or after surgery. Multivariate analysis showed that reduction in body weight and fat mass had the most important influence on fibrinolysis.

Conclusion: Fibrinolysis is significantly improved two years after MBS, as also indicated earlier after the two-week LCD. The lack of differences between patients with vs. without T2D suggests that fat mass reduction rather than improvement of glucose control is most important for improved fibrinolysis after MBS. In summary, our results support hypofibrinolysis as a mechanism in the pathophysiology in obesity.

背景与目的:低纤溶在肥胖和2型糖尿病(T2D)中普遍存在,并可能参与其病理生理。代谢减肥手术(MBS)可显著改善肥胖和T2D,但这些改善是否与纤溶有关尚不清楚。在这项研究中,对伴有和不伴有T2D的患者在MBS前后的纤维蛋白溶解生物标志物进行了评估。方法:单中心前瞻性队列研究,随访2年。参与者是肥胖的成年人(n = 28)或没有T2D的成年人(n = 33),他们在进行MBS之前进行了2周的低热量饮食(LCD)。分别在基线、LCD后、MBS后6周、1年和2年测定血浆纤溶酶原激活物抑制剂1 (PAI-1act)、组织纤溶酶原激活物活性(tPAact)和抗原(tPAag)、纤溶酶抗纤溶酶复合物(PAP)和纤维蛋白原浓度。结果:LCD后和MBS前,PAI-1act明显降低,PAP明显升高。MBS后2年,PAI-1act从基线29.8(63)降至3.8 (121),tPAact增加(0.08(390)至0.23 (150)IU), PAP增加(544(54)至814 (60)ng/mL)。tPAag和纤维蛋白原降低(分别为16.4 (29)~ 9.7 (51)ng/mL和4.15 (23)~ 3.82 (20)g/L);P < 0.001;(几何平均值,除算术平均值tPAact外,变异系数(%CV))。在基线和手术后,两组间的纤溶无差异。多因素分析表明,体重和脂肪量的减少对纤维蛋白溶解有最重要的影响。结论:MBS术后2年纤维蛋白溶解明显改善,两周LCD术后亦有明显改善。T2D患者与非T2D患者之间没有差异,这表明减少脂肪质量而不是改善血糖控制对MBS后改善纤维蛋白溶解最重要。总之,我们的研究结果支持低纤溶是肥胖病理生理的一种机制。
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引用次数: 0
A holistic perspective on malnutrition in older adults: Towards an integrated clinical nutrition research guiding framework. 老年人营养不良的整体视角:迈向综合临床营养研究指导框架。
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-22 DOI: 10.1016/j.clnu.2026.106583
Carliene van Dronkelaar, Maarten R Soeters, Philipp Schuetz, Carla M Prado, Nicole Kiss, Michael Tieland, Hinke Kruizenga

Malnutrition is a multifactorial and complex condition with significant consequences for recovery, functional outcomes, and healthcare systems. Research in malnutrition is often limited by single-component interventions, heterogeneous study designs, and variable outcome measures. This perspective paper introduces a practical guiding framework for clinical nutrition research, emphasizing interdisciplinary, multifactorial approaches, co-designed interventions, and pragmatic, adaptive study designs. Evidence from several trials demonstrates that individualized nutritional support delivered by multidisciplinary teams improves clinical outcomes, yet challenges remain in recruitment, adherence, and balancing intervention intensity with patient burden. The framework provides a structured approach to intervention development, outcome selection, and implementation, while remaining flexible to accommodate innovation, context-specific adaptation, and emerging outcome measures. By integrating lessons from prior trials, globally, and promoting systematic reporting and feasibility assessment, this framework aims to enhance the design, comparability, and translational impact of future research in clinical nutrition in older and other clinically vulnerable populations. Adoption of such a framework can guide research prioritization, optimize intervention delivery, and ultimately improve patient recovery and quality of life.

营养不良是一种多因素和复杂的疾病,对恢复、功能结局和卫生保健系统产生重大影响。营养不良的研究经常受到单一成分干预、异质性研究设计和可变结果测量的限制。本文介绍了临床营养研究的实用指导框架,强调跨学科、多因素方法、共同设计的干预措施和实用的适应性研究设计。几项试验的证据表明,多学科团队提供的个性化营养支持改善了临床结果,但在招募、依从性和平衡干预强度与患者负担方面仍然存在挑战。该框架为干预措施的制定、结果的选择和实施提供了一种结构化的方法,同时保持了灵活性,以适应创新、具体情况的适应和新出现的结果措施。通过整合全球范围内先前试验的经验教训,促进系统报告和可行性评估,该框架旨在加强老年人和其他临床弱势群体临床营养未来研究的设计、可比性和转化影响。采用这样的框架可以指导研究的优先次序,优化干预措施的提供,并最终改善患者的康复和生活质量。
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引用次数: 0
Retraction notice to "A randomized trial of iron- and zinc-biofortified pearl millet-based complementary feeding in children aged 12 to 18 months living in urban slums" [Clin Nutr 41 (2022) 937-947]. “城市贫民窟12至18个月儿童铁锌生物强化珍珠米补充喂养的随机试验”[临床医学杂志41(2022)937-947]。
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-21 DOI: 10.1016/j.clnu.2026.106578
Saurabh Mehta, Samantha L Huey, Padmini S Ghugre, Ramesh D Potdar, Sudha Venkatramanan, Jesse T Krisher, Caleb J Ruth, Harsha V Chopra, Aparna Thorat, Varsha Thakker, Lynn Johnson, Laura Powis, Yadurshini Raveendran, Jere D Haas, Julia L Finkelstein, Shobha A Udipi

This article has been retracted: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article is retracted at the request of the authors. During post-publication data re-analyses, the authors found four additional hemoglobin datapoints at the endpoint of the trial reported in the above-named article that move the p-value for the primary outcome - the impact of intervention on the change in hemoglobin concentrations across the duration of the trial - from 0.053 to 0.044. Furthermore, the WHO has recently released a revised set of cutoffs for anemia [WHO 2024], and the anemia cutoff for the age group of interest in this article, 12-23 months, was lowered from a hemoglobin concentration of 11 g/dL to 10.5 g/dL. As such, the authors wish to report these revised estimates of anemia based on the revised WHO cutoffs to keep the findings as updated as possible and useful for guidelines. The Editors considered this request and agreed to the retraction of the article. The authors were invited to submit a revised version of the article, which has been peer-reviewed and accepted for publication in the journal. This retraction notice will be updated with a link to the revised paper when it is published.

本文已被撤回:请参阅Elsevier文章撤回政策(https://www.elsevier.com/about/policies-and-standards/article-withdrawal)。应作者的要求,这篇文章被撤回了。在发表后的数据重新分析中,作者在上述文章中报道的试验终点发现了四个额外的血红蛋白数据点,这些数据点将主要结局(干预对试验期间血红蛋白浓度变化的影响)的p值从0.053移动到0.044。此外,世卫组织最近发布了一套修订后的贫血临界值[WHO 2024],本文关注的年龄组(12-23个月)的贫血临界值从血红蛋白浓度11克/分升降至10.5克/分升。因此,作者希望根据修订后的世卫组织临界值报告这些修订后的贫血估计,以使研究结果尽可能更新并对指南有用。编辑们考虑了这个请求,同意撤回这篇文章。作者被邀请提交一份经过同行评审的修订版文章,并被接受在期刊上发表。本撤稿通知将在论文发表后更新并附上修改后论文的链接。
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引用次数: 0
Safety and immune-regulating effects of Limosilactobacillus reuteri LR08: Preclinical and clinical evidence from a randomized controlled trial. 罗伊氏乳酸杆菌LR08的安全性和免疫调节作用:来自一项随机对照试验的临床前和临床证据
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-20 DOI: 10.1016/j.clnu.2026.106582
Mei Han, Fei Xu, Yao Dong, Jianguo Zhu, Shuguang Fang, Liming Zhao

Background and aims: This study aimed to systematically evaluate the genomic safety of Limosilactobacillus reuteri LR08 and to assess its effects on metabolic health, immune function, and gut microbiota composition in healthy adults..

Methods: Whole-genome sequencing and bioinformatics analyses were conducted to assess the presence of genes related to pathogenicity, antibiotic resistance, and biogenic amine synthesis. In vitro assays and animal studies evaluated hemolytic activity, cytotoxicity, and overall biosafety. A randomized, double-blind, placebo-controlled trial was performed in 48 healthy adults, who received either LR08 (30 billion CFU/day) or placebo for 8 weeks. Clinical, biochemical, and immune parameters were measured, and 16S rRNA sequencing was used to assess gut microbiota changes.

Results: Genomic analysis confirmed the absence of pathogenicity-related, antibiotic resistance, or biogenic amine synthesis genes. In vitro and animal tests demonstrated non-hemolytic, non-cytotoxic characteristics and overall safety. Clinically, LR08 significantly reduced serum uric acid (p < 0.001) and LDL-C levels (p = 0.007) compared with baseline. Compared with placebo, LR08 supplementation significantly increased salivary IgA (p = 0.039), IgM (p = 0.029), and calprotectin levels (p < 0.05). Gut microbiota analysis revealed increased α-diversity, enrichment of beneficial genera including Blautia and Romboutsia, and upregulation of pathways related to carbohydrate metabolism and genetic information processing..

Conclusions: L. reuteri LR08 demonstrates robust genomic safety and favorable effects on metabolic, immune, and gut microbiota profiles in healthy adults. These findings support its potential application as a safe probiotic for metabolic regulation, immune enhancement, and microbiota modulation..

Trial registration number: NCT06875362 (ClinicalTrials.gov).

背景与目的:本研究旨在系统评价罗伊氏乳酸杆菌LR08的基因组安全性,并评估其对健康成人代谢健康、免疫功能和肠道菌群组成的影响。方法:通过全基因组测序和生物信息学分析,评估其致病性、抗生素耐药性和生物胺合成相关基因的存在。体外实验和动物实验评估了溶血活性、细胞毒性和总体生物安全性。一项随机、双盲、安慰剂对照试验在48名健康成人中进行,他们接受LR08(300亿CFU/天)或安慰剂8周。测量临床、生化和免疫参数,并使用16S rRNA测序来评估肠道微生物群的变化。结果:基因组分析证实缺乏致病性相关、抗生素耐药性或生物胺合成基因。体外和动物试验表明,该药物具有非溶血、非细胞毒性和总体安全性。临床上,与基线相比,LR08显著降低血清尿酸(p < 0.001)和LDL-C水平(p = 0.007)。与安慰剂相比,添加LR08显著提高了唾液IgA (p = 0.039)、IgM (p = 0.029)和钙保护蛋白水平(p < 0.05)。肠道菌群分析显示,罗伊氏乳杆菌LR08具有较强的基因组安全性,对健康成人的代谢、免疫和肠道菌群具有良好的影响,α-多样性增加,包括Blautia和Romboutsia在内的有益菌群丰富,碳水化合物代谢和遗传信息处理相关途径上调。这些发现支持其作为一种安全的益生菌用于代谢调节、免疫增强和微生物群调节的潜在应用。
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引用次数: 0
Nutrition care in adults with spinal cord injuries and disorders with pressure injuries: A systematic review of clinical practice guidelines 成人脊髓损伤和压迫性损伤障碍的营养护理:临床实践指南的系统回顾
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-20 DOI: 10.1016/j.clnu.2026.106580
Yiwen Wang , Man Ching Lo , Murray Fisher , Katherine Desneves , Amy Nevin , Priya lyer
Pressure injuries (PIs) are a common and costly complication in adults with spinal cord injuries and disorders (SCI/D), with a global prevalence of 32 % and a lifetime risk exceeding 85 % in Australia. Nutrition is a key factor in the prevention and management of PIs, supporting wound healing, immune function, and overall recovery. This systematic review evaluated the quality, scope, and methodological rigour of 17 international clinical practice guidelines (CPGs) published since 2010 that included nutrition recommendations for PIs in adults with SCI/D. Using the AGREE II and the AGREE-REX tools, this review assessed overall guideline quality and nutrition-specific recommendations mapped to the Nutrition Care Process domains. Seven CPGs were rated high quality with AGREE II, and three with AGREE-REX. While most guidelines focussed on nutrition interventions, limited detail was provided on assessment and monitoring. Considerable variation was found in the rigour and specificity of recommendations. These findings underscore a need for high-quality, SCI/D-specific guidelines that offer consistent, evidence-based, actionable nutrition guidance, particularly in the under-represented areas of assessment and monitoring, to better support PI prevention and treatment in this vulnerable population.
压力损伤(PIs)是脊髓损伤和疾病(SCI/D)成人常见且昂贵的并发症,全球患病率为32%,澳大利亚的终生风险超过85%。营养是预防和管理PIs的关键因素,支持伤口愈合,免疫功能和整体恢复。本系统综述评估了自2010年以来出版的17份国际临床实践指南(cpg)的质量、范围和方法严严性,其中包括SCI/D成人pi的营养建议。使用AGREE II和AGREE- rex工具,本综述评估了总体指南质量和营养护理过程领域的营养特异性建议。7个cpg被AGREE II评为高质量,3个被AGREE- rex评为高质量。虽然大多数指导方针侧重于营养干预措施,但对评估和监测提供的细节有限。在建议的严谨性和特异性方面发现了相当大的差异。这些发现强调,需要制定高质量的SCI/ d特定指南,提供一致的、循证的、可操作的营养指导,特别是在代表性不足的评估和监测领域,以更好地支持这一弱势群体的PI预防和治疗。
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引用次数: 0
Prospective study of anamorelin in pancreatic cancer cachexia: Clinical and translational insights into response heterogeneity anamorelin治疗胰腺癌恶病质的前瞻性研究:对反应异质性的临床和翻译见解
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-20 DOI: 10.1016/j.clnu.2026.106581
Ryosuke Matsukane , Haruna Minami , Nao Fujimori , Keijiro Ueda , Yasuhiro Komori , Yu Takamatsu , Takahiro Ueda , Minako Kimura , Chitose Matsuzaki , Takanori Tanaka , Aimi Morito , Saki Kuwahara , Masako Hashimoto , Satoshi Hirai , Tomiko Yokoyama , Shigeru Ishida , Takeshi Hirota , Yoshihiro Ogawa , Mayako Uchida

Background & aims

Clinical evidence for anamorelin in pancreatic cancer is extremely limited, despite its approval in Japan. This study provides the first prospective evaluation of anamorelin specifically in pancreatic cancer, aiming to assess real-world efficacy and safety and to identify factors contributing to treatment-response heterogeneity through integrated biomarker analyses.

Methods

This prospective, single-center, observational study enrolled 24 patients with unresectable or metastatic pancreatic cancer who developed cachexia. Efficacy was evaluated in patients who received anamorelin for >1 month. The primary endpoint was change in LBM from baseline, and secondary endpoints included the LBM-based response rate. Responders were defined as those who maintained or increased LBM during treatment. Safety assessment focused on treatment-related adverse events, particularly hyperglycemia.

Results

Seventeen patients were included in the efficacy analysis (median age, 68 years; median weight loss, 8.3 %). The mean LBM increased by 0.9 and 1.4 kg at 1 and 2 months, respectively. Quality-of-life scores related to appetite, weight gain, and total scores improved significantly at 1 month. Ten patients (58.8 %) were classified as responders, showing significant LBM gains from baseline (+2.4 kg at 1 month, +3.4 kg at 2 months, p < 0.001). Handgrip strength also improved in responders compared with non-responders at 2 months (+1.7 kg vs −2.0 kg, p < 0.01). Serum levels of insulin-like growth factor-1, inflammatory cytokines, ghrelin, and leptin levels did not differ significantly between baseline and 1 month. However, lower baseline body mass index (BMI) was strongly associated with response (sensitivity 85.7 %, specificity 90.0 %, area under the curve [AUC] 0.886, cutoff 20.4 kg/m2; p = 0.008). In the safety analysis (n = 23), 34.8 % experienced hyperglycemia of any grade, and 26.1 % developed grade ≥2 hyperglycemia—higher than in NSCLC trials. Median time to onset was 4.5 days (range, 2–18). Baseline diabetes was significantly associated with grade ≥2 hyperglycemia. This event was highly predictable by low pre-treatment ΔC-peptide levels (6–0 min; sensitivity 100.0 %, specificity 91.7 %, cut-off 1.03 ng/mL, AUC 0.967; p = 0.0032).

Conclusions

Anamorelin effectively improved LBM and appetite/QOL domains in pancreatic cancer, particularly in patients with low BMI. However, hyperglycemia—especially in those with impaired insulin secretion—requires careful monitoring. Baseline BMI and insulin secretion capacity should be evaluated before initiating therapy, and these findings provide preliminary insight into treatment response heterogeneity in pancreatic cancer cachexia.
背景和目的尽管anamorelin在日本获得批准,但其治疗胰腺癌的临床证据极其有限。本研究首次对anamorelin在胰腺癌中的特异性治疗进行了前瞻性评估,旨在通过综合生物标志物分析评估真实世界的疗效和安全性,并确定导致治疗-反应异质性的因素。方法:本前瞻性、单中心、观察性研究纳入24例不可切除或转移性恶性肿瘤患者。对接受阿纳莫瑞林治疗1个月的患者进行疗效评估。主要终点是LBM较基线的变化,次要终点包括基于LBM的缓解率。应答者被定义为在治疗期间维持或增加LBM的人。安全性评估侧重于治疗相关的不良事件,特别是高血糖。结果17例患者纳入疗效分析(中位年龄68岁,中位体重减轻8.3%)。在1个月和2个月时,平均体重分别增加0.9和1.4公斤。与食欲、体重增加和总分相关的生活质量评分在1个月时显著改善。10名患者(58.8%)被归类为应答者,显示出较基线显著的体重增加(1个月+2.4 kg, 2个月+3.4 kg, p < 0.001)。在2个月时,有反应者的握力也比无反应者有所改善(+1.7 kg vs - 2.0 kg, p < 0.01)。血清胰岛素样生长因子-1、炎症细胞因子、胃饥饿素和瘦素水平在基线和1个月之间没有显著差异。然而,较低的基线体重指数(BMI)与疗效密切相关(敏感性85.7%,特异性90.0%,曲线下面积[AUC] 0.886,截止值20.4 kg/m2; p = 0.008)。在安全性分析中(n = 23), 34.8%的患者出现了任何级别的高血糖,26.1%的患者出现了≥2级的高血糖,高于NSCLC试验。中位发病时间为4.5天(范围2-18天)。基线糖尿病与≥2级高血糖显著相关。低预处理ΔC-peptide水平(6-0 min;敏感性100.0%,特异性91.7%,截止值1.03 ng/mL, AUC 0.967; p = 0.0032)可高度预测该事件。结论sanamorelin能有效改善胰腺癌患者的LBM和食欲/生活质量域,特别是对低BMI患者。然而,高血糖——尤其是那些胰岛素分泌受损的人——需要仔细监测。在开始治疗前应该评估基线BMI和胰岛素分泌能力,这些发现为胰腺癌恶病质的治疗反应异质性提供了初步的见解。
{"title":"Prospective study of anamorelin in pancreatic cancer cachexia: Clinical and translational insights into response heterogeneity","authors":"Ryosuke Matsukane ,&nbsp;Haruna Minami ,&nbsp;Nao Fujimori ,&nbsp;Keijiro Ueda ,&nbsp;Yasuhiro Komori ,&nbsp;Yu Takamatsu ,&nbsp;Takahiro Ueda ,&nbsp;Minako Kimura ,&nbsp;Chitose Matsuzaki ,&nbsp;Takanori Tanaka ,&nbsp;Aimi Morito ,&nbsp;Saki Kuwahara ,&nbsp;Masako Hashimoto ,&nbsp;Satoshi Hirai ,&nbsp;Tomiko Yokoyama ,&nbsp;Shigeru Ishida ,&nbsp;Takeshi Hirota ,&nbsp;Yoshihiro Ogawa ,&nbsp;Mayako Uchida","doi":"10.1016/j.clnu.2026.106581","DOIUrl":"10.1016/j.clnu.2026.106581","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Clinical evidence for anamorelin in pancreatic cancer is extremely limited, despite its approval in Japan. This study provides the first prospective evaluation of anamorelin specifically in pancreatic cancer, aiming to assess real-world efficacy and safety and to identify factors contributing to treatment-response heterogeneity through integrated biomarker analyses.</div></div><div><h3>Methods</h3><div>This prospective, single-center, observational study enrolled 24 patients with unresectable or metastatic pancreatic cancer who developed cachexia. Efficacy was evaluated in patients who received anamorelin for &gt;1 month. The primary endpoint was change in LBM from baseline, and secondary endpoints included the LBM-based response rate. Responders were defined as those who maintained or increased LBM during treatment. Safety assessment focused on treatment-related adverse events, particularly hyperglycemia.</div></div><div><h3>Results</h3><div>Seventeen patients were included in the efficacy analysis (median age, 68 years; median weight loss, 8.3 %). The mean LBM increased by 0.9 and 1.4 kg at 1 and 2 months, respectively. Quality-of-life scores related to appetite, weight gain, and total scores improved significantly at 1 month. Ten patients (58.8 %) were classified as responders, showing significant LBM gains from baseline (+2.4 kg at 1 month, +3.4 kg at 2 months, p &lt; 0.001). Handgrip strength also improved in responders compared with non-responders at 2 months (+1.7 kg vs −2.0 kg, p &lt; 0.01). Serum levels of insulin-like growth factor-1, inflammatory cytokines, ghrelin, and leptin levels did not differ significantly between baseline and 1 month. However, lower baseline body mass index (BMI) was strongly associated with response (sensitivity 85.7 %, specificity 90.0 %, area under the curve [AUC] 0.886, cutoff 20.4 kg/m<sup>2</sup>; p = 0.008). In the safety analysis (n = 23), 34.8 % experienced hyperglycemia of any grade, and 26.1 % developed grade ≥2 hyperglycemia—higher than in NSCLC trials. Median time to onset was 4.5 days (range, 2–18). Baseline diabetes was significantly associated with grade ≥2 hyperglycemia. This event was highly predictable by low pre-treatment ΔC-peptide levels (6–0 min; sensitivity 100.0 %, specificity 91.7 %, cut-off 1.03 ng/mL, AUC 0.967; p = 0.0032).</div></div><div><h3>Conclusions</h3><div>Anamorelin effectively improved LBM and appetite/QOL domains in pancreatic cancer, particularly in patients with low BMI. However, hyperglycemia—especially in those with impaired insulin secretion—requires careful monitoring. Baseline BMI and insulin secretion capacity should be evaluated before initiating therapy, and these findings provide preliminary insight into treatment response heterogeneity in pancreatic cancer cachexia.</div></div>","PeriodicalId":10517,"journal":{"name":"Clinical nutrition","volume":"58 ","pages":"Article 106581"},"PeriodicalIF":7.4,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dietary flavonoid intake and psychological well-being – A bidirectional relationship 膳食类黄酮摄入量与心理健康-双向关系
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-19 DOI: 10.1016/j.clnu.2026.106579
Alysha S. Thompson , Nicola P. Bondonno , Yan Lydia Liu , Farah Qureshi , Laura D. Kubzansky , Claudia Trudel-Fitzgerald , Julia K. Boehm , Eric B. Rimm , Aedín Cassidy

Background and aim

Higher dietary flavonoid intake has been associated with lower risks of mortality and major chronic disease, yet its relationship with psychological well-being (PWB), a key contributor to health and quality of life, remains unclear. This study aimed to investigate bidirectional associations between dietary flavonoid intake and two PWB facets: happiness (positive emotional state) and optimism (generalized expectation of positive outcomes). Specifically, we examined whether (1) overall flavonoid-rich dietary patterns (flavodiet score), (2) intake of specific flavonoid-rich foods, and (3) total flavonoid and subclass intakes were each associated with happiness and optimism over time.

Methods

Data were drawn from the Nurses’ Health Study to form two analytical samples. Flavonoid intake measured in 1990 (n = 44,659) was examined in relation to sustained happiness (1992–2000) while intake in 2002 (n = 36,723) was analysed in relation to sustained optimism (2004–2012). Secondary analyses assessed whether higher baseline levels of each PWB facet were associated with sustained higher flavonoid intake, over up to 18 years. Associations were assessed using generalized estimating equations, adjusting for potential confounders.

Results

Higher flavodiet scores were associated with a 3–6 % higher likelihood of sustained happiness [RRQ4vsQ1 (95 % CI): 1.03 (1.02–1.05)] and optimism [RRQ4vsQ1 (95 % CI): 1.06 (1.01–1.11)]. Specific flavonoid-rich foods (strawberries, apples, oranges, grapefruit, blueberries) were associated with a 3–16 % greater likelihood of sustained PWB, across the two facets. Similarly, total flavonoid and subclass intakes were associated with a 2–18 % greater likelihood of sustained PWB. Women with higher baseline levels of happiness or optimism were also more likely to sustain a higher flavonoid intake.

Conclusions

Consuming ∼3 servings/day of flavonoid-rich foods is associated with sustained PWB, and higher baseline PWB is associated with sustained higher flavonoid intake over up to 18 years. This bidirectional relationship suggests that integrated interventions targeting both diet and well-being may help promote long-term health and reduce chronic disease risk.
背景和目的较高的膳食类黄酮摄入量与较低的死亡率和主要慢性疾病风险相关,但其与心理健康(PWB)的关系尚不清楚,PWB是健康和生活质量的关键因素。本研究旨在探讨膳食类黄酮摄入量与幸福(积极情绪状态)和乐观(积极结果的普遍期望)两个PWB方面的双向关系。具体来说,我们研究了(1)总体富含类黄酮的饮食模式(flavodiet评分),(2)摄入特定富含类黄酮的食物,以及(3)摄入总类黄酮和亚类黄酮是否与长期的快乐和乐观有关。方法从护士健康调查中抽取数据,形成两个分析样本。1990年的类黄酮摄入量(n = 44,659)与持续幸福(1992-2000)的关系进行了研究,2002年的摄入量(n = 36,723)与持续乐观(2004-2012)的关系进行了分析。二次分析评估了在长达18年的时间里,较高的PWB各方面基线水平是否与持续较高的类黄酮摄入量有关。使用广义估计方程评估关联,调整潜在混杂因素。结果高脂肪饮食评分与高3 - 6%的持续快乐的可能性相关[RRQ4vsQ1 (95% CI): 1.03(1.02-1.05)]和乐观[RRQ4vsQ1 (95% CI): 1.06(1.01-1.11)]。特定的富含类黄酮的食物(草莓、苹果、橙子、葡萄柚、蓝莓)在这两个方面与持续PWB的可能性增加3 - 16%有关。同样,总黄酮和亚类摄入量与持续PWB的可能性增加2 - 18%相关。幸福或乐观基线水平较高的女性也更有可能维持较高的类黄酮摄入量。结论:每天食用~ 3份富含类黄酮的食物与持续的PWB有关,较高的基线PWB与长达18年的持续较高的类黄酮摄入量有关。这种双向关系表明,以饮食和健康为目标的综合干预措施可能有助于促进长期健康并降低慢性病风险。
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引用次数: 0
Proteins in artificial nutrition: toward an individualized and phase-specific prescription 人工营养中的蛋白质:走向个体化和阶段性处方
IF 7.4 2区 医学 Q1 NUTRITION & DIETETICS Pub Date : 2026-01-14 DOI: 10.1016/j.clnu.2026.106577
Philipp Schuetz , Frank Carrera-Gil , Carla Wunderle
Protein is a central component of artificial nutrition, yet its optimal dose and timing remain controversial. Provision of both insufficient and excessive protein is associated with adverse outcomes. Inadequate intake promotes negative nitrogen balance, muscle wasting, impaired tissue healing and repair, and increased risk of infection, whereas excessive protein may exceed metabolic capacity, causing azotemia, hepatic or renal strain, and reduced metabolic flexibility — particularly in patients with renal dysfunction. Emerging evidence indicates that the optimal protein dose is strongly influenced by patient-specific characteristics and evolves throughout the course of illness, supporting an individualized, phase-adapted strategy for protein provision rather than a fixed universal target. During early critical illness, catabolism predominates and high protein doses may not be effectively utilized. In contrast, during recovery and stabilization, higher protein targets appear beneficial for restoring lean body mass and functional capacity. This dynamic trajectory underscores the need to abandon universal recommendations in favor of personalized prescriptions. Although instruments such as nitrogen balance, body composition analysis, and indirect calorimetry can provide information about protein dosage, their routine use in clinical practice is limited and interpretation in acute illnesses remains difficult. Pragmatic, bedside strategies and the phenotyping of patients using biomarkers are, therefore, needed to tailor protein provision according to disease stage, organ function, and anabolic capacity. This opinion paper explores mechanistic insights, evidence from clinical trials, and guidelines on protein supplementation, explores biomarker-driven personalization, and highlights ongoing challenges and future research priorities in nutritional therapy.
蛋白质是人工营养的核心成分,但其最佳剂量和时间仍然存在争议。蛋白质供应不足和过量都与不良后果有关。摄入不足会促进负氮平衡,肌肉萎缩,组织愈合和修复受损,并增加感染风险,而过量的蛋白质可能超过代谢能力,导致氮血症,肝脏或肾脏应变,并降低代谢灵活性-特别是在肾功能不全的患者中。新出现的证据表明,最佳蛋白质剂量受到患者特异性特征的强烈影响,并在整个疾病过程中不断发展,这支持个性化的、适应阶段的蛋白质供应策略,而不是固定的普遍目标。在早期危重疾病期间,分解代谢占主导地位,高蛋白剂量可能无法有效利用。相反,在恢复和稳定期间,较高的蛋白质目标似乎有利于恢复瘦体重和功能能力。这一动态轨迹强调了放弃普遍建议而采用个性化处方的必要性。虽然氮平衡、身体成分分析和间接量热等仪器可以提供蛋白质剂量的信息,但它们在临床实践中的常规应用有限,在急性疾病中的解释仍然困难。因此,需要实用的床边策略和使用生物标志物的患者表型,根据疾病分期、器官功能和合成代谢能力定制蛋白质供应。本文探讨了蛋白质补充的机理见解、临床试验证据和指南,探讨了生物标志物驱动的个性化,并强调了营养治疗中正在面临的挑战和未来的研究重点。
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引用次数: 0
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Clinical nutrition
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