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Summary Rationale This initiative is focused on building a global consensus around core diagnostic criteria for malnutrition in adults in clinical settings. Methods In January 2016, the Global Leadership Initiative on Malnutrition (GLIM) was convened by several of the major global clinical nutrition societies. GLIM appointed a core leadership committee and a supporting working group with representatives bringing additional global diversity and expertise. Empirical consensus was reached through a series of face‐to‐face meetings, telephone conferences, and e‐mail communications. Results A two‐step approach for the malnutrition diagnosis was selected, i.e., first screening to identify “at risk” status by the use of any validated screening tool, and second, assessment for diagnosis and grading the severity of malnutrition. The malnutrition criteria for consideration were retrieved from existing approaches for screening and assessment. Potential criteria were subjected to a ballot among the GLIM core and supporting working group members. The top five ranked criteria included three phenotypic criteria (weight loss, low body mass index, and reduced muscle mass) and two etiologic criteria (reduced food intake or assimilation, and inflammation or disease burden). To diagnose malnutrition at least one phenotypic criterion and one etiologic criterion should be present. Phenotypic metrics for grading severity as Stage 1 (moderate) and Stage 2 (severe) malnutrition are proposed. It is recommended that the etiologic criteria be used to guide intervention and anticipated outcomes. The recommended approach supports classification of malnutrition into four etiology‐related diagnosis categories. Conclusion A consensus scheme for diagnosing malnutrition in adults in clinical settings on a global scale is proposed. Next steps are to secure further collaboration and endorsements from leading nutrition professional societies, to identify overlaps with syndromes like cachexia and sarcopenia, and to promote dissemination, validation studies, and feedback. The diagnostic construct should be re‐considered every 3–5 years.

There is a pressing need to expand the production and consumption of alternative protein sources from plants, fungi, insects, and algae from both nutritional and sustainability perspectives. It is well known that the postprandial rise in plasma amino acid concentrations and subsequent muscle anabolic response is greater after the ingestion of animal-derived protein sources, such as dairy, meat, and eggs, than plant-based proteins. However, emerging evidence shows that a similar muscle anabolic response is observed-despite a lower and slower postprandial aminoacidemia-after the ingestion of alternative protein sources compared with animal-derived protein sources. Therefore, a comprehensive analysis of plasma amino acid kinetics after the ingestion of alternative protein sources would play a significant role in recognizing and identifying the anabolic properties of these protein sources, allowing for the implementation of the best nutritional intervention strategies, contributing to more sustainable food production, and developing new medical nutritional products with optimal impacts on muscle mass, strength, and function, both in terms of health and disease. Therefore, this narrative review is focused on postprandial amino acid kinetics (the area under the curve, peak, and time to reach the peak concentration of amino acids) based on experimental randomized controlled trials performed in young and older adults following the ingestion of different novel, sustainable, and alternative protein sources.

To investigate the potential contribution of chest wall muscle area (CWMA) to the ventilatory efficiency and exercise capacity in patients with Systemic Sclerosis (SSc) without interstitial lung disease (ILD). Forty-four consecutive SSc patients [F = 37, median age 53.5 years (IQR 43.5-58)] were examined using chest high-resolution computed tomography (HRCT), pulmonary function tests and cardiopulmonary exercise testing (CPET). The CWMA was evaluated at the level of the ninth thoracic vertebra on CT images by two independent evaluators blinded to the patient information. CPET parameters analyzed were maximum oxygen uptake (VO2 max) and VO2 at anaerobic threshold (VO 2 @AT); minute ventilation (VE); maximum tidal volume (VT). A statistically significant positive correlation was found between CWMA and maximum workload (r = 0.470, p < 0.01), VO2 max ml/min (r = 0.380, p < 0.01), VO2@AT (r = 0.343, p < 0.05), VE (r = 0.308, p < 0.05), VT (r = 0.410, p < 0.01) and VO2/heart rate (r = 0.399, p < 0.01). In multiple regression analysis, VO2 max (ml/min) was significantly associated with CWMA [β coefficient = 5.226 (95% CI 2.824, 7.628); p < 0.001], diffusing capacity for carbon monoxide (DLco) [β coefficient = 6.749 (95% CI 1.460, 12.039); p < 0.05] and body mass index (BMI) [β coefficient = 41.481 (95% CI 8.802, 74.161); p < 0.05]. In multiple regression analysis, maximum workload was significantly associated with CWMA [β coefficient = 0.490 (95% CI 0.289, 0.691); p < 0.001], DLco [β coefficient = 0.645 (95% CI 0.202, 1.088); p < 0.01] and BMI [β coefficient = 3.747 (95% CI 1.013, 6.842); p < 0.01]. In SSc-patients without ILD, CWMA represents an important variable in exercise capacity and can be evaluated by the mediastinal window available in the HRCT images required for lung disease staging., Competing Interests: Declarations. Conflict of interest: The authors declare that this research was conducted without commercial or financial relationships that could represent a potential conflict of interest. Ethical approval and Informed consent: This study was approved by the Ethics Committee of Sapienza University (IRB 0304) and written informed consent was obtained from all patients. Human and animal rights statement: The present study was conducted according to the Declaration of Helsinki (1964) and its later amendments., (© 2024. The Author(s).)

Introduction: Increased serum uric acid (SUA) levels are found in cardiovascular and kidney diseases, associated with the development of vascular injury. Uric acid stimulates the inflammatory pathways, promotes vascular smooth muscle cells proliferation, activates renin-angiotensin system leading to the development and progression of vascular damage. Renal function-normalized uric acid [SUA to serum creatinine ratio (SUA/SCr)] has been suggested to be a better indicator of uric acid., Aim: To investigate the correlation between SUA level and SUA/SCr in the development of chronic and vascular lesions (CVL) in patients with primary glomerulonephritis (GN)., Methods: A retrospective observational study was conducted in 95 consecutive renal native biopsies performed at Policlinico Umberto I of Rome (Italy). Patient inclusion criteria were age ≥ 18 years, a renal biopsy confirming diagnosis of primary GN, the availability of complete demographic, clinical, pathological, and laboratory data., Results: Median SCr was 1.06 mg/dl (IQR 0.77;1.70) with a median eGFR of 70.40 ml/min (IQR 40.40;105). Median SUA was 5.90 mg/dl (IQR 4.30;6.90) and median SUA/SCr was 4.70 (IQR 3.20;6.80). CVL were reported in 56 (58.9%) patients. Median SUA/SCr was significantly lower in patients with CVL than patients without CVL [3.95 (IQR 2.65;6) vs 5.90 (IQR 4.30;7.20), p<0.01]. Logistic regression analysis showed that SUA/SCr ≤ 4.05 [OR 5.451 (95% CI 1.222;24.325), p<0.05] was independently associated with CVL., Conclusions: CVL play a crucial role in the progression of kidney disease. SUA/SCr ≤ 4.05 is associated with CVL in patients with primitive GN., Competing Interests: Declarations. Conflict of interest: No conflict of interest to declare., (© 2024. The Author(s).)

Background: A diet rich in fiber, especially soluble fiber, causes cholestatic liver damage and fibrosis in animal models with intestinal dysbiosis, high serum bile acid concentrations, and congenital portosystemic shunts (PSs), but no data on patients with cirrhosis (CIRs) are available., Objectives: To investigate whether dietary fiber consumption was associated with clinical outcomes of CIRs and whether their effect differed according to the presence of PSs., Methods: Daily soluble and insoluble fiber intake was extrapolated from 3-d food diaries in 25 patients with chronic hepatitis (CH) and 80 CIRs outpatient liver transplant candidates abstinent from alcohol and nonviremic for ≥6 mo. In CIRs, the presence of PSs was verified by computed tomography, and the model for end-stage liver disease (MELD) score was calculated at enrollment and after 6 mo., Results: PSs were present in 48 (60%) CIRs. The MELD score after 6 mo, compared with enrollment, had improved in 19 and 10 CIRs with and without PSs, respectively. By adjusting for confounders in logistic regression models we found that improvement in MELD over time was inversely associated with insoluble fiber consumption expressed in milligrams per kilogram (mg/kg) body weight in CIRs without PSs [odds ratio (OR): 0.968; 95% confidence interval (CI): 0.939, 0.997; P = 0.005] but with soluble fiber consumption in CIRs with PSs [OR: 0.946; 95% CI: 0.912, 0.982; P = 0.001]. In CIRs with PSs, soluble fiber consumption was inversely associated with normal serum alkaline phosphatase values at enrollment [OR: 0.964; 95% CI: 0.963, 0.993; P = 0.010]. CHs with normal serum alanine transaminase consumed significantly more soluble fiber (p=0.015) than those with abnormal alanine transaminase., Conclusions: The clinical impact of dietary fiber changes from beneficial to harmful as the stage of chronic liver disease progresses. In particular, in the advanced cirrhosis stage with PSs, soluble fiber intake appears to significantly influence disease progression and should be kept low., Competing Interests: The authors report no conflicts of interest., (© 2024 The Authors.)

Background: Resolvins, which are divided into series D (RvD) and E (RvE), originate from omega-3 fatty acids, DHA and EPA and were recently found to be involved in the modulation of inflammation in some tumors, including breast cancer (BC). We aimed to assess the resolvin profiles (RvD1, RvD2, RvD3 and RvE1) in the plasma of BC patients compared with those of controls and to determine differences in their concentrations according to BC presentation and immunohistochemical characteristics., Methods: We considered BC patients (sporadic, familiar and BRCA1/2-mutated forms) naïve to any anticancer treatment and controls affected by nonmalignant breast disease. According to the BC immunohistochemical characteristics, we identified the luminal-A, luminal-B, HER2 + and triple-negative subtypes. The levels of RvD1, RvD2, RvD3 and RvE1 in the plasma of all the participants were measured via ELISA kits., Results: We enrolled 64 women, 53 with BC (age 51 ± 10 y) and 11 controls (age 49 ± 7 y). Twenty-seven patients presented with sporadic BC, 16 with a positive history of BC (familiar), and 10 with BRCA 1/2 gene mutations. Compared with control patients, BC patients presented higher levels of RvD1 (p = 0.015), and no differences were detected for RvD2, 3 or RvE1. In BC, all resolvin levels were positively correlated with each other (p < 0.001). The expression of RvD1 and RvD3 was lower in the mutated group than in the familiar and sporadic groups (p < 0.05). The expression of RvD2 and RvE1 tended to be lower in the BRCA 1/2-mutated group than in the sporadic and familiar BC patients (p = 0.051 and p = 0.062, respectively). No differences in plasma resolvin levels were observed according to immunohistochemical characteristics (luminal A, luminal B, HER2+, triple-negative). However, RvD1 was lower in triple-negative patients than in patients with the other BC subtypes (p = 0.023). In terms of Ki-67 expression, RvD3 expression was lower in patients with high Ki-67 expression ([Formula: see text]20%) than in those with low Ki-67 expression (<20%) (p = 0.034)., Conclusion: This is the first human study profiling specific plasma resolvin levels in BC patients, which revealed low plasma levels of some resolvins in patients with BRCA1/2 mutations, triple-negative subtypes and high Ki-67 expression, potentially impacting treatment response and prognosis., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki and approved by the local Ethics Committee (Sapienza University, Policlinico Umberto I, Rome, Italy— prot. n. 588/13). Written informed consent was obtained from all patients and controls enrolled in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background/objectives: The pathophysiology of cancer anorexia is multifactorial and unclear. Transcriptomic analysis from PBMCs RNA showed diverse patterns of gene expression pathways in anorexic cancer patients. We assessed whether the different transcriptomic signatures are modulated by DNA methylation in lung cancer patients presenting with poor appetite., Methods: Lung cancer patients and controls were enrolled, and anorexia was assessed by the FAACT-score questionnaire. Genome-wide DNA methylation was determined by Human Infinium MethylationEPIC BeadChip Kit. Data from genome-wide methylation analysis were merged with those from gene expression analysis, previously obtained by RNA sequencing (NGS). Four groups of genes were identified for each comparison: hypermethylated repressed, hypermethylated induced, hypomethylated repressed, and hypomethylated induced., Results: Cancer patients ( n = 16) showed 382 differentially methylated genes when compared with controls ( n = 8). Anorexic patients ( n = 8) presented 586 hypomethylated and 174 hypermethylated genes compared with controls. In anorexic patients vs. non-anorexic ( n = 8), 211 genes were identified as hypomethylated and 90 hypermethylated. When microarray methylation data were merged with transcriptomic data by RNA sequencing, we observed significant differences in anorexic patients vs. controls; a total of 42 genes resulted as hypomethylated and induced, 5 hypermethylated repressed, 10 hypermethylated induced, and 15 hypomethylated repressed. The CG sites analyzed by targeted bisulfite NGS in four genes of interest (FLNA, PGRMC1, GNL3L, and FHL1) resulting as hypomethylated in anorexic vs. controls allowed the validation of the data obtained from DNA methylation. Interestingly, the four genes resulted as hypomethylated in anorexic patients vs. non-anorexic patients and vs. controls ( p < 0.0001)., Conclusions: Our data support that methylation is implicated in cancer-associated anorexia and nutritional derangements among lung cancer patients.

The current global trend in the nutrition, epidemiologic and demographic transitions collectively alarms the need to pursue a sustainable protein diet that respects ecosystem and biodiversity from alternative sources, such as algae, fungi and edible insects. Then, changing the nutrition reality is extremely important to impede the global syndemic of obesity, undernutrition and climate change. This review aims to synthesize the published literature on the potential roles of alternative proteins and their derived bioactive peptides in preventive and clinical nutrition, identify research gaps and inform future research areas. Google Scholar and PubMed databases from their inception up to 30 June 2024 were searched using keywords to access pertinent articles published in English language for the review. Overall, proteins derived from algae, fungi, and edible insects are high-quality proteins as animal sources and demonstrate significant potential as a sustainable source of bioactive peptides, which are metabolically potent and have negligible adverse effects. They show promise to prevent and treat diseases associated with oxidative stress, obesity, diabetes, cancer, cardiovascular disease (especially hypertension), and neurodegenerative diseases. Given the abundance of algae, fungi and insect peptides performed in vitro or in vivo animals, further clinical studies are needed to fully establish their safety, efficacy and practical application in preventive and clinical nutrition. Additionally, social and behavioral change communication strategies would be important to increase health awareness of nutritional benefits and promote consumer acceptance of alternative protein sources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Yimam, Andreini, Carnevale and Muscaritoli.)

To quantify the circulating levels of novel serum biomarkers including GDF-15, PIVKA-II, sdLDL, suPAR, and of CRP in hospitalized COVID-19 patients compared with healthy subjects, and to evaluate their association(s) with outcomes in COVID-19. We considered patients with confirmed COVID-19, hospitalized in an Internal Medicine ward. The clinical characteristics were collected, including the number and type of comorbidities. Serum levels of GDF-15, PIVKA-II, suPAR, sdLDL, as well as CRP were measured. As outcomes, we considered Intensive Care Unit (ICU) transfer or death, as well as the length of stay (days) and in-hospital complications. Data were statistically analyzed, as appropriate, and a p value < 0.05 was considered significant. Ninety-three patients and 20 healthy controls were enrolled. COVID-19 patients vs. controls showed higher median levels of GDF-15 (p < 0.0001), PIVKA-II (p < 0.0001) and sdLDL (p = 0.0002), whereas no difference was observed for suPAR. In COVID-19 patients, the most frequent comorbidities were arterial hypertension (62.4%) and cardiovascular disease (30.1%). GDF-15 levels positively correlated with age (r = 0.433, p < 0.0001), and this correlation was confirmed for suPAR (r = 0.308, p = 0.003) and CRP (Rho = 0.40 p < 0.0001), but not for PIVKA-II and sdLDL. Higher GDF-15 levels were associated with a higher number of comorbidities (p = 0.021). The median length of stay was 22 (15; 30) days. During hospitalization, 15 patients (16%) were ICU transferred, and 6 (6.45%) died. GDF-15 serum levels correlated with the length of stay (rho = 0.27 p = 0.010), and were associated with ICU transfer or death (p = 0.003), as well as PIVKA-II (p = 0.038) and CRP (p < 0.001). Moreover, higher GDF-15 and PIVKA-II serum levels were associated with infectious complications (p = 0.008 and p = 0.017, respectively). In this cohort of hospitalized COVID-19 patients, novel inflammatory biomarkers, including GDF-15, suPAR and PIVKA II were associated with some patient's clinical characteristics, complications, and poor outcomes., (© 2024. The Author(s).)

Background: Adipose tissue (AT) wasting in cancer is an early catabolic event with negative impact on outcomes. Circulating miRNAs may promote body weight loss and cachexia. We measured circulating miRNAs linked to AT alterations and compared their levels between i) gastrointestinal (GI) cancer patients and controls, ii) cachectic and non-cachectic cancer patients, and iii) according to adiposity level and its distribution., Methods: Patients with GI cancer and subjects with benign diseases as controls were considered. Cachexia was assessed and adiposity evaluated by CT-scan for subcutaneous AT area (SAT), visceral AT area and the total AT area (TAT). MiRNAs involved were measured in plasma by RT-qPCR., Results: 37 naïve GI cancer patients and 14 controls were enrolled. Patients with cachexia presented with lower SAT compared to non-cachectic ( p < 0.05). In cancer patients, we found higher levels of miR-26a, miR-128, miR-155 and miR-181a vs. controls ( p < 0.05). Cancer patients with BMI < 25 kg/m 2 showed higher levels of miR-26a vs. those with BMI ≥ 25 ( p = 0.035). MiR-26a and miR-181a were higher in cachectic and non-cachectic vs. controls ( p < 0.05). Differences between cachectic and controls were confirmed for miR-155 ( p < 0.001) but not between non-cachectic vs. control ( p = 0.072). MiR-155 was higher in cachectic patients with low TAT vs. those without cachexia and high TAT ( p = 0.036)., Conclusion: Our data confirm a modulation of specific and different miRNAs involved in AT metabolism in cancer and cachexia. MiR-155 levels were higher in patients presenting with cachexia and low adiposity with implications in the pathogenic mechanisms and clinical consequences of GI cancer patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tambaro, Imbimbo, Pace, Amabile, Rizzo, Orlando, Lauteri, Ramaccini, Catalano, Nigri, Muscaritoli and Molfino.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5-10% of all patients with end-stage kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss., Methods: We evaluated kidney function by estimated glomerular filtration rate (eGFR) in 32 ADPKD patients in different stages of kidney disease at T0 and after a 24-month follow up (T1). Patients were divided into two groups: Rapid disease progression ([RP], n 15) and Non-rapid disease progression ([NRP], n 17), according to the Mayo Clinic classification criteria. At T0, ADPKD patients underwent plasma sampling for quantitative analysis of h-miR-17-5p, h-miR-21-5p and h-miR-199a-5p microRNA expression, using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) method and a 3 T magnetic resonance imaging (MRI), using an advanced MRI imaging protocol, for the quantification of total kidney volume (TKV), total perfusion volume (TPV) and total fibrotic volume (TFV)., Results: The expression of h-miR17-5p was higher (p < 0.05) in ADPKD patients with rapid disease progression. h-miR-17-5p, h-miR-21-5p and h-mir-199-5p showed a positive and significant correlation with the eGFR slope (mL/min/1.73 m 2 /year) (p < 0.05) but not with the eGFR at both T0 and T1. Both total fibrotic volume (cm 3 ) and height-adjusted total fibrotic volume (cm 3 /m) were positively and significantly correlated to h-miR 21-5p and h-miR 199-5p (p < 0.05), but not to total kidney volume (cm 3 ) and height-adjusted total kidney volume (cm 3 /m)., Conclusions: The microRNAs we studied were associated with fibrosis and renal damage, suggesting their possible role as biomarkers able to identify ADPKD patients at high risk of disease progression regardless of the degree of kidney function, and therefore suitable for medical therapy, and may help uncovering new molecular mechanisms underlying cystogenesis., (© 2024. The Author(s).)

Background & Aims: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation in support of the etiologic criterion for inflammation., Methods: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified-Delphi review. A multi-round review and revision process served to develop seven guidance statements., Results: The final round of review was highly favorable with 99 % overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (mg/dL or mg/L) for the clinical laboratory that is being used., Conclusion: Confirmation of inflammation should be guided by clinical judgement based upon underlying diagnosis or condition, clinical signs, or CRP., Competing Interests: Conflicts of interest M. Isabel T. D. Correia reported support from Abbott, Danone, Fresenius, Nestlé for lectures and educational materials. David Evans disclosed support from Abbott Nutrition for research grants, and consulting and speaking honoraria; Fresenius Kabi for consulting and speaking honoraria; Coram/CVS Optioncare for consulting and speaking honoraria; and Alcresta Therapeutics for consulting and speaking honoraria. M. Cristina Gonzalez disclosed receiving honoraria and/or paid consultancy from Abbott Nutrition, Nutricia, and Nestle Health Science Brazil. Steven Heymsfield reported serving on the medical advisory boards of Tanita Corporation, Medifast, Abbott, and Novo Nordisk. Ainsley Malone disclosed that she is an employee of ASPEN and that she has received an honorarium from the Abbott Nutrition Health Institute. Kris M. Mogensen disclosed serving on the Baxter Advisory Board for parenteral nutrition and indirect calorimetry. Alison Steiber reported that she is an employee of the Academy of Nutrition and Dietetics and that she has received grant funding from the Academy of Nutrition and Dietetics Foundation and the Administration for Community Living. All other authors reported no disclosures., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: To describe the role of Tryptophan (Trp) metabolism and Kynurenine (Kyn) metabolites in nutritional and metabolic changes in cancer., Recent Findings: Trp is in part utilized for protein and neurotransmitters biosynthesis, but more than 95% is implicated in Kyn pathways. In this molecular cascade, metabolites are produced with distinct biological activities regulating the immune response and neurotransmission with potential implications in malnutrition/cachexia during cancer. Immune dysfunction is a phenomenon occurring during cancer and malnutrition. Kyn metabolites regulate lymphocytes activity and recent data in animals showed that the inhibition of indoleamine-2,3-dioxygenase (IDO) via 1-methyl-tryptophan determines partial amelioration of inflammation, but no positive effects on the preservation of muscularity were observed. Kynurenines seem to contribute to muscle catabolism via NAD+ biosynthesis and ROS generation. Trp metabolism via the serotonin biosynthesis is involved in appetite control in cancer. Moreover, kynurenines have a role in determining fatigue in conditions associated with inflammation., Summary: Trp metabolism has implications in immune and energy balance in cancer. The modulation of Trp and kynurenines have impact on central nervous system mechanisms, including appetite, fatigue, and muscle wasting/cachexia. Research focusing on these clinical implications will open new scenario for therapeutic interventions aimed at counteracting nutritional derangements in cancer., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

There is still little information regarding the long-term safety of the vaccines. We report a case of new-onset adult-onset Still's disease (AOSD) that occurred following Covid-19 vaccination. This patient went to the emergency room with dyspnea from the last two weeks and bilateral swellings that occurred several weeks after the first vaccination. Based on the symptoms and laboratory results, we suspected AOSD. Considering the time relationship between Covid-19 vaccination and AOSD onset in our patient, and possible mechanisms linking vaccination with the onset of autoimmune disorders, physicians should consider adverse events from Covid-19 vaccination and assess the benefits and risks of vaccination for each patient., (© 2023. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: Renal Resistive Index (RRI) is an important and non-invasive parameter of renal damage and it is associated with abnormal microcirculation or to a parenchymal injury. The aim of our study was to compare the RRI in a cohort of patients with renal diseases categorized in three groups: nephrotic syndrome (NS), acute nephritic syndrome (ANS) and patients with urinary abnormalities (UA)., Methods: Four hundred eighty-two patients with median age of 48 years (IQR 34-62) with indications for kidney disease were included in the study. Biochemical analyses, clinical assessment with detection of NS, ANS and UA and comorbidities were reported. Renal Doppler ultrasound with RRI was evaluated in all patients at the time of enrolment., Results: NS was present in 81 (16.8 %) patients while ANS in 81 (16.8 %) and UA in 228 (47.3 %) patients. Patients with ANS showed significant higher RRI compared to both patients with NS [0.71 (IQR 0.67-0.78) vs 0.68 (0.63-0.73), p < 0.001] and UA [0.71 (0.67-0.78) vs 0.65 (0.61-0.71), p < 0.001]; RRI was higher in NS patients than in patients with UA [0.68 (0.63-0.73) vs 0.65 (0.61-0.71), p < 0.001]. Patients with ANS had significantly lower median estimated glomerular filtration rate (eGFR) compared respectively to NS and UA patients [19.7 ml/min vs 54.8 ml/min and vs 72.3 ml/min, p < 0.001], while renal length was significantly higher in patients with NS compared to both patients with ANS and UA [111.88 mm vs 101.98 mm and vs 106.15, p < 0.001]. Patients with ANS had more frequently hematuria and RRI ≥ 0.70 (p < 0.001) compared to both patients with NS and patients with UA. The multiple regression analysis, weighted for age, showed that RRI inversely correlates with eGFR (β coefficient = -0.430, p < 0.001)., Conclusions: Higher and pathological RRI were found in ANS than NS and UA. Renal resistive index in ANS reflects changes in intrarenal perfusion and microvascular dysfunction related to disease characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: High CHA 2 DS 2 -VASc score (Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65-74 and Sex category) was associated with adverse clinical outcomes in different settings. The aim of the present study was to evaluate the association between CHA 2 DS 2 -VASc score and R 2 CHA 2 DS 2 -VASc score (which includes renal impairment) with in-hospital mortality and length of hospital stay in patients hospitalized in an internal medicine ward., Methods: We enrolled 983 consecutive patients admitted during 3 years in an internal medicine ward. R 2 CHA 2 DS 2 -VASc score was calculated by adding 2 points to CHA 2 DS 2 -VASc for the presence of chronic kidney disease (CKD), defined according to K-DOQI. The primary outcome was a composite of all-cause mortality and length of hospital stay > 10 days., Results: Patients with CKD stages 3-5 presented with increased CHA 2 DS 2 -VASc vs stages 1-2 (p < 0.001). The composite outcome occurred in 47.3% of inpatients. Multivariable linear logistic regression analyses adjusted for presence of infectious diseases and cancer, with the occurrence of composite outcome showed an adjusted OR of 1.349 (95% CI 1.248-1.462) and 1.254 (95% CI 1.179-1.336) for CHA 2 DS 2 -VASc and R 2 CHA 2 DS 2 -VASc scores, respectively. No differences were found in the association between CHA 2 DS 2 -VASc and R 2 CHA 2 DS 2 -VASc scores with the composite outcome (AUC 0.631 vs 0.630), and furthermore, adding the presence/absence of infectious diseases during hospitalization and positive cancer history to the models increased the AUC (0.667 and 0.663)., Conclusions: Incrementally higher CHA 2 DS 2 -VASc score is associated with increased length of hospital stay and mortality in patients hospitalized in an internal medicine ward, regardless of the presence of CKD., (© 2023. The Author(s).)

Background: The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation., Methods: A GLIM-constituted working group with 36 participants developed consensus-based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements., Results: The final round of review was highly favorable, with 99% overall "agree" or "strongly agree" responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C-reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used., Conclusion: Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP., (© 2024 The Author(s). Published by Elsevier Limited on behalf of European Society for Clinical Nutrition and Metabolism and Elsevier Ltd and Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: Adipose tissue metabolism may be impaired in patients with cancer. In particular, increased lipolysis was described in cancer-promoting adipose tissue atrophy. For this reason, we assessed the expression of the lipolysis-associated genes and proteins in subcutaneous adipose tissue (SAT) of gastrointestinal (GI) cancer patients compared to controls to verify their involvement in cancer, among different types of GI cancers, and in cachexia., Methods: We considered patients with GI cancer (gastric, pancreatic, and colorectal) at their first diagnosis, with/without cachexia, and controls with benign diseases. We collected SAT and total RNA was extracted and ATGL, HSL, PPARα, and MCP1 were analyzed by qRT-PCR. Western blot was performed to evaluate CGI-58, PLIN1 and PLIN5., Results: We found higher expression of ATGL and HSL in GI cancer patients with respect to controls (p ≤ 0.008) and a trend of increase for PPARα (p = 0.055). We found an upregulation of ATGL in GI cancer patients with cachexia (p = 0.033) and without cachexia (p = 0.017) vs controls. HSL was higher in patients with cachexia (p = 0.020) and without cachexia (p = 0.021), compared to controls. ATGL was upregulated in gastric cancer vs controls (p = 0.014) and higher HSL was found in gastric (p = 0.008) and in pancreatic cancer (p = 0.033) vs controls. At the protein level, we found higher CGI-58 in cancer vs controls (p = 0.019) and in cachectic vs controls (p = 0.029), as well as in gastric cancer vs controls (p = 0.027)., Conclusion: In our cohort of GI cancer patients, we found a modulation in the expression of genes and proteins involved in lipolysis, and differences were interestingly detected according to cancer type., (© 2023. The Author(s).)

Background: Small non-coding (snc)RNAs, including microRNAs and P-element induced wimpy testis (PIWI)-interacting-RNAs (piRNAs), crucially regulate gene expression in both physiological and pathological conditions. In particular, some muscle-specific microRNAs (myomiRs) have been involved in the pathogenesis of cancer-induced muscle wasting. The aims of the present study were (i) to profile sncRNAs in both skeletal muscle and plasma of gastrointestinal cancer patients and (ii) to investigate the association among differentially expressed sncRNAs and the level of muscularity at body composition analysis., Methods: Surgical patients with gastrointestinal cancer or benign disease were recruited. Blood samples and muscle biopsies (rectus abdominis) were collected during surgery. Low muscularity patients were those at the lowest tertile of skeletal muscle index (SMI; CT-scan), whereas moderate/high muscularity patients were in the middle and highest SMI tertiles. SncRNAs in the muscle were assessed by RNAseq, circulating microRNAs were evaluated by qPCR., Results: Cancer patients (n = 25; 13 females, 52%) showed a mean age of 71.6 ± 11.2 years, a median body weight loss of 4.2% and a mean BMI of 27.0 ± 3.2 kg/m 2 . Control group (n = 15; 9 females, 60%) showed a mean age 58.1 ± 13.9 years and a mean BMI of 28.0 ± 4.3 kg/m 2 . In cancer patients, the median L3-SMI (cm 2 /m 2 ) was 42.52 (34.42; 49.07). Males showed a median L3-SMI of 46.08 (41.17-51.79) and females a median L3-SMI of 40.77 (33.73-42.87). Moderate-high and low muscularity groups included 17 and 8 patients, respectively. As for circulating microRNAs, miR-21-5p and miR-133a-3p were up-regulated in patients compared with controls, whereas miR-15b-5p resulted down-regulated in the same comparison (about 30% of control values). Sample clustering by muscularity and sex revealed increased miR-133a-3p and miR-206 only in moderate-high muscularity males. SncRNA profiling in the muscle identified 373 microRNAs and 190 piRNAs (72.5% and 18.7% of raw reads, respectively). As for microRNAs, 10 were up-regulated, and 56 were down-regulated in cancer patients versus controls. Among the 24 dysregulated piRNAs, the majority were down-regulated, including the top two most expressed piRNAs in the muscle (piR-12790 and piR-2106). Network analysis on validated mRNA targets of down-regulated microRNAs revealed miR-15b-5p, miR-106a-5p and miR-106b-5p as main interactors of genes related to ubiquitin ligase/transferase activities., Conclusions: These results show dysregulation of both muscle microRNAs and piRNAs in cancer patients compared with controls, the former following a sex-specific pattern. Changes in circulating microRNAs are associated with the degree of muscularity rather than body weight loss., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose: Renin-angiotensin system hyperactivation in autosomal-dominant polycystic kidney disease (ADPKD) patients leads to early hypertension. Cystic enlargement probably causes parenchymal hypoxia, renin secretion, and endothelial dysfunction. Sympathetic and parasympathetic balance is altered in this condition, especially during the night, also affecting blood pressure circadian rhythm. Aim of this study was to evaluate sympathetic/parasympathetic balance using heart rate variability (HRV) parameters and find a correlation between HRV and renal damage progression, as total kidney volume enlargement, in ADPKD patients., Methods: Sixteen adult ADPKD patients were enrolled in the study. Eleven patients (68.8%) were male, and the median age was 42 years (IQR 36-47.5). HRV parameters were calculated using 24 h-ECG Holter. A kidney magnetic resonance imaging (MRI) scan 3 Tesla was performed to evaluate total kidney volume (TKV) and total fibrotic volume (TFV)., Results: A statistically significant positive linear correlation was observed between length of kidneys and frequency domain parameters as low frequency (LF) (r = 0.595, p < 0.05) and LFday (r = 0.587, p < 0.05). Moreover, a statistically significant positive linear correlation exists between high frequency (HF) and TFV (r = 0.804, p < 0.01) or height-adjusted (ha) TFV (r = 0.801, p < 0.01). Finally, we found a statistically significant positive linear correlation between HFnight and TKV (r = 0.608, p < 0.05), ha-TKV (r = 0.685, p < 0.01), TFV (r = 0.594, p < 0.05), and ha-TFV (r = 0.615, p < 0.05)., Conclusion: We suppose that the increase in TKV and TFV could lead to a parasympathetic tone hyperactivation, probably in response to hypoxic stress and vasoconstriction due to cystic enlargement., (© 2023. The Author(s).)

Alterations in the central nervous system in cancer patients are pivotal in determining appetite dysregulation and body weight loss (BWL). Autonomic nervous system activity was tested by measuring heart rate variability (HRV) in cancer patients presenting with anorexia. We considered inpatients with different types of cancer and investigated anorexia using their FAACT scores. HRV was evaluated by a three-channel Holter ECG. The domains of low frequencies (LF, sympathetic activity) and high frequencies (HF, parasympathetic activity) were calculated. Also, SDNN (autonomic activity) and RMSSD (parasympathetic activity) were assessed. We enrolled 56 patients with cancer and 23 controls. In cancer patients, RMSSD and SDNN were lower than in controls ( p < 0.001 and p = 0.009). Sympathetic activity (LF nu) was lower in cancer patients than in controls ( p = 0.023), including sympathovagal balance (LF/HF nu ratio) ( p = 0.025). RMSSD was reduced in anorexic ( p < 0.001) and non-anorexic ( p = 0.003) cancer patients compared to controls. The SDNN was lower in anorexic cancer patients than in non-anorexic cancer patients ( p = 0.025), and it was lower in anorexic cancer patients than in controls ( p = 0.001). LF nu was lower in anorexic cancer patients than in controls ( p = 0.015), as was LF/HF ( p = 0.031). SDNN was negatively correlated with BWL in the cancer group (rho = -0.40; p = 0.007). Our data support the hypothesis that autonomic nervous system dysregulation exists in patients with cancer presenting with anorexia, with implications for its diagnosis and treatment.

Introduction: Resistant hypertension (RH) is characterized by the failure to reach a goal blood pressure despite the administration of three medications at maximally tolerated doses, one of which being a diuretic. RH can be observed in a variety of clinical conditions, such as heart failure and reduced renal function and may confer high cardiovascular risk., Aim: To evaluate the prevalence of RH and its association with clinical outcomes; the primary outcome was in-hospital mortality and the composite outcome was all-cause of mortality and morbidity in a cohort of patients with cardiorenal multimorbidity hospitalized in an internal medicine ward., Methods: We conducted a retrospective analysis of consecutive hypertensive patients with cardiorenal multimorbidity. The composite outcome incorporated all-cause of in-hospital mortality and occurrence of sepsis, pulmonary embolism, acute coronary syndrome, stroke and renal replacement therapy., Results: We collected data in 141 inpatients with a mean age of 77 years ± 10 (males 65.9 %), estimated glomerular filtration rate of 34 ± 18.6 ml/min with length of stay of 17 ± 12 days. The prevalence of RH was 52.4%. In-hospital mortality was observed in 24 patients (17%) and the composite outcome occurred in 87 patients (61.7%) and among these 74 (85.1%) were patients with RH. Free survival for composite outcome was significantly higher in patients without RH than patients with RH (log rank 7.52, p = 0.006). Resistant hypertension was a risk factor for composite outcome [HR 1.857(C.I. 1.170-2.946, p = 0.009)]., Conclusion: In patients with cardiorenal multimorbidity there is a high proportion of RH that represents a risk factor for composite outcome but not for in-hospital mortality., (© 2023. The Author(s).)

Background: Malnutrition is a well-known risk factor for morbidity and mortality in many clinical settings and only few studies assessed the role of malnutrition on systemic sclerosis (SSc) patients' outcomes. The aim of this retrospective study was to evaluate the role of malnutrition as a predictive risk factor for mortality and/or hospitalization in SSc patients during a 4-year follow-up., Methods: One hundred and one SSc patients were included in the study. Biochemical analyses, disease activity index, disease severity scale and anthropometric data were recorded at enrollment. Malnutrition was assessed by the Global Leadership Initiative on Malnutrition (GLIM) criteria., Results: Malnutrition according to GLIM criteria was found in 22 patients (21.8%). During a 4-year follow-up, 20 (19.8%) SSc patients died or were hospitalized for all causes and 11 of them (55.0%) were malnourished. Kaplan-Meier curves showed that event free-survival for composite end-point of mortality and risk of hospitalization was significantly shorter in malnourished than in non-malnourished patients (p<0.001). The survival probability at 4 years was 0.885 (95% CI=0.818-0.959) in the non-malnourished group and 0.500 (95% CI=0.329-0.759) in the malnourished group (p<0.001). In multivariate analysis, malnutrition [HR=4.380 (95% CI=1.706-11.243), p = 0.002] was the most significant predictive risk factor for the composite end-point. Also, female gender [HR=0.157 (95% CI=0.055-0.449), p<0.001], age [HR=1.0450 (95% CI=1.011-1.090), p = 0.012] and disease severity scale [HR=1.269 (95% CI=1.089-1.479), p = 0.002] were predictive factors for the composite end-point., Conclusions: Malnutrition according to GLIM criteria represents a significant predictive risk factor for composite end-point of mortality and risk of hospitalization in SSc patients., Competing Interests: Declaration of Competing of Interest None., (Copyright © 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)