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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 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., (© 2024. The Author(s).)

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).)

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.)

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.)

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).)

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).)

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.)

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.)

Nephroangiosclerosis (NAS) associated with hypertension continues to be one of the most causes of end stage renal diseases in Europe, but it is still poorly studied. The prevalence of NAS shows a large variability due to the difference among different countries regarding clinical presentations and the indication to perform renal biopsy. The study aimed to investigate the prevalence in biopsy-proven NAS patients and the association with hypertension and/or glomerulonephritis (GN). We included all patients referred for native kidney biopsy between 2003-2021 at Policlinic Umberto I of Rome. From 837 patients who underwent renal biopsy NAS was diagnosed in 80 (10.5%) patients. Serum creatinine was significantly higher in NAS [2.07 mg/dl (IQR 1.13-5.2) vs 1.1 mg/dl (IQR 0.8-2.1), p < 0.001] compared to patients without NAS. Hypertension was present in 45% of patients with NAS. Proteinuria was significantly higher in patients with mild-moderate NAS compared to patients with severe NAS [2.6 g/die (IQR 1-5) vs 1.5 g/die (IQR 0.86-2.3), p < 0.05]. We did not find any significant differences, including histological features, between NAS patients with hypertension and NAS patients without hypertension (p > 0.05). IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy were the most frequent GN associated. In conclusion no specific histological features are reported in NAS with and without hypertension. More information on the phenotype, clinical presentation and markers are needed to improve histological and clinical diagnostics., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

In 2010, the definition of cachexia was jointly developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) "Cachexia-anorexia in chronic wasting diseases" and "Nutrition in geriatrics". Cachexia was considered as a synonym of disease-related malnutrition (DRM) with inflammation by the ESPEN guidelines on definitions and terminology of clinical nutrition. Starting from these concepts and taking into account the available evidence the SIG "Cachexia-anorexia in chronic wasting diseases" conducted several meetings throughout 2020-2022 to discuss the similarities and differences between cachexia and DRM, the role of inflammation in DRM, and how it can be assessed. Moreover, in line with the Global Leadership Initiative on Malnutrition (GLIM) framework, in the future the SIG proposes to develop a prediction score to quantify the individual and combined effect(s) of multiple muscle and fat catabolic mechanisms, reduced food intake or assimilation and inflammation, which variably contribute to the cachectic/malnourished phenotype. This DRM/cachexia risk prediction score could consider the factors related to the direct mechanisms of muscle catabolism separately from those related to the reduction of nutrient intake and assimilation. Novel perspectives in the field of DRM with inflammation and cachexia were identified and described in the report., Competing Interests: Conflict of interest S.S. declares the following: Grants or contracts from B. Braun and Nestlé Health Science; Consulting fees from Axium mTech, Nestlé Health Science and Pfizer; Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Axium mTech, Cardinal Health, Amgen, Grand Fontaine, Homeperf, Nestlé Health Science, Nutricia, Theradial; Support for attending meetings and/or travel from Biocodex; Participation on a Data Safety Monitoring Board or Advisory Board from Baxter; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid ESPEN (as Treasurer) and SFNCM (as Vice-President). R.B. declares the following: Participation on Advisory Board member, project UNITE ASUGI 2.0 (diabetes and cardiovascular risk), Novo Nordisk and Advisory Board member: “Focus on Obesity” meeting, Pfizer. The other authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: SARS-CoV-2 causes acute respiratory disease, interstitial and alveolar pneumonia, and involves numerous organs and systems such as the kidney, heart, digestive tract, blood, and nervous system. We aimed to evaluate the incidence of renal manifestations in patients diagnosed with COVID-19 infection., Patients and Methods: We performed a monocentric, cross-sectional, observational study, conducted on 114 patients with SARS-CoV-2. Clinical and laboratory parameters [renal function, serum electrolytes, inflammatory state, blood gas analysis, Interleukin 6 (IL-6) and urinalysis] were evaluated. The same values were checked out after two months (T1), however after negativization., Results: We enrolled 114 patients (59 males) with a mean age of 63.8 ± 13.9 years. We found hematuria in 48 patients (55.8%), proteinuria in 33 patients (38.4%), leukocyturia in 61 patients (70.9%), acute kidney injury (AKI) in 28 patients (24.6%), AKI in chronic kidney disease (CKD) in 24 patients (21.1%). Moreover, we found a significant increase of inflammatory indexes as C Reactive Protein (CRP), lactic dehydrogenase (LDH), alpha 1 and alpha 2 globulins with a subsequent reduction at T1 (p = 0.016, p < 0.001, p = 0.005, p = 0.007; respectively). Hemoglobin and erythrocyte values significantly decreased (p < 0.001, p = 0.003, respectively), and we found lymphopenia (p < 0.001). Also, we found elevated levels of the D-Dimer (p < 0.001) and a significant increase in the International Normalized Ratio (INR) (p = 0.038). We also showed a significant improvement after negativization in oxygen partial pressure (p = 0.001) and oxygen saturation (p < 0.001) and a significant increase in pH (p = 0.018) and bicarbonate concentration (p = 0.042). Moreover, we found a significant increase in IL-6 (p = 0.004). Also, we reported mild hyponatremia and hypokalemia with subsequent significant recovery (p < 0.001, p < 0.001, respectively) and mild hypochloremia with a recovery to the limits of statistical significance (p = 0.053). At the entrance, we found an increase in serum glucose with a significant reduction during recovery (p < 0.001)., Conclusions: The prevalence of AKI and/or CKD and/or abnormal urinalysis in patients diagnosed with COVID-19 on admission seems to be high and appears as a negative prognostic factor. Urinalysis appears to be very useful in unveiling the potential kidney impairment of COVID-19 patients; therefore, urinalysis could be used to reflect and predict the disease severity. We also recommend a careful evaluation of metabolic alterations, inflammatory states, and electrolytic disorders in COVID-19 patients.

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients' outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, treatment toxicity, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients ( p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients ( p < 0.001). Multivariate analysis confirmed that baseline malnutrition ( p = 0.004) and VAS score for appetite loss ( p = 0.0104), in addition to albumin < 35 g/L ( p < 0.0001) and neutrophil/lymphocyte ratio > 3 ( p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.

Background: Sarcopenia is a well know prognostic factor in oncology, influencing patients' quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes., Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints., Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆&#95;SMI-L3, ∆&#95;psoas, and ∆&#95;long spine muscle when they ranged from ~10-20% up to ~45-55%. Greater survival chances were matched by patients achieving a wider ∆&#95;SMI-L3, ∆&#95;abdominal and ∆&#95;long spine muscle., Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes.

Purpose of Review: To describe the role of the main changes occurring in adipose tissue during cachexia and how these affects patient's outcomes, with a specific focus on cancer., Recent Findings: In cachexia, the changes within the adipose tissue have been recently described as the presence of inflammatory infiltration (T-lymphocytes and macrophages), enhanced fibrosis, and the occurrence of beige adipocytes (i.e., browning). The latter one is a process driving cachexia enhancing thermogenesis, primarily via modulation of uncoupling protein 1. Also, increased lipolysis of white adipose tissue, especially in cancer, via higher expression of hormone sensible and adipose tissue triglyceride lipases, was detected in experimental models and in human adipose tissue. Other systemic metabolic alterations occur in association with changes in adiposity, including insulin resistance and increased inflammation, all conditions associated with a worse outcome. Moreover, these profound metabolic alterations were shown to be implicated in several consequences, including extreme and progressive unvoluntary body weight loss., Summary: Alterations in adiposity occur early during cachexia. Adipose tissue atrophy, as well as metabolic changes of white adipose tissues were observed to be pivotal in cachexia, and to be implicated in several clinical complications and poor prognosis.Further research is necessary to clarify the mechanisms underlying the loss of adiposity and therefore to identify novel therapeutic options to counteract this phenomenon in cachexia., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Cachexia is a life-threatening disorder affecting an estimated 50-80% of cancer patients. The loss of skeletal muscle mass in patients with cachexia is associated with an increased risk of anticancer treatment toxicity, surgical complications and reduced response. Despite international guidelines, the identification and management of cancer cachexia remains a significant unmet need owing in part to the lack of routine screening for malnutrition and suboptimal integration of nutrition and metabolic care into clinical oncology practice. In June 2020, Sharing Progress in Cancer Care (SPCC) convened a multidisciplinary task force of medical experts and patient advocates to examine the barriers preventing the timely recognition of cancer cachexia, and provide practical recommendations to improve clinical care. This position paper summarises the key points and highlights available resources to support the integration of structured nutrition care pathways., Competing Interests: Competing Interests JA has received honoraria from Baxter, Berg-Apotheke, Falk, Fresenius Kabi, and Nutricia. SA has received research support from Abbott Vascular and Vifor International for performing investigator-initiated clinical trials, and fees for consultancy and/or speaking from Actimed, Astra‐Zeneca, Bayer, Bioventrix, Boehringer Ingelheim, Brahms, Cardiac Dimensions, Impulse Dynamics, Janssen, Novartis, Respicardia, Servier, V-Wave, and Vifor International. PB has received honoraria for advisory board or conferences from Merck, Sanofi, Merck Sharp & Dohme, Sun Pharma, Angelini, Molteni, Bristol-Myers Squibb, Helsinn, and GSK. SB has received honoraria from Merck, Pfizer, Helsinn, and Angelini; travel accommodations/expenses from Angelini; and advisory/consultancy fees from Helsinn and Angelini. FS reports institutional unrestricted industry grants for clinical research from Helsinn, Celgene, and Fresenius Kabi, and institutional funding for advisory boards or expert panels from Danone, Grünenthal, Helsinn, ISIS Global, Mundipharma, Novartis, Novelpharm, Obexia, Ono Pharmaceutical, Psioxus Therapeutics, PrIME Oncology, Sunstone Captial, and Vifor. MA is, or has been, a consultant for Accord Pharmaceuticals, Amgen, BMS, Celgene, Clinigen Group, Daiichi Sankyo, Eisai Co., Ltd, Eli Lilly, Genomic Health (Exact Sciences), G1 Therapeutics, Inc., GlaxoSmithKline (GSK), Helsinn Healthcare SA, Hospira (Pfizer), Johnson & Johnson, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro (GSK), Teva Pharmaceuticals Industries Ltd., and Vifor Pharma., and received honoraria for lectures at symposia of Accord Pharmaceuticals, Amgen, Astellas, Bayer HealthCare Pharmaceuticals (Schering), Biocon, Boeringer Ingelheim, Cephalon, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Dr Reddy's Laboratories, Genomic Health (Exact Sciences), Glenmark Pharmaceuticals Limited., GSK, Helsinn Healthcare SA, Hospira (Pfizer), Ipsen, Janssen Biotech, Kyowa Kirin Group, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro (GSK), Taiho Pharmaceutical, Teva Pharmaceutical Industries Ltd., and Vifor Pharma. MM, RA, RB, JB, SG, and ZK declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Accumulating scientific evidence supports the benefits of parenteral nutrition (PN) with fish oil (FO) containing intravenous lipid emulsions (ILEs) on clinical outcomes. Yet, the question of the most effective ILE remains controversial. We conducted a network meta-analysis (NMA) to compare and rank different types of ILEs in terms of their effects on infections, sepsis, ICU and hospital length of stay, and in-hospital mortality in adult patients., Methods: MEDLINE, EMBASE, and Web of Science databases were searched for randomized controlled trials (RCTs) published up to May 2022, investigating ILEs as a part of part of PN covering at least 70% of total energy provision. Lipid emulsions were classified in four categories: FO-ILEs, olive oil (OO)-ILEs, medium-chain triglyceride (MCT)/soybean oil (SO)-ILEs, and pure SO-ILEs. Data were statistically combined through Bayesian NMA and the Surface Under the Cumulative RAnking (SUCRA) was calculated for all outcomes., Results: 1651 publications were retrieved in the original search, 47 RCTs were included in the NMA. For FO-ILEs, very highly credible reductions in infection risk versus SO-ILEs [odds ratio (OR) = 0.43 90% credibility interval (CrI) (0.29-0.63)], MCT/soybean oil-ILEs [0.59 (0.43-0.82)], and OO-ILEs [0.56 (0.33-0.91)], and in sepsis risk versus SO-ILEs [0.22 (0.08-0.59)], as well as substantial reductions in hospital length of stay versus SO-ILEs [mean difference (MD) = -2.31 (-3.14 to -1.59) days] and MCT/SO-ILEs (-2.01 (-2.82 to -1.22 days) were shown. According to SUCRA score, FO-ILEs were ranked first for all five outcomes., Conclusions: In hospitalized patients, FO-ILEs provide significant clinical benefits over all other types of ILEs, ranking first for all outcomes investigated., Registration No: PROSPERO 2022 CRD42022328660., Competing Interests: Conflict of interest L. Pradelli is a director and employee of AdRes, which has received project funding from Fresenius Kabi. K. Mayer has received fees from Abbott, AstraZeneca, Baxter, BBraun, Fresenius Kabi, MSD, Nestlé, Novartis, and Pfizer. S. Klek has received speaker’s honoraria from Baxter, Braun, Fresenius Kabi, Nestlé, Nutricia, Shire, and Vipharm and acted as an advisory board member for Fresenius Kabi, Shire, and Tracheron. M. Rosenthal has received fees from Fresenius, Nestle, and Abbott. M. Povero is an employee of AdRes, which has received project funding from Fresenius Kabi. A. R. Heller has received project funding from Fresenius Kabi. M. Muscaritoli has received speaker’s fees from Fresenius Kabi., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

(1) Background: We investigated, for the first time, whether dietary simple sugar intake affects MELD score changes over time in a cohort of cirrhotic liver transplant candidates. (2) Methods: the MELD score, dietary habits using a 3-day food diary, and visceral adipose tissue index (VATI) measured with CT scan were assessed in 80 consecutive outpatient cirrhotic patients at baseline, after counseling to follow current nutritional guidelines. The MELD score was reassessed after six months and the DELTA-MELD was calculated as the MELD at the second assessment minus the MELD at baseline. (3) Results: Compared with the baseline, the MELD score of cirrhotic patients at the end of the study was decreased, stable, or increased in 36%, 8% and 56% of patients, respectively. In separate multiple linear regression models, DELTA-MELD was positively and independently correlated with the daily intake of simple sugars expressed in g/kg body weight ( p = 0.01) or as a percentage of total caloric intake ( p = 0.0004) and with the number of daily portions of fruit, added sugar, jam, and honey ( p = 0.003). These associations were present almost exclusively in patients with VATI above the median value. (4) Conclusions: In cirrhotic patients with high amounts of visceral adipose tissue the consumption of simple sugars and fructose should be limited to improve their clinical outcome.

Objective: In this study, we aimed to evaluate the kidney involvement assessed by estimated glomerular filtration rate (eGFR), the associations with specific clinical disease variables and laboratory findings, and the predictive role of eGFR on clinical outcomes of patients admitted with COVID-19 in Internal Medicine ward in the first wave., Patients and Methods: Clinical data of 162 consecutive patients hospitalized in the University Hospital Policlinico Umberto I in Rome, Italy, between December 2020 to May 2021 were collected and retrospectively analyzed., Results: The median eGFR was significantly lower in patients with worse outcomes than in patients with favorable outcomes [56.64 ml/min/1.73 m2 (IQR 32.27-89.73) vs. 83.39 ml/min/1.73 m2 (IQR 69.59-97.08), p<0.001]. Patients with eGFR < 60 ml/min/1.73 m2 (n=38) were significantly older compared to patients with normal eGFR [82 years (IQR 74-90) vs. 61 years (IQR 53-74), p<0.001] and they had fever less frequently [39.5% vs. 64.2%, p<0.01]. Kaplan-Meier curves demonstrated that overall survival was significantly shorter in patients with eGFR < 60 ml/min/1.73 m2 (p<0.001). In multivariate analysis, only eGFR < 60 ml/min/1.73 m2 [HR=2.915 (95% CI=1.110-7.659), p<0.05] and platelet to lymphocyte ratio [HR=1.004 (95% CI=1.002-1.007), p<0.01] showed a significant predictive value for death or transfer to intensive care unit (ICU)., Conclusions: Kidney involvement on admission was an independent predictor for death or transfer to ICU among hospitalized COVID-19 patients. The presence of chronic kidney disease could be regarded as a relevant factor in risk stratification for COVID-19.

Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by microvascular damage and fibrosis of the skin and internal organs. Among SSc complications, changes in nutritional status have a negative effect on quality of life and predispose patients to malnutrition. The aim of this exploratory pilot study was to examine whether bioelectrical impedance analysis-derived phase angle (PhA) is a parameter of nutritional status and a marker of mortality in patients with SSc., Methods: Consecutive adult patients with SSc were included in the study. Biochemical analyses, anthropometric data, and bioelectrical impedance analysis assessments were recorded at the time of enrollment. The Malnutrition Universal Screening Tool (MUST) and Global Leadership Initiative on Malnutrition (GLIM) were applied to assess nutritional status., Results: A total of 104 patients with SSc (88 women; median age: 55 y [interquartile range (IQR), 45.5- 66 y]) were enrolled. In patients with SSc and high malnutrition risk according to MUST, mean values of PhA were significantly lower than those of patients with SSc and low malnutrition risk (4° [IQR, 3.7°-4.4°] vs 4.6° [IQR, 4.2°-5.1°]; P = 0.004). Patients with SSc and malnutrition according to the GLIM criteria showed significantly lower PhA than patients with SSc but without malnutrition (3.8° [IQR, 3.5°-4.3°] vs 4.6° [IQR, 4.2°-5.1°]; P < 0.0001). Kaplan-Meier curves demonstrated that overall survival was significantly shorter (34.57 mo [±13.35] vs 48 mo [±0]; P = 0.001) in patients with SSc and PhA <3.75°. In the multivariate analysis, only PhA was a predictive factor for death (hazard ratio: 0.283; 95% confidence interval, 0.083-0.965; P = 0.044)., Conclusions: The data obtained suggest that lower PhA values in patients with SSc are associated with an increased malnutrition risk with MUST, malnutrition with GLIM, and increased mortality. Additional studies are necessary to confirm these preliminary results., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer. 50 HD patients were enrolled, and fatigue was present in 24% of the cohort. Patients with fatigue showed higher Kyn/Trp ( p = 0.005), were older ( p = 0.007), and IL-6 levels resulted higher than in non-fatigue patients ( p < 0.001). HD patients with fatigue showed lower intracellular water (surrogate of muscle mass) ( p < 0.001), as well as lower hand grip strength ( p = 0.02). The Kyn/Trp ratio positively correlated with IL-6 and ECW/ICW ( p = 0.004 and p = 0.014). By logistic regression analysis, higher ICW/h 2 was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity.

The implementation of long-term parenteral nutrition (PN) often requires the placement of central venous access, a procedure that carries a considerable risk of catheter-related venous thrombosis (CRT). The occurrence of CRT represents a major event in the natural history of patients in PN since it can lead to central venous access loss and PN failure. Despite the importance of this topic in clinical nutrition, the prevention and treatment of CRT in PN represents one of the "gray areas" of the literature of the presence of few randomized controlled clinical trials and the generally low level of evidence of published scientific papers. Through a narrative review of the literature and a Delphi consensus, the Italian Society of Clinical Nutrition and Metabolism (SINuC) aimed to collect some practical recommendations regarding the current state-of-the-art in the prevention, diagnosis, and treatment of CRT in patients undergoing long-term PN., 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., (Copyright © 2023 Zaccone, Santoro, Guerrieri, Diblasi, Roncarati, Viticchi, Vecchiarelli, Santoliquido, Fiore, Molfino, Landi, Moroncini, Gasbarrini, Muscaritoli and Falsetti.)

Objective: COVID-19 clinical presentation ranges from asymptomatic infection to an inflammatory cytokine storm with multi-organ failure and fatal outcomes. The identification of high-risk patients for severe disease is crucial to plan an early treatment and intensive follow-up. We aimed to investigate negative prognostic factors in a group of patients hospitalized for COVID-19., Patients and Methods: 181 patients (90 men and 91 women, mean age 66.56 ± 13.53 years) were enrolled. Each patient received a work-up including medical history, clinical examination, arterial blood gas analysis, laboratory blood tests, feasible ventilatory support required during hospital stay, intensive care setting required, duration of illness and length of hospital stay (>or<25 days). For the assessment of the severity of COVID-19, three main indicators were considered: 1) the intensive care unit (ICU) admission 2) the hospitalization length >25 days; 3) the need of non-invasive ventilation (NIV)., Results: The independent risk factor associated with the ICU admission were lactic dehydrogenase elevation (p=0.046), C reactive protein elevation (p=0.014) at hospital admission and direct oral anticoagulant home therapy (p=0.048); for hospital length >25 days: early corticosteroid therapy (p=0.035); for NIV treatment: ferritin elevation at hospital admission (p=0.006)., Conclusions: The presence of the above factors may be useful to identify patients at high risk of developing a severe COVID-19 that need an early treatment and intensive follow-up.

Nutritional issues, including malnutrition, low muscle mass, sarcopenia (i.e., low muscle mass and strength), and cachexia (i.e., weight loss characterized by a continuous decline in skeletal muscle mass, with or without fat loss), are commonly experienced by patients with cancer at all stages of disease. Cancer cachexia may be associated with poor nutritional status and can compromise a patient's ability to tolerate antineoplastic therapy, increase the likelihood of post-surgical complications, and impact long-term outcomes including survival, quality of life, and function. One of the primary nutritional problems these patients experience is malnutrition, of which muscle depletion represents a clinically relevant feature. There have been recent calls for nutritional screening, assessment, treatment, and monitoring as a consistent component of care for all patients diagnosed with cancer. To achieve this, there is a need for a standardized approach to enable oncologists to identify patients commencing and undergoing antineoplastic therapy who are or who may be at risk of malnutrition and/or muscle depletion. This approach should not replace existing tools used in the dietitian's role, but rather give the oncologist a simple nutritional protocol for optimization of the patient care pathway where this is needed. Given the considerable time constraints in day-to-day oncology practice, any such approach must be simple and quick to implement so that oncologists can flag individual patients for further evaluation and follow-up with appropriate members of the multidisciplinary care team. To enable the rapid and routine identification of patients with or at risk of malnutrition and/or muscle depletion, an expert panel of nutrition specialists and practicing oncologists developed the PROtocol for NuTritional risk in Oncology (PRONTO). The protocol enables the rapid identification of patients with or at risk of malnutrition and/or muscle depletion and provides guidance on next steps. The protocol is adaptable to multiple settings and countries, which makes implementation feasible by oncologists and may optimize patient outcomes. We advise the use of this protocol in countries/clinical scenarios where a specialized approach to nutrition assessment and care is not available.

Background: Patients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis., Patients and Methods: Patients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels., Results: Overall, 102 patients [53 male; median age: 67 (range, 21-88) years] were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kg/m 2 ; average percentage of weight loss was 10.1 ± 7.8%. At diagnosis, 68% (69/102) of patients had cachexia, and 11% (11/102) pre-cachexia. Prevalence of anorexia was 57% (58/102) and 75% (76/102) according to FAACT and AQ, respectively. Forty-eight percent (49/102) of patients had hypophagia. Patients with anorexia had lower daily energy ( p = 0.002) and protein intake ( p = 0.0257), and greater percentage of weight loss ( p = 0.0005). In patients with hypophagia, negative correlations were observed between percentage of weight loss and total daily calorie (r = -0.40; p = 0.01) and protein intake (r = -0.340; p = 0.018)., Conclusion: Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed., 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., (Copyright © 2023 Molfino, Emerenziani, Tonini, Santini, Gigante, Guarino, Nuglio, Imbimbo, La Cesa, Cicala and Muscaritoli.)

Background & Aims: Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia., Methods: Genome-wide transcriptomic profiling was assessed in PBMCs RNA from newly diagnosed lung cancer patients and in a control group. RT-qPCR was used for selected genes., Results: RNA-Seq analysis revealed among groups a large number of differentially expressed genes mainly implicated in immune system regulation, oxidative stress and cytokine-mediated inflammation signaling pathways. In particular, we identified a total of 983 DEGs (843 up-regulated; 140 down-regulated) in anorexic cancer compared to controls. A selected number of DEGs including ADAM8, SMAD4, CCR4 and CLU were differentially expressed within cancer group according to the presence/absence of anorexia. In terms of RT-qPCR, ADAM8 was less expressed in cancer patients than controls (p < 0.001), and in anorexic patients vs controls (p = 0.001). The expression of SMAD4 was lower in cancer vs controls (p = 0.005), and in anorexic patients vs controls (p = 0.009). We observed lower CCR4 expression in both anorexic and non-anorexic vs control (p = 0.004, p = 0.011, respectively) and a similar trend was present for CLU., Conclusions: Our data shed new light on the role of specific genes and their associated molecular pathways as potential key mechanisms for the development of anorexia and may represent a novel landmark for understanding the complex pathophysiology of impaired appetite in cancer., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition., (© 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism and American Society for Parenteral and Enteral Nutrition. All rights reserved.)

Background: Digital ulcers (DUs) are one of the main causes of disability among systemic sclerosis (SSc) patients. The inflammation plays a crucial role in mediating the pathophysiological process underlying SSc. Objective of this study was to evaluate Maresin1 (MaR1) serum levels in SSc patients and in healthy controls (HC). Secondary aims were to evaluate the relationship between MaR and diseases variables and to assess the predictive role of MaR1 in the development of new digital ulcers (DUs) during 18 weeks follow-up., Methods: MaR1 serum level was evaluated in 55 SSc patients and 24 HC. In SSc patients, clinical assessment was performed at baseline and after 18 week follow-up by the same-blinded observer on serum MaR1 levels., Results: MaR1 was significantly lower in SSc patients than in HC [367 pg/ml (IQR 304-468.3 pg/ml) vs 467.7 pg/ml (IQR 422-522 pg/ml), p < 0.001]. During follow-up, six patients (10.9%) developed DUs. MaR1 was higher in SSc patients with new DUs than in patients without new DUs [518.2 pg/ml (IQR 468.2-596.5 pg/ml) vs 355 pg/ml (IQR 299.8-444.7 pg/ml), p < 0.01]. Free survival from new DUs is significantly lower in SSc patients with increased MaR1 serum level than in SSc patient with normal MaR1 serum level. In multivariate analysis, serum level of MaR1 > 393.2 pg/ml is a predictive marker for new DUs., Conclusion: In SSc patients, MaR1 is reduced compared to HC and it is a predictive marker of new DUs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Renal resistive index (RRI) measured by Doppler sonography is a marker of microvascular status and it is associated with changes in renal function. Aim of the study was to assess RRI in biopsy-proven tubulointerstitial nephritis (TIN) in patients with and without glomerular disease., Methods: 132 consecutive patients underwent to native renal biopsy with diagnosis of isolated TIN or in association with glomerulonephritis. Estimated glomerular filtration rate (eGFR), 24-hour urinary protein excretion and renal ecocolorDoppler ultrasonography with RRI assessment were performed at time of enrollment., Results: Patients with isolated-TIN had significantly higher RRI than both patients with non-immunoglobulin A glomerulonephritis (non-IgA-TIN) [0.73 (0.68-0.77) vs 0.64 (0.60-0.67), p < 0.001] and patients with IgA nephropathy (IgAN) [0.73 (0.68-0.77) vs 0.66 (0.60-0.71), p < 0.01]. Patients with isolated-TIN had mainly RRI ≥ 0.70 (n = 15, 65.2%) with the respect to patients with non-IgA-TIN (n = 7, 12.3%) and patients with IgAN (n = 17, 32.7%). A negative linear correlation was found between RRI and hemoglobin (r = 0.233, p < 0.01) and between RRI and eGFR (r = 0.537, p < 0.001)., Conclusion: Tubulointerstitial damage is the most accurate histological lesion that correlates with eGFR and renal impairment. RRI can be a useful parameter to detect tubulointerstitial lesions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction/objectives: Gastrointestinal tract (GIT) involvement is frequently observed in systemic sclerosis (SSc) and may lead to nutritional impairment. The aim of the study was to assess the prevalence of symptoms related to GIT involvement and to analyze the possible association between gastrointestinal symptoms and low muscularity in SSc patients., Methods: Sixty-nine consecutive patients (60 females, median age 53 (IQR 43-63), body mass index (BMI) 23.2 (IQR 20.9-24.6) kg/m 2 ) with diagnosis of SSc admitted to our Scleroderma Unit were enrolled. Clinical status, anthropometric data, and bioelectrical impedance (Inbody 770, USA) analysis-assessed Fat-Free Mass Index (FFMI) were recorded upon enrollment. UCLA questionnaire was used to quantify GIT involvement with seven specific scales., Results: Mean FFMI was 16.2 kg/m 2 (IQR 15.2-17.6). The median UCLA total score was 0.53 (IQR 0.19-0.89). FFMI showed a significant negative correlation with UCLA total score (r = -0.29, p = 0.016) and UCLA distention/bloating (r = -0.35, p < 0.01). In 16 patients (23.1%), FFMI was reduced and UCLA distention/bloating was significantly higher (p = 0.039) in SSc patients with lower FFMI [1.75 (IQR 0.75-2.12) vs 0.75 (IQR 0.25-1.75)]. At multiple linear regression model, FFMI showed association with UCLA distention/bloating [beta coefficient - 0.315 (95% CI of beta coefficient: -0.591; -0.039), p = 0.026], BMI [beta coefficient 0.259 (95% CI of beta coefficient: 0.163; 0.355), p = 0.001], and disease duration [beta coefficient - 0.033 (95% CI of beta coefficient: -0.059; -0.007), p = 0.015]., Conclusions: In SSc, low FFMI is associated with symptoms related to GIT involvement, in particular with distension/bloating. Key Points • FFMI is associated with symptoms related to GIT involvement. • Low FFMI is associated with symptoms related to UCLA distention/bloating. • Malnutrition is not associated with symptoms related to GIT involvement., (© 2022. The Author(s).)

The Global Leadership Initiative on Malnutrition (GLIM) provides consensus criteria for the diagnosis of malnutrition that can be widely applied. The GLIM approach is based on the assessment of three phenotypic (weight loss, low body mass index, and low skeletal muscle mass) and two etiologic (low food intake and presence of disease with systemic inflammation) criteria, with diagnosis confirmed by any combination of one phenotypic and one etiologic criterion fulfilled. Assessment of muscle mass is less commonly performed than other phenotypic malnutrition criteria, and its interpretation may be less straightforward, particularly in settings that lack access to skilled clinical nutrition practitioners and/or to body composition methodologies. In order to promote the widespread assessment of skeletal muscle mass as an integral part of the GLIM diagnosis of malnutrition, the GLIM consortium appointed a working group to provide consensus-based guidance on assessment of skeletal muscle mass. When such methods and skills are available, quantitative assessment of muscle mass should be measured or estimated using dual-energy x-ray absorptiometry, computerized tomography, or bioelectrical impedance analysis. For settings where these resources are not available, then the use of anthropometric measures and physical examination are also endorsed. Validated ethnic- and sex-specific cutoff values for each measurement and tool are recommended when available. Measurement of skeletal muscle function is not advised as surrogate measurement of muscle mass. However, once malnutrition is diagnosed, skeletal muscle function should be investigated as a relevant component of sarcopenia and for complete nutrition assessment of persons with malnutrition., Competing Interests: Conflict of interest None declared., (Copyright © 2022 Elsevier Ltd, European Society for Clinical Nutrition and Metabolism, American Society for Parenteral and Enteral Nutrition. Published by Elsevier Ltd.. All rights reserved.)

We assessed the molecular phenotype of the browning of white adipose tissue in newly diagnosed cancer patients and controls undergoing surgery for gastrointestinal tumors and for non-malignant diseases, respectively. We collected subcutaneous adipose tissue (SAT) samples and using RT-PCR, we analyzed the expression of markers of browning and using Western blot the protein levels of UCP1 and PGC1α. The Ucp1 mRNA levels were lower in cancer patients vs. controls ( p = 0.01), whereas Cidea and Tmem26 mRNA levels were higher in cancer patients. We found higher PGC1α protein levels in patients vs. controls, while no differences were seen for UCP1. The Ucp1 expression was lower in cachectic and non-cachectic patients vs. controls, whereas Cidea expression was higher in cachectic and non-cachectic patients vs. controls. Pgc1α mRNA levels were higher in cachectic vs. non-cachectic patients ( p = 0.03) vs. controls ( p = 0.016). According to type of tumors, we did not observe differences in Cidea expression, whereas Pgc1α was higher in pancreatic cancer vs. colorectal and vs. controls. We observed the lower expression of Ucp1 in pancreatic and colorectal cancer vs. controls. We documented higher UCP1 protein levels in pancreatic cancer patients vs. colorectal ( p = 0.002) and vs. controls ( p = 0.031). PGC1α protein levels were higher in pancreatic cancer patients vs. controls. Different markers of the browning of SAT are modulated, and pancreatic cancer showed changes in UCP1 and PGC1α; PGC1α was highly expressed in cachectic patients, with clinical implications that should be further clarified.

Background: Persistent symptoms including dyspnea and functional impairment are common in COVID-19 survivors. Poor muscle quality (myosteatosis) associates with poor short-term outcomes in COVID-19 patients. The aim of this observational study was to assess the relationship between myosteatosis diagnosed during acute COVID-19 and patient-reported outcomes at 6 months after discharge., Methods: Myosteatosis was diagnosed based on CT-derived skeletal muscle radiation attenuation (SM-RA) measured during hospitalization in 97 COVID-19 survivors who had available anthropometric and clinical data upon admission and at the 6-month follow-up after discharge. Dyspnea in daily activities was assessed using the modified Medical Research Council (mMRC) scale for dyspnea. Health-related quality of life was measured using the European quality of life questionnaire three-level version (EQ-5D-3L)., Results: Characteristics of patients with (lowest sex- and age-specific tertile of SM-RA) or without myosteatosis during acute COVID-19 were similar. At 6 months, patients with myosteatosis had greater rates of obesity (48.4 vs. 27.7%, p = 0.046), abdominal obesity (80.0 vs. 47.6%, p = 0.003), dyspnea (32.3 vs. 12.5%, p = 0.021) and mobility problems (32.3 vs. 12.5%, p = 0.004). Myosteatosis diagnosed during acute COVID-19 was the only significant predictor of persistent dyspnea (OR 3.19 [95% C.I. 1.04; 9.87], p = 0.043) and mobility problems (OR 3.70 [95% C.I. 1.25; 10.95], p = 0.018) at 6 months at logistic regression adjusted for sex, age, and BMI., Conclusion: Myosteatosis diagnosed during acute COVID-19 significantly predicts persistent dyspnea and mobility problems at 6 months after hospital discharge independent of age, sex, and body mass., Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT04318366]., 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., (Copyright © 2022 De Lorenzo, Palmisano, Esposito, Gnasso, Nicoletti, Leone, Vignale, Falbo, Ferrante, Cilla, Magnaghi, Martinenghi, Vitali, Molfino, Rovere-Querini, Muscaritoli and Conte.)

Background: During cancer cachexia, several alterations occur in peripheral tissues, and the adipose tissue may be involved during the catabolic state. We aimed at investigating histological rearrangement and infiltration of inflammatory cells in subcutaneous adipose tissue (SAT) of patients with cancer undergoing surgery, according to the presence/absence of cachexia., Methods: We considered gastrointestinal cancer patients and controls with non-malignant diseases undergoing surgery. We collected SAT samples and performed histomorphological analyses [cross-sectional area (CSA) and per cent of fibrosis] and immunohistochemistry to characterize the inflammatory cells. By computed tomography (CT) scan, we calculated SAT and visceral adipose tissue (VAT)., Results: We enrolled 51 participants (31 gastrointestinal cancer patients and 20 controls). In cancer patients, cachexia was present in 13/31 (42%). The CSA (μm 2 ) of the adipocytes from SAT was reduced in cancer patients vs. controls (3148, inter-quartile range 2574-3755 vs. 4474, inter-quartile range 3654-5183) (P < 0.001), in particular in cachectic patients vs. non-cachectic (median 2518 vs. median 3470) (P = 0.03) and in cachectic vs. controls (P < 0.001), as well as in non-cachectic vs. controls (P = 0.04). The median per cent of fibrosis was higher in cancer patients vs. controls (9 vs. 3) (P = 0.0001), in particular in cachectic vs. non-cachectic (13.35 vs. 7.13) (P = 0.03). We observed a higher number of macrophages (CD68) (P = 0.0001) and T lymphocytes (CD3) (P = 0.002) in SAT of cancer patients vs. controls, and the number of T lymphocytes was higher in cachectic vs. non-cachectic patients (P = 0.025). Anorexic cancer patients showed in SAT a higher number of macrophages and T lymphocytes with respect to controls (P < 0.0001), whereas no difference was present between anorexic and non-anorexic patients. At CT scan, cachectic patients showed lower VAT and SAT vs. non-cachectic (VAT: 97.64 ± 40.79 vs. 212.53 ± 79.24, P = 0.0002; SAT: 126.27 ± 87.92 vs. 206.27 ± 61.93, P = 0.01, respectively). Cancer patients with low CSA, high degree of fibrosis, and high number of T lymphocytes presented with lower body mass index and lower SAT and VAT at CT scan (P ≤ 0.01)., Conclusions: We found histological alterations of SAT among gastrointestinal cancer patients and in particular significant changes in CSA, fibrosis, and inflammation when cachexia was present; the changes in histomorphological parameters of the adipocytes reflected alterations in adiposity at body composition analysis., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: Reduced estimated creatinine clearance (eCrCl) is prevalent in older patients and impacts on drug prescription. In this study, the burden of eCrCl reduction and its associated factors and impact on outcomes were analyzed. Moreover, the rate of inappropriate drug prescription according to eCrCl and its impact on outcomes were described., Methods: Data were obtained from "REgistro POliterapie SIMI" (REPOSI), a prospective observational register enrolling hospitalized patients aged ≥ 65 years. Patients enrolled from 2010-2016 with available data to calculate eCrCl according to the Cockcroft-Gault formula were included in this analysis., Results: A total of 5046 patients were available for analysis. Among these, we found an eCrCl of 45-59 mL/min in 1163 patients (23.0%), an eCrCl of 30-44 mL/min in 1128 (22.4%), an eCrCl of 15-29 mL/min in 702 (13.9%), and an eCrCl < 15 mL/min in 152 (3.0%), with several clinical factors associated with decreasing eCrCl. During follow-up, a progressively higher risk for all-cause death, cardiovascular (CV) death, any death/re-hospitalization, and CV death/re-hospitalization was found across the renal function classes. Among patients with hypertension, diabetes mellitus, atrial fibrillation, coronary artery disease, and heart failure, 476 (10.9%) were inappropriately prescribed medications according to eCrCl. During follow-up, inappropriate prescription was associated with increased risk of all-cause death (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.13-1.97) and any death/re-hospitalization (OR 1.30, 95% CI 1.03-1.63)., Conclusions: In older hospitalized patients, impaired eCrCl is prevalent and associated with several factors, polypharmacy in particular. Patients with reduced eCrCl have a higher risk of major clinical outcomes, and > 10% of them are prescribed an inappropriate drug, with a higher risk for major clinical outcomes., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)