Publications by authors named "Alessio Molfino"

93 Publications

Cancer-associated anorexia: Validity and performance overtime of different appetite tools among patients at their first cancer diagnosis.

Clin Nutr 2021 Feb 23. Epub 2021 Feb 23.

Department of Translational and Precision Medicine, Sapienza University of Rome, V.le dell'Università 37, Rome, Italy. Electronic address:

Background & Aims: Anorexia is a frequent symptom in cancer and we aimed to assess its prevalence among patients at their first cancer diagnosis by different appetite tools and the relationship between each tool with self-reports of food intake. We also tested whether cancer anorexia influences outcomes independently of reduced food intake or body weight loss (BWL) overtime and whether BWL was associated with complications during anticancer-therapy.

Methods: Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score, self-assessment of appetite, Anorexia Questionnaire (AQ) and Visual Analog Scale (VAS) were administered. Percent of food intake was used as a criterion measure of anorexia. We registered BWL and anticancer-therapy complications over 3-month-follow-up.

Results: 438 cancer patients from 7 cancer-centers worldwide were included. The prevalence of anorexia was 39.9% by FAACT score, 40.2% by VAS, 40.6% by the self-assessment of appetite and 65.4% by AQ. Low food intake (≤50%) was reported in 28% of patients. All appetite tools correlated with food intake percent (P < 0.0001). We documented a correlation between self-assessment of appetite, FAACT score, VAS and BWL overtime (P < 0.04). The self-assessment of appetite (P = 0.0152) and the FAACT score (P = 0.043) were associated with BWL independently of anticancer therapies. Among patients with BWL, the risk to develop complications was greater with respect to those who maintained a stable or gained body weight (P = 0.03).

Conclusions: In our sample of cancer patients, FAACT score and self-assessment of appetite performed well when low food intake was used as a criterion measure, and revealed an association of anorexia with BWL, which was, in turn, related to the development of anticancer-therapy complications.
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http://dx.doi.org/10.1016/j.clnu.2021.02.016DOI Listing
February 2021

A patient with severe anemia and body weight loss: unveiling what was behind.

Intern Emerg Med 2021 Feb 15. Epub 2021 Feb 15.

Department of Translational and Precision Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy.

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http://dx.doi.org/10.1007/s11739-021-02658-3DOI Listing
February 2021

Association between Growth Differentiation Factor-15 (GDF-15) Serum Levels, Anorexia and Low Muscle Mass among Cancer Patients.

Cancers (Basel) 2020 Dec 31;13(1). Epub 2020 Dec 31.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP ( = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP ( 0.049). The GDF-15 levels were higher in CP vs. controls ( = 0.00016), as well as in anorexic vs. non-anorexic CP ( = 0.005) and vs. controls ( < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP ( = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity.
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http://dx.doi.org/10.3390/cancers13010099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795323PMC
December 2020

Association between Multidimensional Prognostic Index and Hospitalization and Mortality among Older Adults with Chronic Kidney Disease on Conservative or on Replacement Therapy.

J Clin Med 2020 Dec 7;9(12). Epub 2020 Dec 7.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

The prevalence of renal disease is constantly increasing in older adults and a prognostic evaluation by a valid tool may play a key role in treatment management. We aimed to assess the association(s) between the multidimensional prognostic index (MPI) and both the hospitalization and mortality among older adults with renal disease. Patients with chronic kidney disease (CKD) (stage 3-5 KDOQI) and on dialysis were considered. Clinical parameters were registered at baseline and after 2 years. In all the patients, the MPI was calculated and divided into grade 0 (low risk), 1 (moderate risk), and 2 (severe risk). Hospitalizations and mortality were recorded during the follow-up and analyzed according to MPI grade. A total of 173 patients, with a median age of 76 years, on conservative ( = 105) and replacement therapy (32 patients on hemodialysis, 36 patients on peritoneal dialysis) were enrolled. Of them, 60 patients were in MPI grade 0, 102 in grade 1, and 11 in grade 2. The median duration of all the hospitalizations was 6 days and the number of deaths was 33. MPI significantly correlated with days of hospitalization ( = 0.801, < 0.00001) and number of hospitalizations per year ( = 0.808, < 0.00001), which was higher in MPI grade 2 compared to grade 1 ( < 0.001) and to grade 0 ( < 0.001). We found a significant association between MPI grades and mortality ( < 0.001). Our results indicate that MPI was associated with outcomes in patients with renal disease, suggesting that a multidimensional evaluation should be implemented in this clinical setting.
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http://dx.doi.org/10.3390/jcm9123965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762388PMC
December 2020

Locoregional Surgery in Metastatic Breast Cancer: Do Concomitant Metabolic Aspects Have a Role on the Management and Prognosis in this Setting?

J Pers Med 2020 Nov 13;10(4). Epub 2020 Nov 13.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

Although they cannot be considered curative, the new therapeutic integrated advances in metastatic breast cancer (MBC) have substantially improved patient outcomes. Traditionally, surgery was confined to palliation of symptomatic or ulcerating lumps. Data suggest, in some cases, a possible additive role for more aggressive locoregional surgical therapy in combination with systemic treatments in the metastatic setting, although a low level of evidence has been shown in terms of improvement in overall survival in MBC patients treated with surgery and medical treatment compared to medical treatment alone. In this light, tumor heterogeneity remains a challenge. To effectively reshape the therapeutic approach to MBC, careful consideration of who is a good candidate for locoregional resection is paramount. The patient's global health condition, impacting on cancer progression and morbidity and their associated molecular targets, have to be considered in treatment decision-making. In particular, more recently, research has been focused on the role of metabolic derangements, including the presence of metabolic syndrome, which represent well-known conditions related to breast cancer recurrence and distant metastasis and are, therefore, involved in the prognosis. In the present article, we focus on locoregional surgical strategies in MBC and whether concomitant metabolic derangements may have a role in prognosis.
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http://dx.doi.org/10.3390/jpm10040227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712935PMC
November 2020

What Are the Risk Factors for Malnutrition in Older-Aged Institutionalized Adults?

Nutrients 2020 Sep 18;12(9). Epub 2020 Sep 18.

Department of Translational and Precision Medicine, Sapienza University, 00185 Rome, Italy.

Malnutrition is common in older adults and is associated with functional impairment, reduced quality of life, and increased morbidity and mortality. The aim of this study was to explore the association between health (including depression), physical functioning, disability and cognitive decline, and risk of malnutrition. Participants were recruited from nursing homes in Italy and completed a detailed multidimensional geriatric evaluation. All the data analyses were completed using Stata Version 15.1. The study included 246 participants with an age range of 50 to 102 (80.4 ± 10.5). The sample was characterised by a high degree of cognitive and functional impairment, disability, and poor health and nutritional status (according to Mini Nutritional Assessment (MNA), 38.2% were at risk for malnutrition and 19.5% were malnourished). Using a stepwise linear regression model, age (B = -0.043, SE = 0.016, = 0.010), depression (B = -0.133, SE = 0.052, = 0.011), disability (B = 0.517, SE = 0.068, < 0.001), and physical performance (B = -0.191, SE = 0.095, = 0.045) remained significantly associated with the malnutrition risk in the final model (adjusted R-squared = 0.298). The logistic regression model incorporating age, depression, disability, and physical performance was found to have high discriminative accuracy (AUC = 0.747; 95%CI: 0.686 to 0.808) for predicting the risk of malnutrition. The results of the study confirm the need to assess nutritional status and to investigate the presence of risk factors associated with malnutrition in order to achieve effective prevention and plan a better intervention strategy.
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http://dx.doi.org/10.3390/nu12092857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551464PMC
September 2020

Plasma enterobacterial ClpB levels and ClpB- and α-MSH-reactive immunoglobulins in lung cancer patients with and without anorexia.

Nutrition 2020 10 22;78:110952. Epub 2020 Jul 22.

Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine (IRIB), Normandie University, Rouen, France.

Objectives: Anorexia represents a common and debilitating clinical problem in patients with several forms of cancer, in particular lung cancer, but its mechanisms are not completely understood. Recently, the caseinolytic-protease-B (ClpB) homologue protein, produced by common gut bacteria, such as Escherichia coli, was identified as an antigen-mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. ClpB was previously detected in human plasma and displayed satietogenic properties; however, its possible relevance to cancer anorexia has not yet been investigated.

Methods: To address this question, we analyzed plasma ClpB concentrations as well as levels and affinities of anti-ClpB and α-MSH-reactive antibodies in patients with lung cancer with and without anorexia as compared with body mass index-matched healthy controls with normal appetite.

Results: We found that plasma ClpB concentrations were significantly lower in non-anorexic patients with cancer than those of the control group (P = 0.028). In contrast, patients with cancer and anorexia had lower levels of anti-ClpB immunoglobulins (Ig)M (P < 0.0001) and of both α-MSH IgM and IgG (P < 0.05) with respect to controls. Moreover, in patients with cancer and anorexia, anti-ClpB IgG showed a trend of lower affinities compared with non-anorexic patients (P = 0.05).

Conclusions: Taken together, the results revealed a reduced humoral immune response to ClpB in patients with cancer and anorexia, which may lead to an enhanced satietogenic effect of this enterobacterial protein contributing to the mechanisms of reduced appetite.
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http://dx.doi.org/10.1016/j.nut.2020.110952DOI Listing
October 2020

Association Between Metabolic and Hormonal Derangements and Professional Exposure to Urban Pollution in a High Intensity Traffic Area.

Front Endocrinol (Lausanne) 2020 11;11:509. Epub 2020 Aug 11.

Institute of Translational Pharmacology, CNR, Rome, Italy.

Studies suggest a relation between exposure to air particulate matter (PM) pollution and greater cardiovascular morbidity, as well as increased risk for obesity and diabetes. We aimed to identify association(s) between nutritional and metabolic status and exposure to environmental pollution in a cohort of policemen exposed to high levels of air pollution. We considered adult municipal policemen, working in an urban area at high-traffic density with documented high levels of air PM (exposed group) compared to non-exposed policemen. Clinical characteristics, including the presence/absence of metabolic syndrome, were recorded, and serum biomarkers, including adiponectin, leptin, and ghrelin, were assessed. One hundred ninety-nine participants were enrolled, 100 in the exposed group and 99 in the non-exposed group. Metabolic syndrome was documented in 32% of exposed group and in 52.5% of non-exposed group ( = 0.008). In the exposed group, we found a positive correlation between body mass index and serum leptin as well as in the non-exposed group ( < 0.0001). Within the exposed group, subjects with metabolic syndrome showed lower serum adiponectin ( < 0.0001) and higher leptin ( = 0.002) levels with respect to those without metabolic syndrome, whereas in the non-exposed group, subjects with metabolic syndrome showed only higher leptin levels when compared to those without metabolic syndrome ( = 0.01). Among the participants with metabolic syndrome, we found lower adiponectin levels in those of the exposed group with respect to the non-exposed ones ( = 0.007). When comparing the exposed and non-exposed groups, after stratifying participants for Homeostatic Model Assessment for Insulin Resistance >2.5, we found lower adiponectin levels in those of the exposed group with respect to the non-exposed ones ( = 0.038). Exposure to air PM pollution was associated with lower levels of adiponectin in adult males with metabolic syndrome.
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http://dx.doi.org/10.3389/fendo.2020.00509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431614PMC
August 2020

Left Ventricular Mass Index as Potential Surrogate of Muscularity in Patients With Systemic Sclerosis Without Cardiovascular Disease.

JPEN J Parenter Enteral Nutr 2020 Aug 14. Epub 2020 Aug 14.

Department of Translational and Precision Medicine (formerly Department of Clinical Medicine), Sapienza University of Rome, Rome, Italy.

Background: Systemic sclerosis (SSc) may be associated with protein-energy malnutrition. It was demonstrated that left ventricular mass (LVM) reflected poor nutrition status in SSc patients, and no data are available on LVM as a surrogate measure of muscularity. We aimed to evaluate, in SSc patients, the relationship between muscle mass and LVM as a novel indicator of muscularity in this setting.

Methods: SSc patients and healthy controls (HCs) were considered and underwent echocardiography to assess LVM and LVM index (LVMI). Body composition, including fat-free mass index (FFMI), phase angle (PhA), and body cell mass index (BCMI), was analyzed by multifrequency bioelectrical impedance analysis.

Results: Sixty-four SSc patients (aged 51 ± 13 years) and 30 HCs (aged 46 ± 13 years) were enrolled. BCMI and PhA were lower in SSc patients compared with HCs (P < .001). LVM and LVMI were not different between SSc patients and HCs (P = .068, P = .14, respectively). In SSc patients, a significant correlation was shown between LVMI and FFMI (τ = 0.192, P = .026); in multiple regression analysis, FFMI was significantly associated with the Malnutrition Universal Screening Tool (P < .0001), LVMI (P = .01), and disease severity scale (P = .02).

Conclusion: Changes in body composition were present in SSc patients, particularly in terms of BMCI and PhA. A correlation between LVMI and FFMI as indexes of muscularity exists in this cohort, suggesting that cardiac mass might be used as a surrogate of nutrition status in this setting.
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http://dx.doi.org/10.1002/jpen.1999DOI Listing
August 2020

The Facts about Food after Cancer Diagnosis: A Systematic Review of Prospective Cohort Studies.

Nutrients 2020 Aug 5;12(8). Epub 2020 Aug 5.

Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy.

Nutritional guidelines suggest specific energy and protein requirements for patients with cancer. However, cancer patients, often malnourished, use self-made or web-based diets to ameliorate the prognosis of their disease. This review aimed to investigate the associations between post-diagnostic diet and prognostic outcomes in cancer patients. A systematic literature search was performed in Pubmed and Web of Science databases from inception to 30 October 2019, based on fixed inclusion and exclusion criteria. The risk of bias was assessed. A total of 29 prospective studies was identified. Breast ( = 11), colorectal ( = 9), prostate ( = 8) cancers are the most studied. Low- fat diet, healthy quality diet, regular consumption of fiber such as vegetables and high-quality protein intake are beneficial while Western diet (WD) and high consumption of saturated fats could be associated with a higher risk of mortality. Bladder ( = 1), gynecological ( = 1), lung, stomach, and pancreatic cancers still remain almost unexplored. This systematic review suggested that detrimental dietary patterns such as WD should be avoided but none of the food categories (meat, dairy products) should be eliminated in cancer patients' diet. Further large prospective studies are needed to assess the role of post-diagnostic diet in patients with cancer.
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http://dx.doi.org/10.3390/nu12082345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468771PMC
August 2020

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

Toxins (Basel) 2020 06 9;12(6). Epub 2020 Jun 9.

Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus ( ≤ 0.01) and serum uric acid ( ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, ≤ 0.01; base excess, ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin ( = 0.008) and fasting glucose levels ( = 0.022), HOMA-IR ( = 0.004), as well as lower total serum cholesterol ( = 0.012), triglycerides ( = 0.016), C-reactive protein ( = 0.044) and homocysteine ( = 0.044) and higher HDL ( < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.
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http://dx.doi.org/10.3390/toxins12060381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354587PMC
June 2020

Effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular risk indices in renal cell carcinoma.

Cancer Med 2020 06 9;9(11):3752-3757. Epub 2020 Apr 9.

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

Background: Sunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment.

Methods: Patients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow-mediated dilation (FMD), carotid intima media thickness (IMT), ankle-brachial pressure index (ABI), and 24-hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1.

Results: Twenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P < .001), HOMA-IR (P < .01), and serum total cholesterol levels (P = .01). Moreover at T1 we found a significant increase in systolic and diastolic blood pressure (P ≤ .001) and 24-hour proteinuria (P < .001) compared to baseline, whereas no changes in IMT and ABI were detected.

Conclusion: The changes observed overtime after sunitinib treatment in terms of markers of early endothelial dysfunction, blood pressure, as well as in glucose/insulin metabolism and proteinuria may contribute to increase CV risk in RCC patients and suggest a strict follow-up in this setting. Larger evidences are mandatory to confirm our observations.
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http://dx.doi.org/10.1002/cam4.2910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286450PMC
June 2020

Effect of Low-Protein Diet and Inulin on Microbiota and Clinical Parameters in Patients with Chronic Kidney Disease.

Nutrients 2019 Dec 9;11(12). Epub 2019 Dec 9.

Department of Biology, Tor Vergata University of Rome, 00133 Rome, Italy.

Introduction: The gut microbiota has coevolved with humans for a mutually beneficial coexistence and plays an important role in health and disease. A dysbiotic gut microbiome may contribute to progression to chronic kidney disease (CKD) and CKD-related complications such as cardiovascular disease. Microbiota modulation through the administration of prebiotics may represent an important therapeutic target.

Aim: We sought to evaluate the effects of a low-protein diet (LPD) (0.6 g/kg/day) with or without the intake of the prebiotic inulin (19 g/day) on microbiota and clinical parameters in CKD patients.

Materials And Methods: We performed a longitudinal, prospective, controlled, and interventional study on 16 patients: 9 patients treated with LPD (0.6 g/kg/day) and inulin (19 g/day) and 7 patients (control group) treated only with LPD (0.6 g/kg/day). Clinical evaluations were performed and fecal samples were collected for a subsequent evaluation of the intestinal microbiota in all patients. These tests were carried out before the initiation of LPD, with or without inulin, at baseline (T0) and at 6 months (T2). The microbiota of 16 healthy control (HC) subjects was also analyzed in order to identify potential dysbiosis between patients and healthy subjects.

Results: Gut microbiota of CKD patients was different from that of healthy controls. The LPD was able to significantly increase the frequencies of Akkermansiaceae and Bacteroidaceae and decrease the frequencies of Christensenellaceae, Clostridiaceae, Lactobacillaceae, and Pasteurellaceae. Only Bifidobacteriaceae were increased when the LPD was accompanied by oral inulin intake. We showed a significant reduction of serum uric acid (SUA) and C-reactive protein (CRP) in patients treated with LPD and inulin ( = 0.018 and = 0.003, respectively), an improvement in SF-36 (physical role functioning and general health perceptions; = 0.03 and = 0.01, respectively), and a significant increase of serum bicarbonate both in patients treated with LPD ( = 0.026) or with LPD and inulin ( = 0.01). Moreover, in patients treated with LPD and inulin, we observed a significant reduction in circulating tumor necrosis factor alpha (TNF-α) ( = 0.041) and plasma nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) ( = 0.027) levels. We did not find a significant difference in the circulating levels of Interleukin (IL)-1β ( = 0.529) and IL-6 ( = 0.828) in the two groups.

Conclusions: LPD, associated or not with inulin, modified gut microbiota and modulated inflammatory and metabolic parameters in patients with CKD. Our results suggest that interventions attempting to modulate the gut microbiome may represent novel strategies to improve clinical outcomes in CKD patients and may provide useful therapeutic effects.
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http://dx.doi.org/10.3390/nu11123006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950025PMC
December 2019

α-lipoic acid in patients with autosomal dominant polycystic kidney disease.

Nutrition 2020 03 27;71:110594. Epub 2019 Sep 27.

Department of Translational and Precision Medicine, Secondary Hypertension Unit, Sapienza University of Rome, Italy.

Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls.

Methods: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2).

Results: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1β, and tumor necrosis factor-α concentrations in either group.

Conclusions: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.
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http://dx.doi.org/10.1016/j.nut.2019.110594DOI Listing
March 2020

Metabolic Reprogramming Promotes Myogenesis During Aging.

Front Physiol 2019 10;10:897. Epub 2019 Jul 10.

Department of Orthopaedics and Traumatology, Hospital "Maggiore della Carità", Università del Piemonte Orientale (UPO), Novara, Italy.

Sarcopenia is the age-related progressive loss of skeletal muscle mass and strength finally leading to poor physical performance. Impaired myogenesis contributes to the pathogenesis of sarcopenia, while mitochondrial dysfunctions are thought to play a primary role in skeletal muscle loss during aging. Here we studied the link between myogenesis and metabolism. In particular, we analyzed the effect of the metabolic modulator trimetazidine (TMZ) on myogenesis in aging. We show that reprogramming the metabolism by TMZ treatment for 12 consecutive days stimulates myogenic gene expression in skeletal muscle of 22-month-old mice. Our data also reveal that TMZ increases the levels of mitochondrial proteins and stimulates the oxidative metabolism in aged muscles, this finding being in line with our previous observations in cachectic mice. Moreover, we show that, besides TMZ also other types of metabolic modulators (i.e., 5-Aminoimidazole-4-Carboxamide Ribofuranoside-AICAR) can stimulate differentiation of skeletal muscle progenitors . Overall, our results reveal that reprogramming the metabolism stimulates myogenesis while triggering mitochondrial proteins synthesis during aging. Together with the previously reported ability of TMZ to increase muscle strength in aged mice, these new data suggest an interesting non-invasive therapeutic strategy which could contribute to improving muscle quality and neuromuscular communication in the elderly, and counteracting sarcopenia.
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http://dx.doi.org/10.3389/fphys.2019.00897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636331PMC
July 2019

Investigational drugs for the treatment of cancer cachexia: a focus on phase I and phase II clinical trials.

Expert Opin Investig Drugs 2019 Aug 26;28(8):733-740. Epub 2019 Jul 26.

a Department of Translational and Precision Medicine, Sapienza University of Rome , Rome , Italy.

: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. : This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their phase-I and phase-II study design. The major outcomes were appetite stimulation, weight gain, improvement of muscle mass and function, modulation of inflammation, and quality of life. : The molecules discussed act on molecular pathways involved in cancer cachexia; they modulate appetite, anabolic effects, inflammation and direct interaction with muscle. Considering the multifactorial aspects of the cachexia syndrome, the combination of these drugs with metabolic and nutritional interventions may represent the most promising therapeutic approach to cancer cachexia.
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http://dx.doi.org/10.1080/13543784.2019.1646727DOI Listing
August 2019

Longitudinal Physical Activity Change During Hemodialysis and Its Association With Body Composition and Plasma BAIBA Levels.

Front Physiol 2019 25;10:805. Epub 2019 Jun 25.

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.

Low physical activity is frequent in end stage renal disease. We evaluated the longitudinal change in physical activity and its barriers in hemodialysis (HD) patients and the association between the patterns of physical activity change, body composition, and beta-aminoisobutyric acid (BAIBA), as circulating myokine. This is an observational study, where HD patients were considered in a 24-month follow-up. We assessed overtime the change of physical inactivity and its barriers by validated questionnaires, body composition by bioimpedance analysis, muscle strength by hand-dynamometer, and plasma BAIBA levels by liquid chromatography spectrometry. Parametric and non-parametric analyses were performed, as appropriate. Out of the 49 patients studied at baseline, 39 completed the first-year follow-up, and 29 completed the second year. At month 12, active patients had higher intracellular water (ICW) ( = 0.001) and cellular mass ( < 0.001), as well as at month 24 ( = 0.012, = 0.002; respectively) with respect to inactive. A significant reduction in ICW was shown at month 12 ( = 0.011) and month 24 ( = 0.014) in all patients. The barrier "reduced walking ability" was more frequent in inactive patients with respect to active at month 12 ( = 0.003) and at month 24 ( = 0.05). At month 24, plasma BAIBA levels were higher among active patients with respect to inactive ( = 0.043) and a correlation was seen between muscle strength and ICW ( = 0.51, = 0.005); normalizing BAIBA per body mass index, we found it lower with respect to baseline ( = 0.004), as well as after correcting per ICW ( = 0.001), as marker of muscle mass. A high prevalence of physical inactivity persisted during a 24-month follow-up in this cohort. We found an association between physical activity and a decline in marker of muscularity and reduced plasma BAIBA levels.
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http://dx.doi.org/10.3389/fphys.2019.00805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603089PMC
June 2019

Muscle derangement and alteration of the nutritional machinery in NSCLC.

Crit Rev Oncol Hematol 2019 Sep 15;141:43-53. Epub 2019 Jun 15.

Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy. Electronic address:

Weight loss and depletion of nutritional status are frequent presentation hallmarks in non-small cell lung cancer (NSCLC). Decline in muscle mass is a major component in weight loss and may have both a prognostic and predictive value for survival and treatment-related toxicities. Recent findings suggest that weight and skeletal muscle mass gain during treatment may represent surrogate markers for outcome in advanced NSCLC patients. Herein we present an in-depth view of the impact of nutritional status derangements on NSCLC patients' outcome, focusing on lean body mass variations during disease course. We explored the impact of malnutrition with a major attention on novel treatment options. We reviewed molecular, metabolic and immunological mechanisms underlying muscle-wasting condition, which may exhibit a meaningful targeting potential. Incorporating a specialized and accurate body composition assessment into a comprehensive, patient-centered and tailored intervention will facilitate the achievement of nutritional goals and optimal care for lung cancer patients.
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http://dx.doi.org/10.1016/j.critrevonc.2019.06.007DOI Listing
September 2019

The NUTRIREA-2 study.

Lancet 2019 04;393(10180):1502-1503

Department of Translational and Precision Medicine, Sapienza University of Rome, Rome 00185, Italy.

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http://dx.doi.org/10.1016/S0140-6736(18)33199-4DOI Listing
April 2019

Nutritional and metabolic derangements in Mediterranean cancer patients and survivors: the ECPC 2016 survey.

J Cachexia Sarcopenia Muscle 2019 06 5;10(3):517-525. Epub 2019 Apr 5.

European Cancer Patient Coalition (ECPC), Brussels, Belgium.

Background: The prevalence of nutritional derangements in patients with cancer is high. This survey assessed patients' awareness of cancer-related nutritional issues and evaluated how important they perceive the impact of nutrition on cancer and treatment to be.

Methods: A structured questionnaire was developed to determine: presence of feeding problems, perception of nutrition importance, and perception of physicians' approach to nutrition. The European Cancer Patient Coalition disseminated the questionnaire to its members in 10 countries. The Mediterranean cluster (Italy, Spain, and Greece) was analysed separately to further determine specific patterns in answers.

Results: In total, 907 respondents completed the questionnaire (68.8% female participants; 51.7% with cancer; 48.3% cancer survivors; 59.3% diagnosed with cancer ≤3 years ago; 46.2% receiving treatment for <1 year). Feeding problems during illness/therapy were experienced by 72.5% (628/867) of all respondents (Italian: 90.0%, 117/130), although up to 53.9% (467/867) reported that physicians did not check their feeding status. Overall, 69.6% (586/842) of respondents reported weight loss after cancer diagnosis (moderate to severe: 36.7%, 309/842). For Italian respondents, the percentages of overall weight loss and moderate-to-severe weight loss were 85.1% (109/128) and 70.3% (90/128), respectively. Only 35.0% (295/842) of all respondents reported having their weight measured regularly during treatment; 45.7% (385/842) believed their physician considered cancer-related weight loss unimportant. Respondents [all: 56.9% (472/830); Italian: 73.0% (92/126); Spanish: 68.9% (42/61); Greek: 79.7% (47/59)] were unaware of supplements' negative effects during therapy or the need to inform their physician about these supplements [all: 43.6% (362/830); Italian: 55.6% (70/126); Spanish: 47.5% (29/61); Greek: 49.2% (29/59)]. The term 'cachexia' was generally unknown to respondents [all: 72.9% (603/827); Italian: 64.3% (81/126); Spanish: 68.9% (42/61); Greek: 47.5% (28/59)] and most respondents [all: 92.4% (764/827); Italian: 91.3% (115/126); Spanish: 91.8% (56/61); Greek: 86.4% (51/59)] received no cachexia-related information.

Conclusions: Patients reported differences in perspective between them and physicians on cancer-related nutritional issues and the specific nutritional approaches available for cancer treatment. Increasing physician focus on nutrition during treatment, particularly among Italian physicians, and providing information on optimizing nutrition to patients are essential factors to improving patients' quality of life.
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http://dx.doi.org/10.1002/jcsm.12420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596398PMC
June 2019

DHA Oral Supplementation Modulates Serum Epoxydocosapentaenoic Acid (EDP) Levels in Breast Cancer Patients.

Oxid Med Cell Longev 2019 5;2019:1280987. Epub 2019 Mar 5.

Department of Translational and Precision Medicine, Sapienza University of Rome, v.le dell'Università 37, 00185 Rome, Italy.

Introduction: The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. Epoxydocosapentaenoic acids (EDPs), metabolites of the DHA, are hypothesized to be responsible for some beneficial effects. In the present study, we aimed to assess the circulating 19,20-EDP levels in breast cancer (BC) patients and in healthy controls before and after DHA oral supplementation and the potential differences in the DHA conversion in 19,20-EDPs between patients with different BC presentations.

Methods: BC patients and healthy controls were supplemented with DHA (algal oil) for 10 days (2 g/day). Blood samples were collected at baseline (T0) and after supplementation (T1) to assess EDP (19,20-EDP) serum levels by liquid chromatography spectrometry.

Results: 33 BC patients and 10 controls were studied. EDP values at T0 were not different between patients and controls. At T1, we found an increase in 19,20-EDP levels in BC patients ( < 0.00001) and in controls ( < 0.001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation ( = 0.03). According to immunohistochemical subtype, luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A ( = 0.02).

Conclusions: DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population.
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http://dx.doi.org/10.1155/2019/1280987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425377PMC
July 2019

Sarcopenia and cardiovascular risk indices in patients with chronic kidney disease on conservative and replacement therapy.

Nutrition 2019 06 11;62:108-114. Epub 2018 Dec 11.

Department of Translational and Precision Medicine, Sapienza University of Rome, Italy.

Objective: Chronic kidney disease (CKD) is a condition with high cardiovascular mortality associated with emerging risk factors, including sarcopenia. Several mechanisms can affect muscle mass, such as vitamin D deficiency, low protein intake, physical inactivity, metabolic acidosis, and inflammation leading to a worsening of cardiovascular outcomes and cognitive function. We aimed to evaluate the prevalence of sarcopenia in CKD patients on conservative and replacement therapy and the associations between sarcopenia and markers of atherosclerosis, endothelial dysfunction, psychological and cognitive function.

Methods: We enrolled CKD patients (stage 3/5 KDIGO [Kidney Disease: Improving Global Outcomes]) and hemodialysis, peritoneal dialysis, and post-kidney transplant patients. Clinical, laboratory and instrumental assessments, including bioimpedance analysis, hand-grip strength, intima media thickness, flow-mediated dilation, and epicardial adipose tissue, were performed in addition to analysis of psychological and cognitive status by the Montreal Cognitive Assessment, Mini-Mental State Examination, and Geriatric Depression Scale.

Results: A total of 77 patients (43 male) with a mean age of 69.6 ± 9.85 y were studied. According to validated criteria (using bioimpedance analysis and hand-grip strength), the prevalence of sarcopenia was 49.4%. Sarcopenic patients had higher values of intima media thickness (P = 0.032) and epicardial adipose tissue (P = 0.012) and lower flow-mediated dilation (P = 0.002), total cholesterol (P = 0.005), and high-density lipoprotein cholesterol (P = 0.008) with respect to non-sarcopenic patients. We found higher Geriatric Depression Scale scores (P = 0.04) in sarcopenic patients, whereas we did not find differences between the two groups in Mini-Mental State Examination and Montreal Cognitive Assessment score.

Conclusion: Sarcopenia is highly prevalent in CKD/end stage renal disease patients and is associated with changes in early systemic indices of atherosclerosis and endothelial dysfunction, known as markers of worse prognosis.
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http://dx.doi.org/10.1016/j.nut.2018.12.005DOI Listing
June 2019

Nutrition support for treating cancer-associated weight loss: an update.

Curr Opin Support Palliat Care 2018 12;12(4):434-438

Department of Clinical Medicine, Sapienza University of Rome, Italy.

Purpose Of Review: Patients with cancer present high risk for involuntary body weight loss and reduced food intake, which, contributing to progressive tissue wasting and affecting the nutritional status, are often under-estimated in the clinical practice. In this article, we aimed at focusing on cancer-associated weight loss and investigating recent evidences on the indications of nutritional interventions to treat this condition.

Recent Findings: During the last few years, increased emphasis has been addressed on the mechanisms underlying body weight loss in cancer that can be induced by either cancer metabolism and inflammation, either several side-effects of the anticancer treatments. This led to consider clinical parameters, such as BMI, body weight change and food intake, and their modification overtime, in predicting patient's overall survival. In this light, nutritional support has to be considered to maintain or restore nutritional status, improve tolerance to oncological therapies, and ameliorate physical performance and quality of life.

Summary: Increased awareness on weight loss in cancer patients and on cancer cachexia is needed to carry out a nutritional assessment at an early stage of cancer journey and to establish its management and nutritional support to obtain advantages in terms of treatment tolerance and clinical outcomes.
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http://dx.doi.org/10.1097/SPC.0000000000000383DOI Listing
December 2018

Peritoneal dialysis in older adults: Evaluation of clinical, nutritional, metabolic outcomes, and quality of life.

Medicine (Baltimore) 2018 Aug;97(35):e11953

Department of Clinical Medicine, Sapienza University of Rome Department of Nephrology, Catholic University of Sacred Heart Department of Obstetrical-GynecologicalSciences and Urologic Sciences Department of Dynamic and Clinic Psychology, Sapienza University of Rome Department of Anaesthesia and Intensive care,Catholic University of Sacred Heart, Rome, Italy.

The number of older adults requiring dialysis is increasing worldwide, whereas the use of peritoneal dialysis (PD) in this population is lower with respect to younger patients, despite the theoretical advantages of PD respect to hemodialysis. This is most likely due to the concern that older patients may not be able to correctly and safely manage PD.We aimed to prospectively compare clinical, nutritional and metabolic outcomes and measures of quality of life between younger (<65 years old) and older (≥65 years old) patients on PD.PD patients were enrolled and divided into 2 groups according to age (Group A < 65 years, Group B ≥ 65 years). Clinical and instrumental parameters, and quality of life were evaluated at baseline (start of PD) (T0) and at 24 months (T1). Technique survival, mortality, total number of hospitalizations, and the index of peritonitis (episodes of peritonitis/month) were also evaluated.Fifty-one patients starting PD were enrolled. Group A included 22 patients (48.7 ± 8.3 years), and Group B consisted of 29 patients (74.1 ± 6.4 years). At baseline, the 2 groups showed no differences in cognitive status, whereas Group A showed higher total cholesterol (P = .03), LDL (P = .03), and triglycerides (P = .03) levels and lower body mass index (P = .02) and carotid intima media thickness (P < .0001) with respect to Group B. At T1 Group B showed, compared to baseline, a significant reduction in albumin (P < .0001) and phosphorus (P = .045) levels, while no significant differences on body composition, technique survival, total number of hospitalizations, index of peritonitis, and quality of life indices were observed.Our data do not show clinically relevant barriers to use PD in older adult patients, supporting its use in this population. Nutritional and metabolic parameters should be carefully monitored in older PD patients.
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http://dx.doi.org/10.1097/MD.0000000000011953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6393061PMC
August 2018

Neurological and Psychological Changes in Hemodialysis Patients Before and After the Treatment.

Ther Apher Dial 2018 Oct 22;22(5):530-538. Epub 2018 Jun 22.

Department of Dynamic and Clinic Psychology, Sapienza University of Rome, Rome, Italy.

Neurological, psychological, and cognitive disorders in chronic kidney disease may contribute to poor quality of life in these patients. The aim of this study was to assess the electroencephalographic, psychological, and cognitive changes before and after hemodialysis (HD) compared with healthy controls (HC). Sixteen HD patients and 15 HC were enrolled. Electroencephalogram (EEG), Minnesota multiphasic personality inventory (MMPI-2) Satisfaction profile (SAT-P), and Neuropsychological test Global z-scores (NPZ5) were performed before (T0) and after (T1) HD treatment and in HC. Renal function, inflammatory markers and mineral metabolism indexes were also evaluated. Patients did not show significant differences before and after HD in the absolute and relative power of band of EEG, except in Theta/Alpha index (P < 0.001). At T1, HD patients showed significant differences in Beta, Delta and Theta band, in addition to Theta/alpha index, with respect to HC. Moreover, HD patients showed significant differences in specific MMPI-2 clinical and content scales, SAT-P domains and NPZ5 tests of memory and concentration with respect to HC. We also observed significant correlations between renal function, mineral metabolism, inflammatory markers and psychocognitive alterations. In our sample EEG abnormalities tend to reduce, but not significantly, after HD treatment and differences remain present with respect to HC. In HD patients cognitive and psychological alterations were associated with reduced quality of life and correlated with mineral metabolism and inflammation. Modification in EEG and in psychological and cognitive parameters should be assessed in a larger HD population to confirm our observation.
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http://dx.doi.org/10.1111/1744-9987.12672DOI Listing
October 2018

The Challenges of Nutritional Assessment in Cirrhosis.

Curr Nutr Rep 2017 Sep 18;6(3):274-280. Epub 2017 Jul 18.

Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, California.

Purpose Of Review: Nutritional status in patients with cirrhosis is very frequently associated with macro- and micronutrient deficiencies. Cirrhosis itself is the cause of malnutrition and nutritional deficiencies but these conditions have to be identified and addressed properly as they can worsen the prognosis of cirrhosis. The goals of this review are to 1) identify and describe the challenges associated with nutritional assessment in cirrhosis and 2) describe recent advancements when using clinical, laboratory, and instrumental tools in the evaluation of malnourished patients with liver diseases.

Recent Findings: The most promising tools for nutritional assessment in cirrhosis include the evaluation of body composition with phase angle obtained by bioelectrical impedance analysis, computed tomography transverse images at the level of third lumbar vertebra. The Royal-Free Hospital global assessment algorithm appears to be helpful but needs further validation.

Summary: Nutritional assessment in cirrhosis is challenging as several factors, including edema, can interfere with it and because of lack of a validated gold standard. Regardless, nutritional assessment methods have been developed in recent years and should gain relevance in the clinical practice.
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http://dx.doi.org/10.1007/s13668-017-0216-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703218PMC
September 2017

PTEN expression and its association with glucose control and calorie supplementation in critically ill patients.

Clin Nutr 2018 12 4;37(6 Pt A):2186-2190. Epub 2017 Nov 4.

Department of Clinical Medicine, Sapienza University of Rome, Italy. Electronic address:

Background & Aim: Phosphatase and tensin homologue (PTEN) reduces insulin sensitivity. Since critically ill patients present insulin resistance, we aimed at assessing the role of PTEN expression on glucose homeostasis and clinical outcome in patients admitted to an intensive care unit (ICU) and receiving artificial nutrition.

Methods: Observational, single-center study conducted in one ICU in Rome, Italy on adult patients hospitalized for trauma. Plasma glucose levels and its variability were recorded in patients receiving artificial nutrition. PTEN expression was measured by western blotting analysis and the associations between PTEN, plasma glucose levels and variability, and calories administered were investigated. Parametric and non-parametric tests were used, as appropriate.

Results: Twenty consecutive patients (13 men and 7 women, mean age of 37.3 ± 12.7 years) were studied. No correlation between plasma glucose and PTEN was documented (r = -0.15, P = 0.55), neither between glycemic variability and PTEN expression (r = -0.00, P = 0.99). However, total kcal/day administered and PTEN expression significantly correlated (r = 0.56, P = 0.01). Also, patients with PTEN levels below the median received less kcal/day than those with PTEN above the median (P = 0.048). This association was more pronounced when normalized per body weight (P = 0.03) and after adjusting for the average of insulin daily administered (P = 0.02).

Conclusions: PTEN expression might significantly contribute to glucose homeostasis and disposal in critically ill patients receiving artificial nutrition. Larger samples are necessary to confirm our observation.

Clinical Trial Registry Number: NCT01796847 (www.clinicaltrials.gov) submitted on February 11, 2013.
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http://dx.doi.org/10.1016/j.clnu.2017.10.021DOI Listing
December 2018

Association between change in serum bicarbonate and change in thyroid hormone levels in patients receiving conventional or more frequent maintenance haemodialysis.

Nephrology (Carlton) 2019 Jan;24(1):81-87

Division of Nephrology, Department of Internal Medicine, University of California, Davis, California, USA.

Aim: Correction of metabolic acidosis in patients with chronic kidney disease has been associated with improvement in thyroid function. We examined whether changes in bicarbonate were associated with changes in thyroid function in patients with end-stage renal disease receiving conventional or more frequent haemodialysis.

Methods: In the Frequent Hemodialysis Network Trials, the relationship between changes in serum bicarbonate, free triiodothyronine (FT3) and free thyroxine (FT4) was examined among 147 and 48 patients with endogenous thyroid function who received conventional (3×/week) or more frequent (6×/week) haemodialysis (Daily Trial) or who received conventional or more frequent nocturnal haemodialysis (Nocturnal Trial). Equilibrated normalized protein catabolic rate (enPCR) was examined to account for nutritional factors affecting both acid load and thyroid function.

Results: Increasing dialysis frequency was associated with increased bicarbonate level. Baseline bicarbonate level was not associated with baseline FT3 and FT4. Change in bicarbonate level was not associated with changes in FT3 and FT4 in the Daily Trial nor for FT4 in the Nocturnal Trial (r ≤ 0.14, P > 0.21). While, a significant correlation between change in serum bicarbonate and change in FT3 (r = 0.44, P = 0.02) was observed in the Nocturnal Trial; findings were no longer significant after adjusting for change in enPCR (r = 0.37, P = 0.08). For participants with baseline bicarbonate <23 mmol/L, no association between change in bicarbonate and change in thyroid indices were seen in the Daily Trial; for the Nocturnal Trial, findings were also not significant for change in FT3 and the association between change in bicarbonate and change in FT4 (r = 0.54, P = 0.03) was no longer significant after adjusting for enPCR (r = 0.45, P = 0.11).

Conclusion: Changes in bicarbonate were not associated with changes in thyroid hormone levels after adjusting for enPCR, as a marker of nutritional status. Future studies should examine whether improvement in acid base status improves thyroid function in haemodialysis patients with evidence of thyroid hypofunction.
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http://dx.doi.org/10.1111/nep.13187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916580PMC
January 2019

Anti-catabolic neurohormonal blockade to improve skeletal muscle during disease.

Expert Opin Biol Ther 2017 12 23;17(12):1583. Epub 2017 Oct 23.

a Department of Clinical Medicine , Sapienza - University of Rome , Rome , Italy.

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http://dx.doi.org/10.1080/14712598.2017.1392029DOI Listing
December 2017