Publications by authors named "Filippo Rossi Fanelli"

111 Publications

The metabolite beta-aminoisobutyric acid and physical inactivity among hemodialysis patients.

Nutrition 2017 Feb 30;34:101-107. Epub 2016 Jul 30.

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

Objective: Physical inactivity is frequent in patients on hemodialysis (HD), and represents a reliable predictor of morbidity and mortality. Beta-aminoisobutyric acid (BAIBA) is a contraction-induced myokine, the plasma levels of which increase with exercise and are inversely associated with metabolic risk factors. The aim of this study was to ascertain whether physical inactivity and clinical parameters relate to plasma BAIBA levels in this patient population.

Methods: Adult patients on HD were included, and the presence of physical inactivity was assessed. BAIBA levels were measured in these patients and in healthy individuals. We assessed barriers to physical activity, including 23 items regarding psychophysical and financial barriers. Body composition was assessed by bioimpedance and muscle strength by handgrip dynamometer. Nonparametric tests and logistic regression analyses were performed.

Results: Forty-nine patients on HD were studied; 49% were physically active and 51% were inactive. Of the patients, 43 reported barriers to physical activity and 61% of inactive patients reported three or more barriers. BAIBA levels were lower in patients on HD with respect to controls (P < 0.001). Stratifying HD patients as active and inactive, both groups showed significantly lower BAIBA levels versus controls (P = 0.0005, P < 0.001, respectively). Nondiabetic patients on HD showed increased BAIBA levels compared with diabetic patients (P < 0.001). Patients on HD endorsing the two most frequent barriers showed lower BAIBA levels than those not reporting these barriers (P = 0.006). Active patients showed higher intracellular water (%) (P = 0.008), and active and inactive patients showed significant correlation between total body muscle mass and handgrip strength (P = 0.04, P = 0.005, respectively).

Conclusions: Physical inactivity is highly prevalent among patients on HD and BAIBA correlates with barriers to physical activity reported by inactive patients.
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http://dx.doi.org/10.1016/j.nut.2016.07.012DOI Listing
February 2017

Cancer anorexia: hypothalamic activity and its association with inflammation and appetite-regulating peptides in lung cancer.

J Cachexia Sarcopenia Muscle 2017 Feb 5;8(1):40-47. Epub 2016 Oct 5.

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

Background: Energy homeostasis is mediated by the hypothalamus, whose inflammation-induced functional derangements contribute to the onset of anorexia in cancer. By using functional magnetic resonance imaging (fMRI), we determined the patterns of hypothalamic activation after oral intake in anorexic (A), non-anorexic (NA) cancer patients, and in controls (C).

Methods: Lung cancer patients were considered. Hypothalamic activation was recorded in A and NA patients and in C by fMRI, before (T0), immediately after (T1) the administration of an oral nutritional supplement, and after 15 min (T2). The grey of the hypothalamus and Blood Oxygen Level Dependent (BOLD) intensity were calculated and normalized for basal conditions. Interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, ghrelin, and leptin plasma levels were measured. A statistical parametric mapping was used.

Results: Thirteen lung cancer patients (7 M, 6 F; 9A, 4NA) and 2 C (1 M, 1 F) were enrolled. Controls had the lowest BOLD intensity. At all-time points, anorexic patients showed lower hypothalamic activity compared with NA (P < 0.001) (T0: 585.57 ± 55.69 vs. 667.92 ± 33.18, respectively; T1: 536.50 ± 61.70 vs. 624.49 ± 55.51, respectively; T2: 556.44 ± 58.51 vs. 615.43 ± 71.50, respectively). Anorexic patients showed greater BOLD signal reduction during T0-T1 than NA (-8.5% vs. -6.80%, P < 0.001). Independently from the presence of anorexia, BOLD signals modification before and after oral challenge correlated with basal values of IL-1 and ghrelin (P < 0.001).

Conclusions: Hypothalamic activity in A cancer patients is reduced respect to NA and responds differently to oral challenges. This suggests a central control of appetite dysregulation during cancer anorexia, before, and after oral intake.
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http://dx.doi.org/10.1002/jcsm.12156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326827PMC
February 2017

Nutritional status is a predictor of outcome in cancer patients, irrespective of stage.

Intern Emerg Med 2017 Feb 17;12(1):135-136. Epub 2016 Sep 17.

Department of Clinical Medicine, Sapienza University, viale dell'Università 37, 00185, Rome, Italy.

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http://dx.doi.org/10.1007/s11739-016-1539-yDOI Listing
February 2017

Mini-Nutritional Assessment, Malnutrition Universal Screening Tool, and Nutrition Risk Screening Tool for the Nutritional Evaluation of Older Nursing Home Residents.

J Am Med Dir Assoc 2016 10 12;17(10):959.e11-8. Epub 2016 Aug 12.

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

Introduction: Malnutrition plays a major role in clinical and functional impairment in older adults. The use of validated, user-friendly and rapid screening tools for malnutrition in the elderly may improve the diagnosis and, possibly, the prognosis. The aim of this study was to assess the agreement between Mini-Nutritional Assessment (MNA), considered as a reference tool, MNA short form (MNA-SF), Malnutrition Universal Screening Tool (MUST), and Nutrition Risk Screening (NRS-2002) in elderly institutionalized participants.

Methods: Participants were enrolled among nursing home residents and underwent a multidimensional evaluation. Predictive value and survival analysis were performed to compare the nutritional classifications obtained from the different tools.

Results: A total of 246 participants (164 women, age: 82.3 ± 9 years, and 82 men, age: 76.5 ± 11 years) were enrolled. Based on MNA, 22.6% of females and 17% of males were classified as malnourished; 56.7% of women and 61% of men were at risk of malnutrition. Agreement between MNA and MUST or NRS-2002 was classified as "fair" (k = 0.270 and 0.291, respectively; P < .001), whereas the agreement between MNA and MNA-SF was classified as "moderate" (k = 0.588; P < .001). Because of the high percentage of false negative participants, MUST and NRS-2002 presented a low overall predictive value compared with MNA and MNA-SF. Clinical parameters were significantly different in false negative participants with MUST or NRS-2002 from true negative and true positive individuals using the reference tool. For all screening tools, there was a significant association between malnutrition and mortality. MNA showed the best predictive value for survival among well-nourished participants.

Conclusions: Functional, psychological, and cognitive parameters, not considered in MUST and NRS-2002 tools, are probably more important risk factors for malnutrition than acute illness in geriatric long-term care inpatient settings and may account for the low predictive value of these tests. MNA-SF seems to combine the predictive capacity of the full version of the MNA with a sufficiently short time of administration.
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http://dx.doi.org/10.1016/j.jamda.2016.06.028DOI Listing
October 2016

Autophagy is induced in the skeletal muscle of cachectic cancer patients.

Sci Rep 2016 07 27;6:30340. Epub 2016 Jul 27.

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

Basal rates of autophagy can be markedly accelerated by environmental stresses. Recently, autophagy has been involved in cancer-induced muscle wasting. Aim of this study has been to evaluate if autophagy is induced in the skeletal muscle of cancer patients. The expression (mRNA and protein) of autophagic markers has been evaluated in intraoperative muscle biopsies. Beclin-1 protein levels were increased in cachectic cancer patients, suggesting autophagy induction. LC3B-I protein levels were not significantly modified. LC3B-II protein levels were significantly increased in cachectic cancer patients suggesting either increased autophagosome formation or reduced autophagosome turnover. Conversely, p62 protein levels were increased in cachectic and non-cachectic cancer patients, suggesting impaired autophagosome clearance. As for mitophagy, both Bnip3 and Nix/Bnip3L show a trend to increase in cachectic patients. In the same patients, Parkin levels significantly increased, while PINK1 was unchanged. At gene level, Beclin-1, p-62, BNIP3, NIX/BNIP3L and TFEB mRNAs were not significantly modulated, while LC3B and PINK1 mRNA levels were increased and decreased, respectively, in cachectic cancer patients. Autophagy is induced in the skeletal muscle of cachectic cancer patients, although autophagosome clearance appears to be impaired. Further studies should evaluate whether modulation of autophagy could represent a relevant therapeutic strategy in cancer cachexia.
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http://dx.doi.org/10.1038/srep30340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962093PMC
July 2016

Novel therapeutic options for cachexia and sarcopenia.

Expert Opin Biol Ther 2016 10 11;16(10):1239-44. Epub 2016 Jul 11.

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

Introduction: Cachexia and sarcopenia are conditions phenotypically characterized by muscle loss and represent a factor of poor prognosis, increasing patients' morbidity and mortality. Cachectic and sarcopenic patients often suffer from low quality of life, presenting lower muscle strength and appetite loss, which makes research on novel treatment strategies to ameliorate clinical response including patient's symptoms, the objective of scientific interest.

Areas Covered: This article covers recent developments in the area of cachexia and sarcopenia treatment and therapeutic interventions, targeting central nervous system involvement, key inflammatory and muscle-specific metabolic pathways.

Expert Opinion: A number of promising agents have being evaluated, such as enobosarm, a selected androgen receptor modulator, and anamorelin, a ghrelin agonist which have been recently studied in phase III trials. These and other agents (i.e., infliximab, tocilizumab, MABp1, bimagrumab) have shown significant impact on reversal of skeletal muscle loss, but limited effect on physical function. In the last few years advancement in the number and type of potential treatments for cachexia and sarcopenia have been obtained and we have now available more data on measurable effects of several drugs on patients' nutritional and metabolic parameters and outcomes.
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http://dx.doi.org/10.1080/14712598.2016.1208168DOI Listing
October 2016

Effect of the specific proteasome inhibitor bortezomib on cancer-related muscle wasting.

J Cachexia Sarcopenia Muscle 2016 06 7;7(3):345-54. Epub 2015 Jul 7.

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

Background: Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)-ubiquitin-proteasome-dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF-κB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study has been to investigate whether pharmacological inhibition of proteasome by bortezomib may prevent skeletal muscle wasting in experimental cancer cachexia.

Methods: Cancer cachexia was induced in rats by intraperitoneal injection of Yoshida AH-130 ascites hepatoma cells and in mice by subcutaneous inoculation of C26 carcinoma cells. Animals were then further randomized to receive bortezomib. The AH-130 hosts were weighted and sacrificed under anaesthesia, on Days 3, 4, 5, and 7 after tumour inoculation, while C26-bearing mice were weighted and sacrificed under anaesthesia 12 days after tumour transplantation. NF-κB and proteasome activation, MuRF1 and atrogin-1 mRNA expression and beclin-1 protein levels were evaluated in the gastrocnemius of controls and AH-130 hosts.

Results: Bortezomib administration in the AH-130 hosts, although able to reduce proteasome and NF-κB DNA-binding activity in the skeletal muscle on Day 7 after tumour transplantation, did not prevent body weight loss and muscle wasting. In addition, bortezomib exerted a transient toxicity, as evidenced by the reduced food intake and by the increase in NF-κB DNA-binding activity in the AH-130 hosts 3 days after tumour transplantation. Beclin-1 protein levels were increased by bortezomib treatment in Day 3 controls but were unchanged on both Days 3 and 7 in the AH-130 hosts, suggesting that an early compensatory induction of autophagy may exist in healthy but not in tumour-bearing animals. Regarding C26-bearing mice, bortezomib did not prevent as well body and muscle weight loss 12 days after tumour implantation.

Conclusions: The results obtained suggest that proteasome inhibition by bortezomib is not able to prevent muscle wasting in experimental cancer cachexia. Further studies are needed to address the issue whether a different dosage of bortezomib alone or in combination with other drugs modulating different molecular pathways may effectively prevent muscle wasting during cancer cachexia.
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http://dx.doi.org/10.1002/jcsm.12050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864285PMC
June 2016

The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer.

Int J Mol Sci 2016 Apr 5;17(4):505. Epub 2016 Apr 5.

Department of Clinical Medicine, Sapienza University of Rome, viale dell'Università 37, 00185 Rome, Italy.

Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.
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http://dx.doi.org/10.3390/ijms17040505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4848961PMC
April 2016

Validating Appetite Assessment Tools Among Patients Receiving Hemodialysis.

J Ren Nutr 2016 Mar 28;26(2):103-10. Epub 2015 Oct 28.

Division of Nephrology, University of California, San Francisco, San Francisco, California; Nephrology Section, San Francisco Veterans Affairs Medical Center, San Francisco, California.

Objective: To test the performance of appetite assessment tools among patients receiving hemodialysis (HD).

Design: Cross-sectional.

Subjects: Two hundred twenty-one patients receiving HD enrolled in seven dialysis facilities in Northern California.

Intervention: We assessed 5 appetite assessment tools (self-assessment of appetite, subjective assessment of appetite, visual analog scale [VAS], Functional Assessment of Anorexia/Cachexia Therapy [FAACT] score, and the Anorexia Questionnaire [AQ]).

Main Outcome Measures: Reported food intake, normalized protein catabolic rate, and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake.

Results: Fifty-eight (26%) patients reported food intake ≤ 50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All the tools were significantly associated with food intake ≤ 50% (P < .001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake ≤ 50% (C-statistic 0.80 and 0.76). Patients with food intake ≤ 50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; P = .03). Normalized protein catabolic rate was lower among anorexic patients based on the VAS (1.1 ± 0.3 vs 1.2 ± 0.3, P = .03). Ln interleukin-6 correlated inversely with food intake (P = .03), but neither interleukin-6 nor C-reactive protein correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (P = .02), prealbumin (P = .02) and adiponectin concentrations (P = .03).

Conclusions: Alternative appetite assessment tools yielded widely different estimates of the prevalence of anorexia in HD. When considering self-reported food intake as the criterion standard for anorexia, the FAACT score and VAS discriminated patients reasonably well.
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http://dx.doi.org/10.1053/j.jrn.2015.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796001PMC
March 2016

Contribution of Neuroinflammation to the Pathogenesis of Cancer Cachexia.

Mediators Inflamm 2015 4;2015:801685. Epub 2015 Oct 4.

Department of Clinical Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.

Inflammation characterizes the course of acute and chronic diseases and is largely responsible for the metabolic and behavioral changes occurring during the clinical journey of patients. Robust data indicate that, during cancer, functional modifications within brain areas regulating energy homeostasis contribute to the onset of anorexia, reduced food intake, and increased catabolism of muscle mass and adipose tissue. In particular, functional changes are associated with increased hypothalamic concentration of proinflammatory cytokines, which suggests that neuroinflammation may represent the adaptive response of the brain to peripheral challenges, including tumor growth. Within this conceptual framework, the vagus nerve appears to be involved in conveying alert signals to the hypothalamus, whereas hypothalamic serotonin appears to contribute to triggering catabolic signals.
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http://dx.doi.org/10.1155/2015/801685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609516PMC
August 2016

Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease.

Intern Emerg Med 2016 Mar 22;11(2):213-7. Epub 2015 Oct 22.

Clinical Immunology Unit, Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy.

Interstitial lung disease (ILD) is a hallmark of systemic sclerosis (SSc). Although high-resolution computed tomography (HRCT) is the gold standard to diagnose ILD, recently lung ultrasound (LUS) has emerged in SSc patients as a new promising technique for the ILD evaluation, noninvasive and radiation-free. The aim of this study was to evaluate if there is a correlation between LUS, chest HRCT, pulmonary function tests findings and clinical variables of the disease. Thirty-nine patients (33 women and 6 men; mean age 51 ± 15.2 years) underwent clinical examination, HRCT, pulmonary function tests and LUS for detection of B-lines. A positive correlation exists between the number of B-lines and the HRCT score (r = 0.81, p < 0.0001), conversely a negative correlation exists between the number of B-lines and diffusing capacity of the lung for carbon monoxide (DLCO) (r = -0.63, p < 0.0001). The number of B-lines increases along with the progression of the capillaroscopic damage. A statistically significant difference in the number of B-lines was found between patients with and without digital ulcers [42 (3-84) vs 16 (4-55)]. We found that the number of B-lines increased with the progression of both HRCT score and digital vascular damage. LUS may therefore, be a useful tool to determine the best timing for HRCT execution, thus, preventing for many patients a continuous and useless exposure to ionizing radiation.
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http://dx.doi.org/10.1007/s11739-015-1329-yDOI Listing
March 2016

Carnitine for the treatment of cachexia: Lights and shadows.

Int J Cardiol 2015 Nov 2;198:180-1. Epub 2015 Jul 2.

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

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http://dx.doi.org/10.1016/j.ijcard.2015.06.156DOI Listing
November 2015

Cardiac, Inflammatory and Metabolic Parameters: Hemodialysis versus Peritoneal Dialysis.

Cardiorenal Med 2015 Feb 13;5(1):20-30. Epub 2014 Dec 13.

Department of Clinical Medicine, Hemodialysis Unit, Umberto I, Polyclinic of Rome, Sapienza University of Rome, Rome, Italy.

Introduction: Mortality in dialysis patients is higher than in the general population, and cardiovascular disease represents the leading cause of death. Hypertension and volume overload are important risk factors for the development of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal dialysis (PD) patients. Other factors are mainly represented by hyperparathyroidism, vascular calcification, arterial stiffness and inflammation. The aim of this study was to compare blood pressure (BP) and metabolic parameters with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch calcification (AAC) and LV mass index (LVMI)] between PD and HD patients.

Materials And Methods: 45 patients (23 HD and 22 PD patients) were enrolled. BP measurements, echocardiography and chest X-ray were performed in each patient to determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated.

Results: LVMI was higher in PD than HD patients (139 ŷ 19 vs. 104 ŷ 22; p = 0.04). In PD patients, a significant correlation between iPTH, C-reactive protein and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03, respectively). The CTR was increased in PD patients as compared to HD patients, while no significant differences in cardiac calcifications were determined.

Conclusions: Our data indicate that HD patients present more effective BP control than PD patients. Adequate fluid and metabolic control are necessary to assess the adequacy of BP, which is strongly correlated with the increase in LVMI and with the increased CTR in dialysis patients. PD is a home therapy and allows a better quality of life, but PD patients may present a further increased cardiovascular risk if not adequately monitored.
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http://dx.doi.org/10.1159/000369588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327338PMC
February 2015

Anorexia assessment in patients with cancer: a crucial issue to improve the outcome.

J Clin Oncol 2015 May 9;33(13):1513. Epub 2015 Mar 9.

Sapienza University of Rome, Rome, Italy.

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http://dx.doi.org/10.1200/JCO.2014.59.9548DOI Listing
May 2015

The involvement of T regulatory lymphocytes in a cohort of lupus nephritis patients: a pilot study.

Intern Emerg Med 2015 Sep 27;10(6):677-83. Epub 2015 Feb 27.

Clinical Medicine and Rheumatology, Integrated Research Center, Campus Bio-Medico University, Rome, Italy.

T regulator lymphocytes (Tregs) play a key role in the maintenance of immune tolerance and in the development of autoimmune diseases. Expression of Foxp3 is specific for Tregs, and can be used for the identification of these cells. This study investigated the variations of Tregs Foxp3+ in the kidney biopsies inflammatory infiltrate of different lupus nephritis classes compared to that of ANCA glomerulonephritis, acute tubulointerstitial nephritis and nephroangiosclerosis. Sections of paraffin-embedded tissue have been stained by immunohistochemistry with anti-CD3 and anti-FoxP3 antibodies. We find that the ratio of FoxP3+/CD3+ cells is significantly lower in patients with lupus nephritis class IV and in patients with vasculitides than in the course of nephroangiosclerosis, tubulointerstitial nephritis and lupus nephritis class V. The data presented herein demonstrate a decrease of FoxP3+ Treg cells in the inflammatory infiltrate of lupus nephritis, particularly during the most active phases of lupus nephritis, as observed in the course of a IV class nephritis.
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http://dx.doi.org/10.1007/s11739-015-1212-xDOI Listing
September 2015

Cachexia: a preventable comorbidity of cancer. A T.A.R.G.E.T. approach.

Crit Rev Oncol Hematol 2015 May 7;94(2):251-9. Epub 2014 Nov 7.

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

Although relevant achievements in the treatment of cancer have been obtained, some barriers still remain in the prevention and treatments of cancer comorbidities, including cachexia. Indeed, the enormous advances in the understanding of the pathogenesis of cancer cachexia have not been paralleled by effective strategies aimed at modifying the cultural approach to this devastating condition. Too little attention is still paid to the nutritional and metabolic changes occurring in cancer, despite their negative effects on patients' tolerance to antineoplastic treatments and outcome. We propose a T.A.R.G.E.T. approach as a novel strategy, encompassing active interventions and research development within the different domains influencing the onset and the progression of cancer cachexia. Moreover, based on the most recent clinical evidences, we suggest that cachexia should be considered a comorbidity of cancer.
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http://dx.doi.org/10.1016/j.critrevonc.2014.10.014DOI Listing
May 2015

The role for dietary omega-3 fatty acids supplementation in older adults.

Nutrients 2014 Oct 3;6(10):4058-73. Epub 2014 Oct 3.

Department of Clinical Medicine Sapienza, University of Rome, Viale dell'Università 37, 00185 Rome, Italy.

Optimal nutrition is one of the most important determinants of healthier ageing, reducing the risk of disability, maintaining mental and physical functions, and thus preserving and ensuring a better quality of life. Dietary intake and nutrient absorption decline with age, thus increasing the risk of malnutrition, morbidity and mortality. Specific nutrients, particularly long-chain omega-3 polyunsaturated fatty acids (PUFAs), might have the potential of preventing and reducing co-morbidities in older adults. Omega-3 PUFAs are able to modulate inflammation, hyperlipidemia, platelet aggregation, and hypertension. Different mechanisms contribute to these effects, including conditioning cell membrane function and composition, eicosanoid production, and gene expression. The present review analyzes the influence of omega-3 PUFAs status and intake on brain function, cardiovascular system, immune function, muscle performance and bone health in older adults. Omega-3 FAs may have substantial benefits in reducing the risk of cognitive decline in older people. The available data encourage higher intakes of omega-3 PUFAs in the diet or via specific supplements. More studies are needed to confirm the role of omega-3 FAs in maintaining bone health and preventing the loss of muscle mass and function associated with ageing. In summary, omega-3 PUFAs are now identified as potential key nutrients, safe and effective in the treatment and prevention of several negative consequences of ageing.
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http://dx.doi.org/10.3390/nu6104058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210907PMC
October 2014

Prevalence and clinical features of patients with the cardiorenal syndrome admitted to an internal medicine ward.

Cardiorenal Med 2014 Aug 6;4(2):88-94. Epub 2014 May 6.

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

Background: Many patients admitted to a Department of Internal Medicine have different degrees of heart and kidney dysfunction. Mortality, morbidity and cost of care greatly increase when cardiac and renal diseases coexist.

Methods: A retrospective cohort study was conducted on 1,087 patients admitted from December 2009 to December 2012 to evaluate the prevalence of the cardiorenal syndrome (CRS) and clinical features.

Results: Out of 1,087 patients discharged from our unit during the study period, 190 (17.5%) were diagnosed as having CRS and classified into five types. CRS was more common in males (68.9%). CRS type 1 was associated with higher age (79.9 ± 8.9 years) and accounted for 61.5% of all deaths (p < 0.001), representing a risk factor for mortality (OR 4.23, 95% CI 1.8-10). Congestive heart failure was significantly different among the five CRS types (p < 0.0001) with a greater frequency in type 1 patients. Infectious diseases were more frequent in CRS types 1, 3 and 5 (p < 0.05). Pneumonia presented a statistically higher frequency in CRS types 1 and 5 compared to other classes (p < 0.01), and community-acquired infections were statistically more frequent in CRS types 1 and 5 (p < 0.05). The distribution of community-acquired pneumonia was different among the classes (p < 0.01) with a higher frequency in CRS types 1, 3 and 5.

Conclusion: CRS is a condition that is more frequently observed in the clinical practice. The identification of predisposing trigger factors, such as infectious diseases, particularly in the elderly, plays a key role in reducing morbidity and mortality. An early recognition can be useful to optimize therapy, encourage a multidisciplinary approach and prevent complications.
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http://dx.doi.org/10.1159/000362566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164062PMC
August 2014

A Case of Pneumocystis jirovecii Pneumonia in a Severely Malnourished, HIV-Negative Patient: A Role for Malnutrition in Opportunistic Infections?

JPEN J Parenter Enteral Nutr 2016 07 29;40(5):722-4. Epub 2014 Aug 29.

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

Malnutrition increases the risk of infections in patients receiving medical and surgical procedures, but it is not clear whether it may facilitate also the development of opportunistic infections in human immunodeficiency virus (HIV)-negative patients not receiving immunosuppressive therapies. Here we report the first case of a non-HIV, severely malnourished woman who developed Pneumocystis jirovecii pneumonia. This report highlights the clinical relevance of malnutrition as a determinant of immune suppression, which in turn may also favor opportunistic infections. Therefore, routine nutrition screening and assessment, as well as timely start of nutrition therapy, should be prioritized in daily clinical practice to reduce complications and improve outcome.
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http://dx.doi.org/10.1177/0148607114548072DOI Listing
July 2016

Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin.

World J Gastrointest Pharmacol Ther 2014 Aug;5(3):196-9

Antonietta Gigante, Gianluca Di Lazzaro Giraldi, Maria Ludovica Gasperini, Biagio Barbano, Marta Liberatori, Liborio Sardo, Francesca Di Mario, Antonella Giorgi, Filippo Rossi-Fanelli, Antonio Amoroso, Department of Clinical Medicine, "Sapienza" University of Rome, 00185 Rome, Italy.

The administration of statins in patients with liver disease is not an absolute contraindication. Hepatotoxicity is a rare and often dose-related event and in the literature there are only a few described cases of fatal rhabdomyolysis in patients with chronic liver disease after statin administration. During treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, the factors responsible for myopathy may either be related to the patient, or due to interactions with other medications that are metabolic substrates of the same isozymes and therefore able to increase blood statin concentration. The most important side effects consist of increased transaminase levels, abdominal pain or muscle weakness, increased serum levels of creatine kinase and rhabdomyolysis. In this article we report a case of fatal rhabdomyolysis with acute renal failure after gastric endoscopy, where midazolam was used as a sedation agent in a patient with chronic liver disease treated with a high dose of atorvastatin. Therefore, we suggest paying particular attention to the potential risks of associating atorvastatin and midazolam in patients with chronic liver disease who need to undergo gastric endoscopy.
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http://dx.doi.org/10.4292/wjgpt.v5.i3.196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133446PMC
August 2014

Cancer cachexia: towards integrated therapeutic interventions.

Expert Opin Biol Ther 2014 Oct 12;14(10):1379-81. Epub 2014 Jul 12.

Sapienza University of Rome, Department of Clinical Medicine , Viale dell'Università, 37, 00185 Roma , Italy +39 06 499 72016 ;

Biological treatments represent a novel approach to counteract cancer cachexia. Monoclonal antibodies targeting cytokines and molecules responsible for muscle wasting, with an anti-inflammatory effect, however, still have several limitations and need further clinical investigation. New research in this field will contribute to the better understanding of the multifactorial pathogenesis of cancer cachexia, while favoring the consolidation of multimodal preventive and therapeutic strategies encompassing nutritional and pharmacological treatments. New pharmacological therapies and conventional nutritional treatments will soon integrate in the 'parallel pathway', aimed at early recognition, prevention and treatment of the metabolic and nutritional derangements occurring in cancer. This will likely produce improvement in quality of life, tolerance to treatments and survival.
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http://dx.doi.org/10.1517/14712598.2014.939068DOI Listing
October 2014

Towards improved awareness and earlier diagnosis of early onset colorectal neoplasms.

Intern Emerg Med 2014 Sep 2;9(6):615-6. Epub 2014 Jul 2.

Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185, Rome, Italy.

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http://dx.doi.org/10.1007/s11739-014-1101-8DOI Listing
September 2014

Ghrelin: from discovery to cancer cachexia therapy.

Curr Opin Clin Nutr Metab Care 2014 Sep;17(5):471-6

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

Purpose Of Review: Despite the high prevalence of cancer cachexia, a condition that negatively impacts patients' prognosis and quality of life, effective therapies are still lacking. Ghrelin is a peptide hormone involved in anabolic and homeostatic functions, whose mechanisms of action are still only partially clarified, but with promising positive effects in cancer cachexia. Recently, the therapeutic administration of ghrelin in cancer has been shown to counteract loss of body mass and function, including muscle, and we specifically focus on this novel evidence.

Recent Findings: Recent research aimed at developing new pharmacological therapies to prevent muscle wasting has used ghrelin and molecules acting as synthetic ghrelin receptor agonists with different modalities of administration and with high selectivity for specific targeted tissues. Positive effects of these therapies were described in cancer cachexia and chemotherapy-induced muscle wasting. New insights into the mechanisms of action of ghrelin revealed how its pleiotropic effects should be ascribed both to systemic anti-inflammation effect and to muscle-specific action through the activation of the antiatrophic molecular cascade.

Summary: Growing interest arises from the identification of ghrelin as a valid and well tolerated therapeutic option to counteract structural and functional wasting derived from tumour growth.
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http://dx.doi.org/10.1097/MCO.0000000000000075DOI Listing
September 2014

Nutritional status measured by BMI is impaired and correlates with left ventricular mass in patients with systemic sclerosis.

Nutrition 2014 Feb;30(2):204-9

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

Objective: Systemic sclerosis (SSc) is a multisystemic chronic disease that is complicated by protein-energy malnutrition (PEM). Considering that PEM also may influence left ventricular mass (LVM), the aim of this study was to evaluate whether LVM is related to patients' nutritional status and to determine clinically relevant features of SSc.

Methods: Adult patients referring to our institution were considered. Body weight, height, body mass index (BMI), involuntary weight loss, and the presence of gastrointestinal symptoms were recorded. Echocardiography was performed to assess LVM, using the Devereux regression formula. Results were then normalized by body surface area. Pattern, skin thickening, disease activity and severity, and duration were assessed to characterize SSc.

Results: Ninety-four patents with SSc (81 women and 13 men; median duration of disease 7 y) were studied. The prevalence of PEM as assessed by BMI < 20 kg/m(2) was 19%, whereas 15% of patients reported involuntary weight loss of any degree. Patients who lost weight reported gastrointestinal symptoms more frequently (P < 0.05). PEM was not associated with disease activity. LVM (g/m(2)) correlated with patients' BMI (r = 0.32; P < 0.01), and the vascular domain of disease severity (DDS; r = 0.21; P < 0.05), but it showed a negative correlation with skin thickening (r = -0.21 P = 0.01). Patients with ulcers had a significantly greater LVM than patients without skin lesions.

Conclusions: Our study shows that LVM correlates with patients' BMI, skin thickening, and the vascular domain of DSS. Therefore, LVM could serve as a marker of nutritional status and fibrosis in patients with SSc.
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http://dx.doi.org/10.1016/j.nut.2013.07.025DOI Listing
February 2014

Sarcopenia and chemotherapy dosing in obese patients.

Nat Rev Clin Oncol 2013 Nov 8;10(11):664. Epub 2013 Oct 8.

Department of Clinical Medicine, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.

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http://dx.doi.org/10.1038/nrclinonc.2013.108-c1DOI Listing
November 2013

Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials.

Amino Acids 2013 Dec 22;45(6):1273-92. Epub 2013 Sep 22.

Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università, 37, 00185, Rome, Italy.

Beta-hydroxy-beta-methylbutyrate (HMB), a metabolite of the branched-chain amino acid leucine, is extensively used by athletes and bodybuilders in order to increase strength, muscle mass and exercise performance. We performed a systematic review of the clinical literature on the effectiveness of HMB supplementation in healthy and pathological conditions (i.e. training programs, aging, acute and chronic diseases, and after bariatric surgery). We reviewed all clinical trials indexed in Medline that tested HMB supplementation as well as all the experimental data regarding HMB intracellular mechanisms of action. Search terms included: randomized controlled trials, controlled clinical trials, single- and double-blind method, HMB, proteolytic pathways, muscle atrophy, cachexia, and training. We found out 13 studies testing HMB in healthy young trained subjects, 11 in healthy young untrained subjects, 9 in patients affected by chronic diseases (i.e. cancer, HIV, chronic obstructive pulmonary disease), and 6 in elderly subjects. The indexed studies support that HMB is effective in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases. Most of the selected studies showed the effectiveness of HMB in preventing exercise-related muscle damage in healthy trained and untrained individuals as well as muscle loss during chronic diseases. The usual dose of 3 g/day may be routinely recommended to maintain or improve muscle mass and function in health and disease. The safety profile of HMB is unequivocal. Further, well-designed clinical studies are needed to confirm effectiveness and mode of action of HMB, particularly in pathological conditions.
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http://dx.doi.org/10.1007/s00726-013-1592-zDOI Listing
December 2013

Early changes of muscle insulin-like growth factor-1 and myostatin gene expression in gastric cancer patients.

Muscle Nerve 2013 Sep 17;48(3):387-92. Epub 2013 Jul 17.

Department of Experimental Medicine and Oncology, University of Turin, Turin, Italy.

Introduction: Cachexia increases morbidity and mortality of cancer patients. The progressive loss of muscle mass negatively affects physical function and quality of life. We previously showed reduced muscle insulin-like growth factor-1 (IGF-1) expression and enhanced myostatin signaling in tumor-bearing animals. This study was aimed at investigating whether similar perturbations occur in gastric cancer patients.

Methods: Early perturbations of myostatin and IGF-1 signaling (including the expression of muscle-specific ubiquitin ligases) were investigated in 16 gastric cancer patients and in 6 controls by analyzing muscle mRNA expression with semiquantitative reverse transcriptase polymerase chain reaction (PCR) and real-time PCR.

Results: In gastric cancer patients, muscle mRNA levels for IGF-1, myostatin, and atrogin-1 were reduced irrespective of weight loss (≤5% or >5%), whereas MuRF1 expression was unchanged.

Conclusions: IGF-1 and myostatin mRNA levels are downregulated in gastric cancer patients who have minimal or no weight loss. These early alterations are particularly relevant in order to devise preventive and therapeutic strategies for cancer cachexia.
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http://dx.doi.org/10.1002/mus.23798DOI Listing
September 2013

Muscle depletion and the prediction of chemotherapy toxicity.

Intern Emerg Med 2013 Aug 11;8(5):373-5. Epub 2013 Jun 11.

Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, Rome, Italy.

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http://dx.doi.org/10.1007/s11739-013-0966-2DOI Listing
August 2013

MuRF-1 and p-GSK3β expression in muscle atrophy of cirrhosis.

Liver Int 2013 May 24;33(5):714-21. Epub 2013 Feb 24.

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

Background: Chronic diseases, including cirrhosis, are often accompanied by protein-energy malnutrition and muscle loss, which in turn negatively affect quality of life, morbidity and mortality. Unlike other chronic conditions, few data are available on the molecular mechanisms underlying muscle wasting in this clinical setting.

Aims: To assess mechanisms of muscle atrophy in patients with cirrhosis.

Methods: Nutritional [subjective global assessment (SGA) and anthropometry] and metabolic assessment was performed in 30 cirrhotic patients awaiting liver transplantation. Rectus abdominis biopsies were obtained intraoperatively in 22 cirrhotic patients and in 10 well-nourished subjects undergoing elective surgery for non-neoplastic disease, as a control group. Total RNA was extracted and mRNA for atrogenes (MuRF-1, Atrogin-1/MAFbx), myostatin (MSTN), GSK3β and IGF-1 was assayed.

Results: A total of 50% of cirrhotic patients were malnourished based on SGA, while 53% were muscle-depleted according to mid-arm muscle area (MAMA<5th percentile). MuRF-1 RNA expression was significantly increased in malnourished cirrhotic patients (SGA-B/C) vs. well-nourished patients (SGA-A) (P = 0.01). The phosphorylation of GSK3β was up-regulated in cirrhotic patients with hepatocellular carcinoma (HCC) vs. patients without tumour (P < 0.05).

Conclusions: Muscle loss is frequently found in end-stage liver disease patients. Molecular factors pertaining to signalling pathways known to be involved in the regulation of muscle mass are altered during cirrhosis and HCC.
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http://dx.doi.org/10.1111/liv.12128DOI Listing
May 2013

Timing of antioxidant supplementation is critical in improving anorexia in an experimental model of cancer.

Int J Food Sci Nutr 2013 Aug 9;64(5):570-4. Epub 2013 Jan 9.

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

Increased oxidative stress may contribute to cancer anorexia, which could be ameliorated by antioxidant supplementation. methylcholanthrene (MCA) sarcoma-bearing Fisher rats were studied. After tumour inoculation, rats were randomly assigned to standard diet (CTR group, n = 6), or to an antioxidant-enriched diet (AOX group, n = 8). Eight more rats (STD-AOX group) switched from standard to antioxidant diet when anorexia developed. At the end of the study, food intake (FI, g/d), body weight and tumour weight (g) were recorded, and plasma samples were obtained. On day 16, anorexia has appeared only in CTR and STD-AOX animals. At the end of the study, FI in AOX animals was still higher than in the other groups (p = 0.08). No differences in body and tumour weights were observed among groups. However, hydrogen peroxide and interleukin-1β levels were significantly reduced only in AOX rats. Data obtained suggest that early antioxidant supplementation improves cancer anorexia, ameliorates oxidative stress and reduces inflammation.
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http://dx.doi.org/10.3109/09637486.2012.759189DOI Listing
August 2013