Association between serum levels of GDF-15, suPAR, PIVKA-II, sdLDL and clinical outcomes in hospitalized COVID-19 patients.

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

Tryptophan metabolism and kynurenine metabolites in cancer: systemic nutritional and metabolic implications.

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

Bioimpedance-assessed muscle wasting and its relation to nutritional intake during the first week of ICU: a pre-planned secondary analysis of Nutriti Study.

BACKGROUND: Muscle mass evaluation in ICU is crucial since its loss is related with long term complications, including physical impairment. However, quantifying muscle wasting with available bedside tools (ultrasound and bioimpedance analysis) must be more primarily understood. Bioimpedance analysis (BIA) provides estimates of muscle mass and phase angle (PA). The primary aim of this study was to evaluate muscle mass changes with bioimpedance analysis during the first 7 days after ICU admission. Secondary aims searched for correlations between muscular loss and caloric and protein debt. METHODS: Patients with an expected ICU-stay ≥ 72 h and the need for artificial nutritional support were evaluated for study inclusion. BIA evaluation of muscle mass and phase angle were performed at ICU admission and after 7 days. Considering the difference between ideal caloric and protein targets, with adequate nutritional macronutrients delivered, we calculated the caloric and protein debt. We analyzed the potential correlation between caloric and protein debt and changes in muscle mass and phase angle. RESULTS: 72 patients from September 1st to October 30th, 2019 and from August 1st to October 30th, 2021 were included in the final statistical analysis. Median age was 68 [59-77] years, mainly men (72%) admitted due to respiratory failure (25%), and requiring invasive mechanical ventilation for 7 [4-10] days. Median ICU stay was 8 [6-12] days. Bioimpedance data at ICU admission and after 7 days showed that MM and PA resulted significantly reduced after 7 days of critically illness, 34.3 kg vs 30.6 kg (p < 0.0001) and 4.90° vs 4.35° (p = 0.0004) respectively. Mean muscle loss was 3.84 ± 6.7 kg, accounting for 8.4% [1-14] MM reduction. Correlation between caloric debt (r = 0.14, p = 0.13) and protein debt (r = 0.18, p = 0.13) with change in MM was absent. Similarly, no correlation was found between caloric debt (r = -0.057, p = 0.631) and protein debt (r = -0.095, p = 0.424) with changes in PA. CONCLUSIONS: bioimpedance analysis demonstrated that muscle mass and phase angle were significantly lower after 7 days in ICU. The total amount of calories and proteins does not correlate with changes in muscle mass and phase angle.

Assessment of lipolysis biomarkers in adipose tissue of patients with gastrointestinal cancer.

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

Muscularity and adiposity are differently associated with inflammatory and nutritional biomarkers among patients on hemodialysis and peritoneal dialysis.

PURPOSE: Nutritional alterations are prevalent in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD). We aimed at evaluating whether body composition parameters in HD vs PD are differently associated with nutritional and inflammatory biomarkers. METHODS: Body composition was assessed by bioimpedance analysis. Neutrophil to lymphocyte ratio (NLR), serum albumin and C-reactive protein were used as nutritional and inflammatory biomarkers. Multivariable linear regression analysis was used to determine association(s) of body composition parameters with biomarkers. RESULTS: We enrolled a total of 108 patients, 58 on HD and 50 on PD. Fat free mass percent was higher in HD patients than PD (p = 0.006) and higher extracellular water (ECW)/intracellular water (ICW) in HD compared to PD patients (p = 0.023), as well as fat mass index was greater in PD than HD (p = 0.004). In HD patients, albumin positively correlated with fat free mass (r = 0.42; p = 0.001) and ICW/h2 (r = 0.31; p = 0.02). In PD, NLR positively correlated with fat mass (r = 0.36; p = 0.01), fat mass index (r = 0.37; p = 0.01) and ECW (r = 0.41; p = 0.005), and negatively correlated with fat free mass percent (r = -0.30; p = 0.04) and ICW percent (r = -0.34; p = 0.02). By linear regression analysis, in HD fat free mass index was associated with albumin and the absence of diabetes. In PD, the association of fat free mass index was present with NLR. Regarding adiposity, in HD we found no association of ECW/ICW with NLR and CRP, whereas in PD the ECW/ICW was associated with NLR. CONCLUSION: Inflammation drives body composition changes with differences according to the type of dialysis, as expressed by the modulation of some circulating biomarkers.

Evaluation of Anorexia in Cancer and Its Association with Autonomic Nervous System Activity Assessed by Heart Rate Variability.

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

CHA2DS2-VASc score as a predictor of clinical outcomes in hospitalized patients with and without chronic kidney disease.

BACKGROUND: High CHA2DS2-VASc score (Congestive heart failure, Hypertension, Age > 75 years, Diabetes mellitus, prior Stroke or transient ischemic attack or thromboembolism, Vascular disease, Age 65-74 and Sex category) was associated with adverse clinical outcomes in different settings. The aim of the present study was to evaluate the association between CHA2DS2-VASc score and R2CHA2DS2-VASc score (which includes renal impairment) with in-hospital mortality and length of hospital stay in patients hospitalized in an internal medicine ward. METHODS: We enrolled 983 consecutive patients admitted during 3 years in an internal medicine ward. R2CHA2DS2-VASc score was calculated by adding 2 points to CHA2DS2-VASc for the presence of chronic kidney disease (CKD), defined according to K-DOQI. The primary outcome was a composite of all-cause mortality and length of hospital stay > 10 days. RESULTS: Patients with CKD stages 3-5 presented with increased CHA2DS2-VASc vs stages 1-2 (p < 0.001). The composite outcome occurred in 47.3% of inpatients. Multivariable linear logistic regression analyses adjusted for presence of infectious diseases and cancer, with the occurrence of composite outcome showed an adjusted OR of 1.349 (95% CI 1.248-1.462) and 1.254 (95% CI 1.179-1.336) for CHA2DS2-VASc and R2CHA2DS2-VASc scores, respectively. No differences were found in the association between CHA2DS2-VASc and R2CHA2DS2-VASc scores with the composite outcome (AUC 0.631 vs 0.630), and furthermore, adding the presence/absence of infectious diseases during hospitalization and positive cancer history to the models increased the AUC (0.667 and 0.663). CONCLUSIONS: Incrementally higher CHA2DS2-VASc score is associated with increased length of hospital stay and mortality in patients hospitalized in an internal medicine ward, regardless of the presence of CKD.

Small non-coding RNA profiling in patients with gastrointestinal cancer.

BACKGROUND: Small non-coding (snc)RNAs, including microRNAs and P-element induced wimpy testis (PIWI)-interacting-RNAs (piRNAs), crucially regulate gene expression in both physiological and pathological conditions. In particular, some muscle-specific microRNAs (myomiRs) have been involved in the pathogenesis of cancer-induced muscle wasting. The aims of the present study were (i) to profile sncRNAs in both skeletal muscle and plasma of gastrointestinal cancer patients and (ii) to investigate the association among differentially expressed sncRNAs and the level of muscularity at body composition analysis. METHODS: Surgical patients with gastrointestinal cancer or benign disease were recruited. Blood samples and muscle biopsies (rectus abdominis) were collected during surgery. Low muscularity patients were those at the lowest tertile of skeletal muscle index (SMI; CT-scan), whereas moderate/high muscularity patients were in the middle and highest SMI tertiles. SncRNAs in the muscle were assessed by RNAseq, circulating microRNAs were evaluated by qPCR. RESULTS: Cancer patients (n = 25; 13 females, 52%) showed a mean age of 71.6 ± 11.2 years, a median body weight loss of 4.2% and a mean BMI of 27.0 ± 3.2 kg/m2 . Control group (n = 15; 9 females, 60%) showed a mean age 58.1 ± 13.9 years and a mean BMI of 28.0 ± 4.3 kg/m2 . In cancer patients, the median L3-SMI (cm2 /m2 ) was 42.52 (34.42; 49.07). Males showed a median L3-SMI of 46.08 (41.17-51.79) and females a median L3-SMI of 40.77 (33.73-42.87). Moderate-high and low muscularity groups included 17 and 8 patients, respectively. As for circulating microRNAs, miR-21-5p and miR-133a-3p were up-regulated in patients compared with controls, whereas miR-15b-5p resulted down-regulated in the same comparison (about 30% of control values). Sample clustering by muscularity and sex revealed increased miR-133a-3p and miR-206 only in moderate-high muscularity males. SncRNA profiling in the muscle identified 373 microRNAs and 190 piRNAs (72.5% and 18.7% of raw reads, respectively). As for microRNAs, 10 were up-regulated, and 56 were down-regulated in cancer patients versus controls. Among the 24 dysregulated piRNAs, the majority were down-regulated, including the top two most expressed piRNAs in the muscle (piR-12790 and piR-2106). Network analysis on validated mRNA targets of down-regulated microRNAs revealed miR-15b-5p, miR-106a-5p and miR-106b-5p as main interactors of genes related to ubiquitin ligase/transferase activities. CONCLUSIONS: These results show dysregulation of both muscle microRNAs and piRNAs in cancer patients compared with controls, the former following a sex-specific pattern. Changes in circulating microRNAs are associated with the degree of muscularity rather than body weight loss.

Diarrhoea and constipation during artificial nutrition in intensive care unit: A prospective observational study.

PURPOSE: To describe the occurrence of gastrointestinal (GI) complications, specifically diarrhoea and constipation, in artificially (enterally or parenterally) fed critically ill patients within their first seven-day stay in Intensive Care Unit (ICU). METHODS: Observational prospective study conducted from September 1st to October 30th, 2019 and from August 1st to October 30th, 2021, in an ICU of a 1000-bed third-level hospital. General characteristics, nutritional variables, and medications administered were recorded and analysed. This study was registered on ClinicalTrials.gov (Identifier: NCT05473546). RESULTS: In total, 100 critically ill patients were included. Diarrhoea was present in 44 patients (44.0%), while constipation occurred in 22 (22.0%) patients. Patients with diarrhoea were generally those admitted for respiratory failure, whereas patients without diarrhoea were mostly affected by neurological disorders (22.7% vs 25%, respectively; p = 0.002). Likewise, patients with constipation were primarily those admitted for trauma (36.4%). Trauma patients were almost 24 times more likely to be constipated than patients with respiratory failure (OR 23.99, CI 1.38-418.0) and patients receiving diuretics were over 16 times more likely to have diarrhoea than patients not receiving diuretics (OR 16.25, IC 1.89-139.86). CONCLUSION: GI complications of enteral nutrition represent still a very common issue in ICU. The main predictor of constipation was an admission for trauma whereas the main predictor of diarrhoea was the use of diuretics. Clinicians should consider and integrate these findings into more personalized nutritional and management protocols to avoid gastrointestinal complications.

Disease-related malnutrition with inflammation and cachexia.

In 2010, the definition of cachexia was jointly developed by the European Society for Clinical Nutrition and Metabolism (ESPEN) Special Interest Groups (SIG) "Cachexia-anorexia in chronic wasting diseases" and "Nutrition in geriatrics". Cachexia was considered as a synonym of disease-related malnutrition (DRM) with inflammation by the ESPEN guidelines on definitions and terminology of clinical nutrition. Starting from these concepts and taking into account the available evidence the SIG "Cachexia-anorexia in chronic wasting diseases" conducted several meetings throughout 2020-2022 to discuss the similarities and differences between cachexia and DRM, the role of inflammation in DRM, and how it can be assessed. Moreover, in line with the Global Leadership Initiative on Malnutrition (GLIM) framework, in the future the SIG proposes to develop a prediction score to quantify the individual and combined effect(s) of multiple muscle and fat catabolic mechanisms, reduced food intake or assimilation and inflammation, which variably contribute to the cachectic/malnourished phenotype. This DRM/cachexia risk prediction score could consider the factors related to the direct mechanisms of muscle catabolism separately from those related to the reduction of nutrient intake and assimilation. Novel perspectives in the field of DRM with inflammation and cachexia were identified and described in the report.

Metabolic and histomorphological changes of adipose tissue in cachexia.

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

Pharmacological and nutritional therapy of children and adults with chronic intestinal pseudo-obstruction.

INTRODUCTION: Chronic intestinal pseudoobstruction (CIPO) is a rare, heterogenous, and severe form of gastrointestinal dysmotility. AREAS COVERED: Pertinent literature on pediatric and adult CIPO management has been assessed via PubMed, Scopus, and EMBASE from inception to June 2022. Prokinetics, aimed at restoring intestinal propulsion (e.g. orthopramides and substituted benzamides, acetyl cholinesterase inhibitors, serotonergic agents, and others), have been poorly tested and the available data showed only partial efficacy. Moreover, some prokinetic agents (e.g. orthopramides and substituted benzamides) can cause major side effects. CIPO-related small intestinal bacterial overgrowth requires treatment preferably via poorly absorbable antibiotics to avoid bacterial resistance. Apart from opioids, which worsen gut motility, analgesics should be considered to manage visceral pain, which might dominate the clinical manifestations. Nutritional support, via modified oral feeding, enteral, or parenteral nutrition, is key to halting CIPO-related malnutrition. EXPERT OPINION: There have been significant roadblocks preventing the development of CIPO treatment. Nonetheless, the considerable advancement in neurogastroenterology and pharmacological agents cast hopes to test the actual efficacy of new prokinetics via well-designed clinical trials. Adequate dietary strategies and supplementation remain of crucial importance. Taken together, novel pharmacological and nutritional options are expected to provide adequate treatments forthese patients.

Fatigue in Patients on Chronic Hemodialysis: The Role of Indoleamine 2,3-Dioxygenase (IDO) Activity, Interleukin-6, and Muscularity.

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer. 50 HD patients were enrolled, and fatigue was present in 24% of the cohort. Patients with fatigue showed higher Kyn/Trp (p = 0.005), were older (p = 0.007), and IL-6 levels resulted higher than in non-fatigue patients (p < 0.001). HD patients with fatigue showed lower intracellular water (surrogate of muscle mass) (p < 0.001), as well as lower hand grip strength (p = 0.02). The Kyn/Trp ratio positively correlated with IL-6 and ECW/ICW (p = 0.004 and p = 0.014). By logistic regression analysis, higher ICW/h2 was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity.

Prevention and treatment of catheter-related venous thrombosis in long-term parenteral nutrition: A SINuC position statement.

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

Effects of oral immunonutrition on histological changes of inflammatory infiltration of the tumor microenvironment among patients with a new diagnosis of gastric cancer.

OBJECTIVES: We assessed the effects of oral immunonutrition (OI) on the inflammatory infiltration of the tumor microenvironment (TME) of patients undergoing surgery for gastric cancer. METHODS: We analyzed patients at the time of their first gastric cancer diagnosis. We collected surgical tissue specimens (stomach), and performed an immunohistochemical analysis to evaluate the inflammatory infiltration of the TME. Patients receiving OI were compared with patients receiving standard oral nutritional supplements and no nutritional support. RESULTS: We enrolled 12 patients with gastric cancer in the study. The median body weight loss was 5.6%. Four patients received OI, five patients received standard nutritional supplement, and three patients received no nutritional supplementation. No difference in age, body mass index (BMI), and body weight loss was observed between the three groups. The OI group showed a tendency of increased number of T-lymphocyte cluster of differentiation (CD) 8+ compared with the other groups, as well as the number of CD83+ and CD68+. The absence of F4/80+ cells was documented only in the TME of the OI group, where a linear positive correlation was present between lymphocytes CD4+ and CD8+ (R = 0.48), and between CD4+ and CD83+ (R = 0.89), although not statistically significant. In the OI group, we observed a positive correlation (not significant) between the number of lymphocytes CD8+ and macrophages CD68+ (R = 0.70; P = 0.30). A strong significant correlation was documented between CD68+ and CD40+ (R = 0.99; P = 0.01), but this correlation did not reach the significance among the patients of the other two groups (R = 0.60; P = 0.116). CONCLUSIONS: The administration of OI in patients with gastric cancer might determine changes in inflammatory patterns of the TME.

Changes of gene expression in peripheral blood mononuclear cells of lung cancer patients with or without anorexia.

BACKGROUND & AIMS: Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia. METHODS: Genome-wide transcriptomic profiling was assessed in PBMCs RNA from newly diagnosed lung cancer patients and in a control group. RT-qPCR was used for selected genes. RESULTS: RNA-Seq analysis revealed among groups a large number of differentially expressed genes mainly implicated in immune system regulation, oxidative stress and cytokine-mediated inflammation signaling pathways. In particular, we identified a total of 983 DEGs (843 up-regulated; 140 down-regulated) in anorexic cancer compared to controls. A selected number of DEGs including ADAM8, SMAD4, CCR4 and CLU were differentially expressed within cancer group according to the presence/absence of anorexia. In terms of RT-qPCR, ADAM8 was less expressed in cancer patients than controls (p < 0.001), and in anorexic patients vs controls (p = 0.001). The expression of SMAD4 was lower in cancer vs controls (p = 0.005), and in anorexic patients vs controls (p = 0.009). We observed lower CCR4 expression in both anorexic and non-anorexic vs control (p = 0.004, p = 0.011, respectively) and a similar trend was present for CLU. CONCLUSIONS: Our data shed new light on the role of specific genes and their associated molecular pathways as potential key mechanisms for the development of anorexia and may represent a novel landmark for understanding the complex pathophysiology of impaired appetite in cancer.