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/h(2) was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity

Association of NAFLD and Insulin Resistance with Non Metastatic Bladder Cancer Patients: A Cross-Sectional Retrospective Study

Among risk factors (apart from smoking) likely involved in bladder cancer (BCa), metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) have been explored with contrasting results. In spite of these studies, there is little data on the association between nonalcoholic fatty liver disease (NAFLD), its main driver, i.e., insulin resistance (IR), and BCa. Implanting a cross-sectional retrospective study we tried to investigate both NAFLD and IR prevalence in a hospital based population of BCa patients. We studied laboratory data from 204 patients with histologically confirmed non metastatic BCa and 50 subjects with no BCa, but with bladder diseases (no Ca BD). We evaluated the presence of NAFLD by the triglycerides/glucose Index (TyG Index), using a cut-off of 0.59 and by the Aspartate Aminotransferase/Alanine Aminotransferase AST/ALT ratio. IR was assessed by the same TyG Index (cut-off 4.68) and the triglycerides/High-Density Lipoprotein HDL ratio (cut-off 2.197). The diagnosis of impaired fasting glucose (IFG), condition of prediabetes, as well as that of T2DM was assessed according to canonical guidelines. The TyG Index predicted NAFLD presence in both groups (p = 0.000), but the BCa group showed a major percentage of NAFLD cases with respect to no Ca BD group (59% versus 40%). A greater proportion of IR (47%) in BCa group than in no Ca BD one (37%) was evidenced by the TyG Index with its median value significantly different (p = 0.0092). This high rate of IR in the BCa group was confirmed by the triglycerides/HDL ratio (p = 0.02). Prediabetes and T2DM were more prevalent in the BCa group than no Ca BD group (p = 0.024). In this study a consistent NAFLD presence was found in BCa patients. This is an important comorbidity factor that deserves further consideration in prospective studies. The higher prevalence of NAFLD, IR, prediabetes and T2DM in the BCa group evidences the need that these disorders should be reckoned as adjunct factors that could impact on this cancerous disease

Association between growth differentiation factor-15 (GDF-15) serum levels, anorexia and low muscle mass among cancer patients

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 (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 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

EPSILoN score: Validation cohort of a prognostic score in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy

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The Role of Curcumin in Prostate Cancer Cells and Derived Spheroids

A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially avail- able nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moder- ate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids

Novel Key Ingredients in Urinary Tract Health-The Role of D-mannose, Chondroitin Sulphate, Hyaluronic Acid, and N-acetylcysteine in Urinary Tract Infections (Uroial PLUS®)

: Urinary tract infections represent a common and significant health concern worldwide. The high rate of recurrence and the increasing antibiotic resistance of uropathogens are further worsening the current scenario. Nevertheless, novel key ingredients such as D-mannose, chondroitin sulphate, hyaluronic acid, and N-acetylcysteine could represent an important alternative or adjuvant to the prevention and treatment strategies of urinary tract infections. Several studies have indeed evaluated the efficacy and the potential use of these compounds in urinary tract health. In this review, we aimed to summarize the characteristics, the role, and the application of the previously reported compounds, alone and in combination, in urinary tract health, focusing on their potential role in urinary tract infections

Early impairment of food intake in patients newly diagnosed with cancer

BackgroundPatients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis.Patients and methodsPatients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of Anorexia/Cachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels.ResultsOverall, 102 patients [53 male; median age: 67 (range, 21–88) years] were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kg/m2; average percentage of weight loss was 10.1 ± 7.8%. At diagnosis, 68% (69/102) of patients had cachexia, and 11% (11/102) pre-cachexia. Prevalence of anorexia was 57% (58/102) and 75% (76/102) according to FAACT and AQ, respectively. Forty-eight percent (49/102) of patients had hypophagia. Patients with anorexia had lower daily energy (p = 0.002) and protein intake (p = 0.0257), and greater percentage of weight loss (p = 0.0005). In patients with hypophagia, negative correlations were observed between percentage of weight loss and total daily calorie (r = –0.40; p = 0.01) and protein intake (r = –0.340; p = 0.018).ConclusionAnorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed

Radiomics in prostate cancer: an up-to-date review

: Prostate cancer (PCa) is the most common worldwide diagnosed malignancy in male population. The diagnosis, the identification of aggressive disease, and the post-treatment follow-up needs a more comprehensive and holistic approach. Radiomics is the extraction and interpretation of images phenotypes in a quantitative manner. Radiomics may give an advantage through advancements in imaging modalities and through the potential power of artificial intelligence techniques by translating those features into clinical outcome prediction. This article gives an overview on the current evidence of methodology and reviews the available literature on radiomics in PCa patients, highlighting its potential for personalized treatment and future applications

Premature ejaculation in the era of mobile health application: A current analysis and evaluation of adherence to EAU guidelines

Introduction: Several mobile health applications (MHAs) have been developed to assist and improve the quality of life of patients affected by premature ejaculation, but the scientific quality and adherence to guidelines are not yet addressed. Materials and methods: On 25 May 2022, we conducted a search in the Apple App Store and Google Play Store. We reviewed all mobile apps from Apple App Store and Google Play Store for premature ejaculation and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. Results: In total 9 MHA were reviewed. All MHAs are geared towards the patient and provide information about diagnoses and treatment of PE. The mean score were 2.87, 3.69, 2.77, 2.55, 2.86 for Engagement, Functionality, Aesthetics, Information, and Subjective quality respectively. MHAs reported low and medium adherence to EAU guidelines. Conclusions: MHAs provide different services in many medical fields, including male sexual dysfunction. Their development is constantly increasing, but the problems of scientific validation, content, and quality are not yet solved. Much future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps