Microbiota-Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies.

Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral-gastric-gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral-gastric-gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC.

Metabolic Disorders and Psoriasis: Exploring the Role of Nutritional Interventions.

(1) Background: Psoriasis is a chronic autoimmune disease with a close relationship with metabolic diseases such as obesity, diabetes, and dyslipidemia. The aim of this review was to identify the relationship between psoriasis, metabolic diseases, and dietetic therapies. According to recent findings, there is a strong association between psoriasis and obesity as well as vitamin D and micronutrient deficiencies. (2) Methods: This review was conducted via PubMed, aiming to search for studies involving psoriasis linked with metabolic disorders or with nutritional treatments. (3) Results: Our review shows that a healthy lifestyle can positively influence the course of the disease. The maintaining of a proper body weight together with physical activity and good nutritional choices are associated with an improvement in psoriasis severity. A Mediterranean diet rich in fiber, vitamins, and polyphenols may indeed be a strategy for controlling psoriasis symptoms. The effectiveness of this diet lies not only in its anti-inflammatory power, but also in its ability to favorably influence the intestinal microbiota and counteract dysbiosis, which is a risk factor for many autoimmune diseases. (4) Conclusions: In synergy with standard therapy, the adoption of an appropriate diet can be recommended to improve the clinical expression of psoriasis and reduce the incidence of comorbidities.

Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota.

Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis and their deficiency is involved in the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, and cardiometabolic disorders. SCFAs are metabolites of specific bacterial taxa of the human gut microbiota, and their production is influenced by specific foods or food supplements, mainly prebiotics, by the direct fostering of these taxa. This Review provides an overview of SCFAs' roles and functions, and of SCFA-producing bacteria, from their microbiological characteristics and taxonomy to the biochemical process that lead to the release of SCFAs. Moreover, we will describe the potential therapeutic approaches to boost the levels of SCFAs in the human gut and treat different related diseases.

Lipid-Enriched Parenteral Nutrition and Bloodstream Infections in Hospitalized Patients: Is It a Real Concern?

Today, few clinicians are still convinced that lipids are sepsis risk factors in patients receiving parenteral nutrition. This dogma is principally based on old literature. This review deals with the most recent literature search that provided up-to-date data over the past ten years. Systematic research was performed on Pubmed, MEDLINE, and Web of Science. The recent evidence does not justify the exclusion of lipid emulsions in patients receiving parenteral nutrition for fear of bloodstream infection risk. Moreover, lipids represent a substantial proportion of the energy source providing essential fatty acids, potentially improving clinical outcomes in patients often malnourished. Understanding the actual risk factors of sepsis during parenteral nutrition is necessary to optimize patient nutritional status and care and avoid essential fatty acid deficiency. There is an urgent need to make updated nutrition training available at all levels of medical education.

The prognostic value of skeletal muscle index on clinical and survival outcomes after cytoreduction and HIPEC for peritoneal metastases from colorectal cancer: A systematic review and meta-analysis.

BACKGROUND: Cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) represent the most effective strategy to manage peritoneal metastases (PM). This systematic review and meta-analysis aimed to assess the impact of body composition on clinical outcomes in patients with PM. METHODS: A systematic literature search was performed using Medline, Web of Science and EMBASE databases from inception to the 20st August 2020. Data were independently extracted by 3 authors. Newcastle-Ottawa Scale was used to assess quality and risk of bias of studies. Pooled analyses were performed using Mantel-Haenszel method to estimate overall effect size with mean differences or odd ratios (ORs) and 95% confidence interval (CI). The primary outcome was postoperative complication (POC) rate, while secondary outcomes were severe POC and postoperative mortality. RESULTS: A total of 4 studies were included in the systematic review and meta-analysis, including 582 patients. A significant association between low skeletal muscle mass and POC was found (OR 1.45, 95% CI 1.04 to 2.03; p = 0.03), while no differences were found in terms operative time, estimated blood loss, length of hospital stay, and postoperative mortality (p > 0.05). CONCLUSIONS: Low skeletal muscle mass at diagnosis is a valid prognostic factor for POC development in colorectal and PM patients undergoing CRS. Prospective and larger studies are needed to better investigate the role of CT scan derived body composition and to understand how to implement this tool in clinical practice.

Neoadjuvant treatment: A window of opportunity for nutritional prehabilitation in patients with pancreatic ductal adenocarcinoma.

Patients affected by pancreatic ductal adenocarcinoma (PDAC) frequently present with advanced disease at the time of diagnosis, limiting an upfront surgical approach. Neoadjuvant treatment (NAT) has become the standard of care to downstage non-metastatic locally advanced PDAC. However, this treatment increases the risk of a nutritional status decline, which in turn, may impact therapeutic tolerance, postoperative outcomes, or even prevent the possibility of surgery. Literature on prehabilitation programs on surgical PDAC patients show a reduction of postoperative complications, length of hospital stay, and readmission rate, while data on prehabilitation in NAT patients are scarce and randomized controlled trials are still missing. Particularly, appropriate nutritional management represents an important therapeutic strategy to promote tissue healing and to enhance patient recovery after surgical trauma. In this regard, NAT may represent a new interesting window of opportunity to implement a nutritional prehabilitation program, aiming to increase the PDAC patient's capacity to complete the planned therapy and potentially improve clinical and survival outcomes. Given these perspectives, this review attempts to provide an in-depth view of the nutritional derangements during NAT and nutritional prehabilitation program as well as their impact on PDAC patient outcomes.

Nutritional Interventions Targeting Gut Microbiota during Cancer Therapies.

The gut microbiome is increasingly being recognized for its influence on intestinal and extra-intestinal disorders such as cancer. Today, diet is the most studied environmental modulator of gut microbiota, capable of altering or improving it in terms of richness and diversity. Recent evidence from several preclinical and clinical trials suggested that gut microbiota composition could modulate cancer therapies (toxicities, treatment responses) and vice versa. This review highlights the latest research on the bidirectional associations between gut microbiota and cancer. We also dissect the role of gut microbiota during cancer therapies in terms of toxicity and treatment response and, in turn, how cancer therapies could impact gut microbiota composition and functions. In this context, we summarize the state-of-the-art research regarding the role of various nutritional interventions-prebiotics, dietary strategies, and dietary restrictions-as cutting-edge possibilities to modulate gut microbiota during cancer therapies.

Prognostic value of skeletal muscle mass during tyrosine kinase inhibitor (TKI) therapy in cancer patients: a systematic review and meta-analysis.

Low muscle mass has been associated with worse clinical outcomes in various cancers. This work investigated whether, during tyrosine kinases inhibitors (TKIs) therapy, low muscle mass was associated with treatment toxicity and survival outcomes. A systematic literature search was performed in Pubmed, Web of Science, and Scopus databases from inception to June 2020, based on fixed inclusion and exclusion criteria. Effect sizes were estimated with hazard ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) and heterogeneity was assessed by measuring inconsistency (I2) based on the Chi squared test. A total of 24 retrospective studies were identified, enrolling patients treated with sorafenib (n = 12), sunitinib (n = 6), lenvatinib (n = 3), regorafenib (n = 2), gefitinib (n = 1), imatinib (n = 1), and pazopanib (n = 1). Thirteen studies were deemed eligible for pooled analyses. Meta-analyses found a significant effect of low muscle mass on dose-limiting toxicity (DLT) (OR 2.40, 95% CI 1.26-4.58, p = 0.008, I2 = 51%) in patients treated with TKI therapy. A subgroup analysis by treatment showed an association between DLT and low muscle during sorafenib or sunitinib, although not significant. A significant association between low skeletal muscle index and poorer overall survival was observed in HCC patients treated with sorafenib (HR 1.45, 95% CI 1.07-1.96, p = 0.02). For other TKIs, although some results showed an association between low muscle mass and worse outcomes, the number of studies for each TKI therapy was too small to reach conclusions. Skeletal muscle mass could influence the prognosis of some TKI-treated patients. This effect is demonstrated in sorafenib-treated HCC patients but remains almost unexplored in other cancer patients undergoing TKI therapy. Further prospective studies with large sample size and sufficient follow-up are needed to clarify the role of muscle mass in the metabolism of TKI-based cancer treatment, and its association with toxicity and survival.

Food Additives, Gut Microbiota, and Irritable Bowel Syndrome: A Hidden Track.

The interactions between diet, gut microbiota, and irritable bowel syndrome (IBS) have many complex mechanisms that are not fully understood. Food additives are one component of the modern human diet that deserves attention from science and government policies. This review aims at identifying the current knowledge about the impact of food additives on gut microbiota and their potential role in the development of IBS. To date, few data on the effect of food additives on gut microbiota in IBS patients are available. However, exposure to food additives could induce the dysbiosis and dysregulation of gut homeostasis with an alteration of the gut barrier and activation of the immune response. These microbial changes could exacerbate the gut symptoms associated with IBS, such as visceral pain, low-grade inflammation, and changes in bowel habits. Some additives (polyols) are excluded in the low fermentable oligo-, di- and monosaccharide, and polyol (FODMAP), diets for IBS patients. Even if most studies have been performed in animals, and human studies are required, many artificial sweeteners, emulsifiers, and food colorants could represent a potential hidden driver of IBS, through gut microbiota alterations. Consequently, food additives should be preventively avoided in the diet as well as dietary supplements for patients with IBS.

Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges.

In cancer patients, loss of muscle mass is significantly associated with low tolerability of chemotherapy and poor survival. Despite the great strides in the treatment of cancer, targeted therapies such as tyrosine kinase inhibitors (TKIs) could exacerbate muscle wasting. Over recent years, the impact of skeletal muscle loss during TKI therapy on clinical outcomes has been in the spotlight. In this review, we focus on the different molecular pathways of TKIs potentially involved in muscle wasting. Then, we report the results of the studies assessing the effects of different TKI therapies-such as sorafenib, regorafenib, sunitinib, and lenvatinib-on muscle mass, and highlight their potential clinical implications. Finally, we discuss an integrative nutritional approach to be adopted during TKI treatment. The assessment of muscle mass from computerized tomography imaging could be helpful in predicting toxicity and prognosis in patients treated with TKI such as sorafenib. Early recognition of low muscle mass and effective personalized nutritional support could prevent or attenuate muscle mass wasting. However, the role of nutrition is still overlooked, and future clinical trials are needed to find the optimal nutritional support to countermeasure muscle mass depletion during TKI therapy.

The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: results from the NutriCatt protocol.

BACKGROUND: Malnutrition in liver surgery is correlated with higher postoperative complications and longer length of hospital stay (LOHS), the same items that ERAS programs try to optimize. However, to date, standardized dietary protocols have not been defined within ERAS programs. Aim of this study was to evaluate the impact on LOHS and postoperative complications, of a personalized nutritional protocol (NutriCatt) with diet and oral branched-chain amino acid (BCAA) supplementation, adopted within the ERAS program. METHODS: 1960 consecutive liver resections were performed from January 2000 to September 2018. EXCLUSION CRITERIA: perihilar cholangiocarcinoma, simultaneous colorectal and liver resections. Four groups for analysis: resections before 2009 (1st period); from 2009 to 2016 (2nd period, including laparoscopic resections); between 2016 and September 2017 (ERAS); after September 2017 (ERAS + NutriCatt). RESULTS: LOHS declined (p < 0.0001), from a median of 10 days (1st period) to 8, 7 and 6 in 2nd period, ERAS and ERAS + NutriCatt groups, respectively. At multivariable analysis for risk of LOHS > 8 days, the 2nd period, ERAS and ERAS + NutriCatt groups showed a protective effect. These results were confirmed for both minor and major resections. LOHS was significantly lower in ERAS + Nutricatt group than in ERAS group, without increasing risk of postoperative complications, although the rate of laparoscopic resections was similar in these two groups and complexity of liver resections was significantly higher in the last period. CONCLUSIONS: Adoption of a personalized nutritional protocol with BCAA supplementation within the ERAS program for liver resections was a safe and effective approach that may impact on reducing the LOHS.

TACE with degradable starch microspheres (DSM-TACE) as second-line treatment in HCC patients dismissing or ineligible for sorafenib.

OBJECTIVES: To date, there is no approved second-line treatment for patients dismissing sorafenib or ineligible for this treatment, so it would be useful to find an effective alternative treatment option. The aim of our study was to evaluate safety, feasibility and effectiveness of transarterial chemoembolisation with degradable starch microspheres (DSM-TACE) in the treatment of patients with advanced hepatocellular carcinoma (HCC) dismissing or ineligible for multikinase-inhibitor chemotherapy administration (sorafenib) due to unbearable side effects or clinical contraindications. METHODS: Forty consecutive BCLC stage B or C patients (31 male; age, 70.6 ± 13.6 years), with intermediate or locally advanced HCC dismissing or ineligible for sorafenib administration, who underwent DSM-TACE treatment cycle via lobar approach were prospectively enrolled. Tumour response was evaluated on multidetector computed tomography based on mRECIST criteria. Primary endpoints were safety, tolerance and overall disease control (ODC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Technical success was achieved in all patients. No intra/peri-procedural death/major complications occurred. No signs of liver failure or systemic toxicity were detected. At 1-year follow-up, ODC of 52.5% was registered. PFS was 6.4 months with a median OS of 11.3 months. CONCLUSIONS: DSM-TACE is safe and effective as a second-line treatment in HCC patients dismissing or ineligible for sorafenib. KEY POINTS: • DSM-TACE is safe and effective as second-line treatment in HCC patients dismissing or ineligible for sorafenib • DSM-TACE allows the temporary occlusion of the smaller arterial vessels, improving overall therapeutic effectiveness by reducing the immediate wash-out of the cytostatic agent • DSM-TACE also decreases the risk of systemic toxicity and post-embolic syndrome.

The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut⁻Retina Axis.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30⁻50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Hypokalemia-induced pseudoischemic electrocardiographic changes and quadriplegia.

Hypokalemia is a common biochemical abnormality. Severe hypokalemia can produce cardiac rhythm alterations and neurologic manifestations. Early detection and treatment allow clinician to prevent morbidity and mortality from cardiac arrhythmias and respiratory failure. Here, we describe a case of severe hypokalemia inducing pseudoischemic electrocardiographic (ECG) alterations and quadriplegia, in a patient affected by chronic diarrhea. Electrocardiographic alterations and neurologic manifestations completely disappeared after potassium replacement; however, prolonged potassium supplementation was required to achieve the normalization of plasmatic potassium levels. Consecutive figures show ECG improvement until normalization of ECG findings.