COVID-19 and lung cancer: risks, mechanisms and treatment interactions.

Cases of the 2019 novel coronavirus also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to rise worldwide. To date, there is no effective treatment. Clinical management is largely symptomatic, with organ support in intensive care for critically ill patients. The first phase I trial to test the efficacy of a vaccine has recently begun, but in the meantime there is an urgent need to decrease the morbidity and mortality of severe cases. It is known that patients with cancer are more susceptible to infection than individuals without cancer because of their systemic immunosuppressive state caused by the malignancy and anticancer treatments. Therefore, these patients might be at increased risk of pulmonary complications from COVID-19. The SARS-CoV-2 could in some case induce excessive and aberrant non-effective host immune responses that are associated with potentially fatal severe lung injury and patients can develop acute respiratory distress syndrome (ARDS). Cytokine release syndrome and viral ARDS result from uncontrolled severe acute inflammation. Acute lung injury results from inflammatory monocyte and macrophage activation in the pulmonary luminal epithelium which lead to a release of proinflammatory cytokines including interleukin (IL)-6, IL-1 and tumor necrosis factor-α. These cytokines play a crucial role in immune-related pneumonitis, and could represent a promising target when the infiltration is T cell predominant or there are indirect signs of high IL-6-related inflammation, such as elevated C-reactive protein. A monoclonal anti-IL-6 receptor antibody, tocilizumab has been administered in a number of cases in China and Italy. Positive clinical and radiological outcomes have been reported. These early findings have led to an ongoing randomized controlled clinical trial in China and Italy. While data from those trials are eagerly awaited, patients' management will continue to rely for the vast majority on local guidelines. Among many other aspects, this crisis has proven that different specialists must join forces to deliver the best possible care to patients

Gender-specific aspects of epidemiology, molecular genetics and outcome: lung cancer.

Lung cancer remains the leading cause of cancer-related deaths worldwide in women and men. In incidence, lung cancer ranks second, surpassed by breast cancer in women and prostate cancer in men. However, the historical differences in mortality and incidence rate between both sexes have changed in the last years. In the last decades, we have also witnessed an increased number of lung cancer in female never-smokers. These disparities have grown our interest in studying the impact of the gender and sex in the presentation of lung cancer. The aetiology is yet to be fully elucidated, but the data are clear so far: there is a growing divide between lung cancer presentation in women and men that will change our management and study of lung cancer. This article aims to review the sex and gender differences in lung cancer

Novel targets for immune-checkpoint inhibition in cancer.

Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer. We highlight their biology, emphasizing the current understanding of resistance mechanisms and focusing on promising strategies that are under investigation. We also summarize current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients

Kinetics of Formation of Butyric and Pyroglutamic Acid during the Shelf Life of Probiotic, Prebiotic and Synbiotic Yoghurt

Butyric acid (C4) and pyroglutamic acid (pGlu) exert significant beneficial effects on human health. In this study, the influence of probiotics (Lactobacillus acidophilus and Bifidobacteria) and/or prebiotics (1 and 3% inulin and fructo-oligosaccharides) on the content of C4 and pGlu in yoghurt during the shelf-life period was evaluated. The contents of C4 and pGlu were determined in probiotic, prebiotic and synbiotic yoghurts during 30 days of storage at 4 ◦C by solid-phase microextraction coupled with gas chromatography/mass spectrometry and HPLC analysis. Traditional yoghurt and uninoculated milk were used as control. Prebiotic yoghurt contained more C4 (2.2–2.4 mg/kg) than the uninoculated milk, and no increase was detected with respect to traditional yoghurt. However, probiotic yoghurt showed 10% more C4 than traditional yoghurt. Adding fibre to probiotics (synbiotic yoghurt) the C4 content increased by 30%. Regarding pGlu, probiotic yoghurt presented the highest content of approximately 130 mg/100 g. Fibre did not affect pGlu content. Finally, C4 and pGlu contents generally increased up to 20 days of storage and then decreased up to 30 days of storage. The results might be useful for the preparation of other functional foods rich in C4 and pGlu using lactic acid bacteria

Proteomic study of muscle sarcoplasmic proteins using AUT-PAGE/SDS-PAGE as two-dimensional gel electrophoresis

The conversion of muscle to meat in pig involves mainly proteolysis of myofibrillar proteins, which undergo notable changes since early stage of rigor mortis, even after 48 h post mortem. The tenderness of meat has been thoroughly investigated to understand the biochemical mechanisms, which influence texture and flavour development as well as the technological parameters and hence meat quality. Cytoplasmic proteolytic calcium dependent enzymes, named -and m-calpains, which act in the early stages of rigor mortis, significantly contribute to tenderization weakening myofibrils. These enzymes, however, act for fewdays because they are specifically inhibited by calpastatin and by pH lowering. However, when pH falls to about 5.0, proteolytic activity on muscle proteins is continued by longer acting lysosomal proteinase, cathepsins [3,7–9]. Post mortem proteolysis also causes relevant changes in sarcoplamic protein fraction, which represent the water soluble fraction (quantitatively about 30–35%) of meat total protein, and the involved proteins has already been identified by proteomic-based studies. Recent investigations have demonstrated that the most commonly found Lactobacillus species in dry fermented meats are able to hydrolyse myofibrillar and sarcoplasmic muscle proteins in vitro.The most abundant sarcoplasmic proteins, as mixture of basic polypeptides with a narrow spread range of molecular masses, represented an excellent model to test our analytical technique and to delineate its capabilities. In the present study, we compared 2D AUT-PAGE/SDSPAGE maps of water-soluble proteins extracted from fresh meat and from dry-cured ham, a non fermented product, from “Naples-type” salami, a microbiologically fermented product, and from “Coppa”, a typical semi-fermented product. Electrophoretically separated proteins have been identified by MALDI-ToF mass fingerprinting

Antimicrobial activity of lipids extracted from Hermetia illucens reared on different substrates

Abstract: As the problem of antimicrobial resistance is constantly increasing, there is a renewed interest in antimicrobial products derived from natural sources, particularly obtained from innovative and eco-friendly materials. Insect lipids, due to their fatty acid composition, can be classified as natural antimicrobial compounds. In order to assess the antibacterial efficacy of Hermetia illucens lipids, we extracted this component from the larval stage, fed on different substrates and we characterized it. Moreover, we analyzed the fatty acid composition of the feeding substrate, to determine if and how it could affect the antimicrobial activity of the lipid component. The antimicrobial activity was evaluated against Gram-positive Micrococcus flavus and Gram-negative bacteria Escherichia coli. Analyzing the fatty acid profiles of larval lipids that showed activity against the two bacterial strains, we detected significant differences for C4:0, C10:0, C16:1, C18:3 n3 (ALA), and C20:1. The strongest antimicrobial activity was verified against Micrococcus flavus by lipids extracted from larvae reared on strawberry, tangerine, and fresh manure substrates, with growth inhibition zones ranged from 1.38 to 1.51 mm, while only the rearing on manure showed the effect against Escherichia coli. Notably, the fatty acid profile of H. illucens seems to not be really influenced by the substrate fatty acid profile, except for C18:0 and C18:2 CIS n6 (LA). This implies that other factors, such as the rearing conditions, larval development stages, and other nutrients such as carbohydrates, affect the amount of fatty acids in insects. Key points: • Feeding substrates influence larval lipids and fatty acids (FA) • Generally, there is no direct correlation between substrate FAs and the same larvae FAs • Specific FAs influence more the antimicrobial effect of BSF lipids Graphical abstract: [Figure not available: see fulltext.

Two Case Reports of Biliary Tract Injuries during Laparoscopic Cholecystectomy

Background and Study Aims. Biliary tract injuries (BTI) represent the most serious and potentially life-threatening complication of cholecystectomy occurring also during laparoscopic approaches. Patients and Methods. We describe and discuss two different cases of BTI occurring during laparoscopic cholecystectomy (LC). Results. Two patients developed BTI during LC and one evidenced the complication during the LC itself and was treated during the same LC in real time. The other patient evidenced BTI only after the primary intervention and was successfully reoperated in laparotomy after 10 days from the LC. Conclusions. The factors that predispose to the occurrence of BTI during cholecystectomy and the cautions to be used to prevent BTI are discussed

Blood profile and productive performance after partial substitution of maize grain with ancient wheat lines by-products in organic laying hens' diet

The aim of this research was to evaluate the effects of the partial substitution of maize grain with local ancient wheats by-products in an organic laying hens farm on animal performance and blood profile, as well as on eggs quality. A total of 80 Hy-Line W-36 Single Comb White Leghorn, 18 weeks old hens were homogenously divided into two groups. The two groups (40 laying hens each, 8 replicates, 5 hens/replicate) were fed two isoprotein and isoenergetic diets: the Control group (C) was fed a standard, organic maize-soybean meal diet whereas in the Ancient Grains group (AG) part of the maize grain was replaced by a mix of ancient grains middling, consisting in 50:50 of Triticum aestivum var. spelta (spelt) and Triticum durum dicoccum L. (emmer wheat). The birds fed the maize based-diet (C) showed a higher (P < 0.01) egg weight and feed intake than the Ancient Grains (AG) group. By contrary, the feed conversion ratio was more favourable (P < 0.05) in hens fed the Ancient Grains diet. The eggs produced by the hens fed the Control diet showed higher length and width than the other group (P < 0.01). The shell thickness and strength were also higher in the Control group (P < 0.01 and P < 0.05, respectively). The experimental dietary treatment positively affected some blood parameters. The Control group showed higher levels of cholesterol and triglycerides (P < 0.05) as well as of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) (P < 0.01). In addition, butyrate, which may have great implications for the regulation of the immune response, resulted significantly higher in the caecal content of hens from the Ancient Grains group. Overall, the Ancient Grains diet seemed to be able to guarantee the production performances with positive effects on the animal health

Quality of Life in Patients With Severe Skin Reactions in Course of First-Generation Epidermal Growth Factor Receptor Inhibitors Monoclonal Antibodies (Our Experience With Cetuximab)

Background: Metastatic colorectal cancer (mCRC) with wild type expression of RAS and RAF genes can be treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, such as cetuximab, in combination with chemotherapy. Skin toxicity represents the most serious and frequent side effect in these patients. Skin manifestations occur in approximately 80% of patients. In this study, we investigated the consequences on body image and quality of life (QoL) of patients with severe skin toxicity. Methods: One hundred patients were enrolled with mCRC. All patients signed informed consent and completed questionnaires to assess QoL and body discomfort. Toxicity was assessed on Common Terminology Criteria for Adverse Events (CTCAEs). Results: The greatest impact on QoL was represented by difficulties in managing skin rash-related side effects. Data showed a significant impact in psychological sphere and social relationships. Conclusions: Skin side effects, particularly rash, influence QoL and social relationships, compromising therapeutic compliance