Building a collaboration to improve surgical research through EORTC/ESSO 1409-CLIMB study: A prospective liver metastasis database with an integrated quality assurance program

The challenges of conducting surgical oncology trials have resulted to low quantity and poor quality research [1,2]. Considering the definitive role of surgery to offer cure, immediate response to improve surgical research is needed [3]. The European Organization for Research and Treatment of Cancer (EORTC) and the European Society of Surgical Oncology (ESSO) share the vision to achieve excellent surgical research and care for cancer patients. Building on their complimentary expertise, they embarked on a pilot project to map out challenges and initiate a sustainable collaboration to advance cancer surgery research in Europe. This pilot project is EORTC-ESSO 1409 GITCG/ ESSO-01: A Prospective Colorectal Liver Metastasis Database with an Integrated Quality Assurance Program (CLIMB). This article will describe the challenges, milestones and vision of both organizations in setting up this collaboration.     

Circulating and skin biopsy-present cytokines related to the pathogenesis of cutaneous lupus erythematosus

Cutaneous lupus erythematosus (CLE) is a common disease that may appear as a separate entity from systemic lupus erythematosus (SLE), precede SLE development, or occur as a manifestation of this systemic disease. It has a complex pathophysiology that involves genetic, environmental, and immune-mediated factors creating a self-amplification pro-inflammatory cycle. CLE is characterized by prominent type I interferons (IFNs) inflammation which are considered as the first precursors of the inflammatory cascade generated within the pathophysiology of CLE. TNF-α enhances the production of antibodies through the activation of B cells, and favors the expression of surface nuclear antigens on keratinocytes. UV light exposure favors keratinocyte apoptosis or necroptosis, which results in the release of multiple proinflammatory cytokines, including IL-6, IL-1α, IL-1β, TNF-α, IFNs, and CXCL10. Serum levels of IL-17 are elevated in patients with ACLE, SCLE, and DLE. Evidence suggests IL-22 plays a role primarily in tissue repair rather than in inflammation. High expression of BAFF and its receptors have been found in lesioned keratinocytes of patients with CLE, and patients with CLE have lower serum levels of the regulatory cytokines TGF-β and IL-10. The chemokines CXCL9 and CXCL10 (CXCR3 ligands) have an increased expression among these patients, and their expression is correlated with IFNs levels. CXCR3 ligands recruit cytotoxic type I cells through this receptor, further supporting the death of keratinocytes via necroptosis with the subsequent release of eNAs perpetuating the inflammatory cycle. Interface dermatitis is characterized by the presence of CXCR3-positive lymphocytes. This review describes the leading cytokines and chemokines present in the circulation and skin that play a fundamental role in the pathogenesis of CLE.     

Exosomes as biomarkers and therapeutic delivery for autoimmune diseases: Opportunities and challenges

Exosomes are spherical lipid bilayer vesicles composed of lipids, proteins and nucleic acids that deliver signaling molecules through a vesicular transport system to regulate the function and morphology of target cells, thereby involving in a variety of biological processes, such as cell apoptosis or proliferation, and cytokine production. In the past decades, there are emerging evidence that exosomes play pivotal roles in the pathological mechanisms of several autoimmune diseases (ADs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes mellitus (T1DM), Sjogren's syndrome (SS), multiple sclerosis (MS), inflammatory bowel disease (IBD). systemic sclerosis (SSc), etc. Several publications have shown that exosomes are involved in the pathogenesis of ADs mainly through intercellular communication and by influencing the response of immune cells. The level of exosomes and the expression of nucleic acids can reflect the degree of disease progression and are excellent biomarkers for ADs. In addition, exosomes have the potential to be used as drug carriers thanks to their biocompatibility and stability. In this review, we briefly summarized the current researches regarding the biological functions of exosomes in ADs, and provided an insight into the potential of exosomes as biomarkers and therapeutic delivery for these diseases.     

Prevention of Clostridium difficile infections—The role of vaccines and therapeutic immunoglobulins

Clostridium difficile is a spore-forming gram-positive bacterium that causes sometimes severe infections of the gut of affected individuals. The high prevalence of C. difficile infections has caused the Center for Disease Control to characterize this disease as “an immediate health threat that requires urgent and aggressive action.” A major issue with existing treatments for C. difficile is their reliance on antibiotics to kill the bacterium. These antibacterial agents cause disruptions in the gut flora that normally compete with C. difficile, rendering the gut lumen susceptible to a new round of infection or to germination of persistent C. difficile spores. This cycle of infection and recurrence underscores the need for novel approaches to the treatment and prevention of C. difficile infections. This review summarizes previous and ongoing efforts to develop active and passive immunization strategies for the prevention of primary and recurrent C. difficile infections.     

A Novel Multiparametric Score for the Detection and Grading of Prosthetic Mitral Valve Obstruction in Cases With Different Disc Motion Abnormalities

Prosthetic mechanical valves are the elective choice in mitral valve (MV) replacement, because of their reliability and easiness of implantation. However, these prostheses can suffer from complications, the major one being prosthetic mitral valve thrombosis (PMVT). In these cases, transthoracic doppler echocardiogram (TDE) is the standard diagnostic workup for diagnosis of valve malfunction. The American Society of Echocardiography (ASE) indicates the possible TDE-derived indexes, which can help in identifying insurgence of MV replacement complications. Unfortunately, in some cases, it is not possible to detect PMVT based on these criteria. In these cases, we speak of Doppler silent thrombosis and only more accurate and invasive analyses, such as fluoroscopy, allow for a correct diagnosis. In this work, computational fluid dynamic models were implemented to simulate valve fluid dynamics in different clinical scenarios in order to improve the reliability of PMVT diagnosis based on TDE. In detail, seven mechanical valve configurations, associated to different potential thrombotic conditions (symmetric and asymmetric stenosis), were designed and tested using five pathologic transmitral velocity profile, extracted from real TDE images; to obtain the flow rate profiles, each TDE velocity profile was scaled to yield a mean flow rate (MFR) of 4, 5 and 6 L/min, respectively. As a result, 105 (7 × 5 × 3) synthetic cases, accounting for different velocity profiles, MFRs and valve configurations, were simulated. TDE-derived indexes were calculated according to the ASE guidelines that were extracted. Advanced statistical methods were applied to propose a new diagnostic algorithm for detecting PMVT. Our results showed that there isn't any significant difference between symmetric and asymmetric stenosis, probe location and flow rate waveform and confirmed that the single modality diagnostic is not able to predict thrombosis in a relevant number of cases, referable to mild and mild-severe stenosis cases. To overcome the problem, a novel multi-parametric discrete score based on the designed diagnostic algorithm was attained and tested; the percentage of stenosis (POS) was predicted with an accuracy rate of 90.5%. Even more interestingly, the error rate of 9.5% is related to four false positive cases corresponding to mild stenosis (POS = 15%) which were erroneously classified as mild-severe stenosis. No false negatives were obtained. Our results suggest that a reliable estimation must take into account the mean flow rate as well as the transmitral velocity profile in order to provide a correct diagnosis.