Tranexamic acid in Neurosurgery: a controversy indication—review

Neurosurgical Review - Tranexamic acid (TXA) is one of the measures indicated to reduce bleeding and the need for volume replacement. However, data on risks and benefits are controversial. This...     

Generation of multiepitope cancer vaccines based on large combinatorial libraries of survivin-derived mutant epitopes

Immune tolerance is the main challenge in the field of cancer vaccines, so modified peptide sequences or naturally occurring mutated versions of cancer-related wild-type (WT) antigens represent a promising pathway. However, the low immunogenicity of mutation-induced neoantigens and, particularly, their incapacity to activate CD8⁺ T cells are generating doubts on the success of neoantigen-based cancer vaccines in clinical trials. We developed a novel vaccine approach based on a new class of vaccine immunogens, called variable epitope libraries (VELs). We used three regions of survivin (SVN), composed of 40, 49 and 51 amino acids, along with the complete SVN protein to generate the VELs as multiepitope vaccines. BALB/c mice, challenged with the aggressive and highly metastatic 4T1 cell line, were vaccinated in a therapeutic setting. We showed significant tumor growth inhibition and, most importantly, strong suppression of lung metastasis after a single immunization using VEL vaccines. We demonstrated vaccine-induced broad cellular immune responses concomitant with extensive tumor infiltration of T cells, the activation of CD107a⁺ IFN-γ⁺ T cells in the spleen and a significant increase in the number of CD3⁺ CD8⁺ Ly6C⁺ effector T cells. In addition, we observed the presence of interferon-γ-, granzyme B- and perforin-producing lymphocytes along with modifications in the amount of CD11b⁺ Ly6C^int/low Ly6G⁺ granulocytic myeloid-derived suppressor cells and CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells in the lungs and tumors of mice. In summary, we showed that the VELs represent a potent new class of cancer immunotherapy and propose the application of the VEL vaccine concept as a true alternative to currently available vaccine platforms.     

Relative age effect and left-handedness in world class water polo male and female players

Most studies of the relative age effect (RAE) refer to popular sports. In contrast, we examined to what extent the RAE is present in elite water polo players, as well as the association between handedness and RAE. For these purposes, laterality, anthropometry, month of birth, performance and playing position of participants in the 2011, 2013 and 2015 World Championships (623 women, 622 men) were analised. No RAE was observed in the total sample. However, the proportion of male left-handed field players born in the first quarter (11%) was lower than those born in the second (35.3%) and fourth quarter (29.4%). Regarding the overall laterality, the amount of left handed players was similar to the general population (10%). Nevertheless, there was a larger amount of left-handed wings than expected both in men (23.7%) and women (34.4%). Left-handed male players performed more shots, shots/minute and also scored more goals than right-handed players. Women left-handed players were younger and they performed more shots/minute. There is no RAE in elite male and female water polo players. However, laterality could be a possible moderator of the RAE particularly in left handed players, which should be taken into account in future studies.     

Impaired cellular and humoral immunity is a feature of Diamond-Blackfan anaemia; experience of 107 unselected cases in the United Kingdom

Diamond-Blackfan anaemia (DBA) is a rare bone marrow failure syndrome characterised by anaemia, congenital anomalies and cancer predisposition. Although infections are the second leading cause of mortality in non-transplanted patients, immune function is largely unexplored. We identified quantitative deficits in serum immunoglobulins and/or circulating T, natural killer and B lymphocytes in 59 of 107 unselected patients (55·1%) attending our centre over a 7-year period. Immune abnormalities were independent of ribosomal protein genotype and arose in both steroid-treated and steroid-untreated patients. In summary, these data highlight the high prevalence and spectrum of infections and immune defects in DBA.     

Growth Factors as Treatment for Inflammatory Bowel Disease: A Concise Review of the Evidence Toward Their Potential Clinical Utility

In the process of inflammation and repair of the intestinal mucosa in inflammatory bowel disease (IBD), there occurs a complex and an unknown interplay of innate and adaptive immune mechanisms. This interaction of factors may explain why IBD is characterized by a relapsing and remitting clinical course. Different components of innate immunity, hormones and interleukins in IBD have been suggested to be impaired. The growth hormone, epidermal growth factor, keratinocyte growth factor and colony-stimulating factors have emerged as potential tools for the modulation of intestinal inflammation and repair. Despite promising results of initial studies, the evidence that justify treatment of patients in clinical practice is not enough as some of the trials are nonrandomized or included a small number of patients. In this concise review, we provide a summary of the most recent and relevant evidence regarding the potential therapeutic effects of growth factors in IBD.     

Identification and management of HNPCC syndrome (hereditary non polyposis colon cancer), hereditary predisposition to colorectal and endometrial adenocarcinomas

BACKGROUND: The HNPCC syndrome (hereditary non polyposis colon cancer) is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for small intestine, urothelial, ovary, stomach and biliary tract carcinomas. HNPCC syndrome is responsible for 5% of colorectal cancers. Identification and management of this disease are part of a multidisciplinary procedure. METHODS: 12 experts have been mandated by the French Health Ministry to analyze and synthesize their consensus position, and the resulting document has been reviewed by an additional group of 4 independent experts. MAIN RECOMMENDATIONS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a 2-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks, but other organs being at low lifetime risk, no specific surveillance will be proposed.