Histological hallmarks of mucosal healing in inflammatory bowel diseases in the era of monoclonal antibodies therapy: New insights and perspectives

Background: Chronic inflammatory bowel diseases (IBDs) are gaining increasing attention, both because they can severely reduce the quantity and quality of life, and because the advent of monoclonal antibodies has profoundly changed the natural history of these diseases. In recent years, the concept of mucosal healing has assumed a certain importance, and there are more and more clinical and pharmacological trials that consider this parameter among their endpoints, so much so that it may soon be included among the desirable clinical outcomes of patients with IBD. Methods: We performed a literature review of the Pubmed, Medline, and Web of Science (WoS) databases. Results: We selected 88 articles and then removed 6 duplicates; the final sample after accurate application of the inclusion criteria numbered 73 articles, with a level of evidence rating of three or four, according to Oxfords Evidence-based medicine. Our aim was to study the histological impact of monoclonal antibody therapies on mucosal healing, taking into consideration the few studies present in the literature. To perform this review, we compared studies that examined patients with Crohn’s disease (CD) and/or ulcerative colitis (UC) undergoing monoclonal therapy versus patients undergoing other non-biological therapies (PICO statements). Conclusions: We try to delineate how monoclonal antibodies have changed the natural history of IBD, acting at the microscopic level, and we believe that a careful analysis of the histopathology and the definition of the objective criteria for “Mucosa Healing” should enable this concept to be included among the clinical endpoints of patients affected by IBD, thus contributing to a better therapeutic management of these patients

Urological melanoma: A comprehensive review of a rare subclass of mucosal melanoma with emphasis on differential diagnosis and therapeutic approaches

Melanoma is reported as the 19th most common cancer worldwide, with estimated age-standardized incidence rates of 2.8–3.1 per 100,000. Although the origin is most frequently cutaneous, mucosal melanoma has been described several times in literature, and despite its rarity (only 1% of all melanomas), increasing attention is being paid to this disease form. Within this subgroup, melanomas of the uropoetic apparatus are a rarity among rarities. Indeed, less than 50 cases of primary melanoma originating from the urinary bladder have been described, and even less originating from the kidney, renal pelvis and urethra. In this work, we present a detailed review of the literature related to this proaches. subclass of mucosal melanoma, delve into the biological landscape of this neoplasm and discuss current approaches, future perspectives and potential therapeutic approaches. Keywords: melanoma; mucosal melanoma; urology

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

HMGB1-TIM3-HO1: A new pathway of inflammation in skin of SARS-CoV-2 patients? a retrospective pilot study

The SARS-CoV-2 pandemic has completely disrupted the health systems of the entire planet. From the earliest months, it became increasingly clear that in addition to affecting the upper airways and lungs, there were other organs that could be affected. Among these, the skin became a real “sentinel signal” to be able to even suspect COVID-19. Background: this study deals with a little-explored issue for now: the study of skin immunopathology in SARS-CoV-2 positive subjects ascertained using the most reliable methods available. Methods: we used skin biopsy samples from SARS-CoV-2 positive and negative patients, studying morphology (Hematoxylin-Eosin), T lymphocyte population (CD4 and CD8), three markers such as HMGB-1, TIM-3 and HO-1 by immunohistochemistry. Results: although the presence of the CD4 and CD8 T population did not differ statistically significantly, we found greater activation and release of HMGB-1 in skin samples from SARS-CoV-2 positive patients, greater immunolabeling for TIM-3 at the level of CD4 and CD8 and a reduced expression of Heme oxygenase 1. Conclusions: these results support the possibility that there is immune deregulation in SARS-CoV-2 positive patients who develop skin manifestations of various kinds