Gut mesenchymal stromal cells in immunity

Mesenchymal stromal cells (MSCs), first found in bone marrow (BM), are the structural architects of all organs, participating in most biological functions. MSCs possess tissue-specific signatures that allow their discrimination according to their origin and location. Among their multiple functions, MSCs closely interact with immune cells, orchestrating their activity to maintain overall homeostasis. The phenotype of tissue MSCs residing in the bowel overlaps with myofibroblasts, lining the bottom walls of intestinal crypts (pericryptal) or interspersed within intestinal submucosa (intercryptal). In Crohn’s disease, intestinal MSCs are tightly stacked in a chronic inflammatory milieu, which causes their enforced expression of Class II major histocompatibility complex (MHC). The absence of Class II MHC is a hallmark for immune-modulator and tolerogenic properties of normal MSCs and, vice versa, the expression of HLA-DR is peculiar to antigen presenting cells, that is, immune-activator cells. Interferon gamma (IFN) is responsible for induction of Class II MHC expression on intestinal MSCs. The reversal of myofibroblasts/MSCs from an immune-modulator to an activator phenotype in Crohn’s disease results in the formation of a fibrotic tube subverting the intestinal structure. Epithelial metaplastic areas in this context can progress to dysplasia and cancer

Ambulatory surgery for perianal Crohn’s disease. Study of feasibility

Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications

Impact of a multidisciplinary approach in enteropathic spondyloarthritis patients

Spondyloarthritis (SpA) and inflammatory bowel disease (IBD) are chronic autoinflammatory diseases that partially share the genetic predisposition and the unchecked inflammatory response linking the gut to the joints. The coexistence of both conditions in patients and the increased cross-risk ratios between SpA and IBD strongly suggest a shared pathophysiology. The prevalence of Enteropathic-related Spondyloarthritis (ESpA) in IBD patients shows a wide variation and may be underestimated. It is well accepted that the management of joint pain requires rheumatological expertise in conjunction with gastroenterologist assessment. In this view, we aimed at assessing, in a prospective study performed in a combined Gastro-Intestinal and Rheumatologic "GI-Rhe" clinic: (1) the prevalence of ESpA and other rheumatologic diseases in IBD patients with joint pain; (2) the features of the ESpA population; and (3) the diagnostic delay and the potential impact of the combined assessment. From November 2012 to December 2014, IBD patients with joint pain referring to a dedicated rheumatologist by the IBD-dedicated gastroenterologist were enrolled. Clinical and biochemical evaluations, joint involvement and disease activity assessment, diagnostic delay, and treatment were recorded. IBD patients (n = 269) with joint pain were jointly assessed in the "GI-Rhe" Unit. A diagnosis of ESpA was made in 50.5% of IBD patients with joint pain. ESpA patients showed a peripheral involvement in 53% of cases, axial in 20.6% and peripheral and axial in 26.4% of cases. ESpA patients had a higher prevalence of other autoimmune extra-intestinal manifestations and received more anti-TNF treatment compared with IBD patients. A mean diagnostic delay of 5.2. years was revealed in ESpA patients. Patients with joint disease onset in the 2002-2012 decade had reduced diagnostic delay compared with those with onset in the 1980-1990 and 1991-2001 decades. Diagnostic delay was further reduced for patients with joint onset in the last two years in conjunction with the establishment of the GI-Rhe clinic. Multidisciplinary approach improved management of rheumatic disorders in IBD patients allowing a more comprehensive care

Female Roles in Antiquity: The Dichotomy Between the Stage and the Page

The women portrayed in Greek drama were often strong, courageous, and integral to the storyline. In contrast to their real-life counterparts (who may have not even been allowed to see the plays), these women stood out as individuals in their respective stories. They are bold, dynamic, intelligent and respected. They are meant to be seen and heard. Women in drama emerge as heroines of their own stories and serve to educate the audience on some aspect of women in Greece. On other hand, the women of Homeric epics tended to be subdued and traditional; they are background characters, merely present to help or hinder their heroes. The women in these poems are meant to serve a teaching purpose as well; they taught women how they should and should not strive to be. Both the stage and the page provide great insight into the expectations and realities of women in antiquity

Mary Todd Lincoln: Duty and Depression

First Lady Mary Todd Lincoln was perceived by Victorian America as materialistic and unbalanced. Behind the closed doors of the Executive Mansion, however, lie a grief-stricken mother struggling to manage an undiagnosed and untreated mental illness. Her fragile condition was exacerbated with each death of her beloved family. Yet, this First Lady played an integral role in the White House, acting as hostess, advisor to the President, and activist in her own right. She was not a passive bystander as her husband worked tirelessly to preserve the Union, but an active participant in the war effort. Following Abraham Lincoln’s premature demise, Mary Lincoln’s internal battle amplified tenfold. The devastated widow’s mental well-being continued to rapidly decline until her death. Despite her handicap, Mary became the sole custodian of the Lincoln legacy and worked determinedly to honor his memory and wishes. After her time as First Lady came to an abrupt end, Mary continued to lobby for the lavish lifestyle she believed the wife of Lincoln deserved. She became an advocate of widow’s rights, especially when it came to bereavement pensions. While battling her inner demons Mary Lincoln battled the Democrats, Confederates, Radical Republicans, her own family, and the American people. Despite her external traumas and internal turmoil, Mary Todd Lincoln was an active and trendsetting First Lady both during and after her tenure at the White House

Pretransplant identification of acute rejection risk following kidney transplantation

Lack of an accepted definition for 'high immunological risk' hampers individualization of immunosuppressive therapy after kidney transplantation. For recipient-related risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor. Conventional immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant anti-HLA alloantibodies, and panel reactive antibodies) are being reassessed in light of growing understanding about the role of donor-specific antibodies (DSA). At the time of transplant, delayed graft function is one of the most clear-cut risk factors for acute rejection. Extended cold ischemia time (≥24 h) may also play a contributory role. While it is not yet possible to establish conclusively the relative contribution of different risk factors for acute rejection after kidney transplantation, the available data point to variables that should be taken into account at the time of transplant. Together, these offer a realistic basis for planning an appropriate immunosuppression regimen in individual patients