Background and aims IBD can impair the patients` functional capacity with significant negative effects on their quality of life. Our aim was to determine the impact of IBD diagnosis on fitness levels and to assess the levels of engagement in physical activity and fatigue in IBD patients` pre-and post-diagnosis. Methods A prospective multi-centre cross-sectional study was performed. Patients diagnosed with IBD in the previous 18 months were recruited. Inclusion criteria included clinical remission and/or no treatment changes within the previous 6 months. Physical exercise levels were assessed by the Godin score and fatigue levels was assessed by the Functional assessment of chronic illness therapy (FACIT) score. Results 158 patients (100 CD) were recruited. Mean age was 35.1 years (95% CI ±2.0). Gender distribution was approximately equal (51.3% male). The Mean Harvey Bradshaw and Simple Clinical Colitis Activity indices were 2.25 (95% CI ±0.40) and 1.64 (95% CI ±0.49). Mean Godin score difference before and after IBD diagnosis was 6.94 (p = 0.002). Patients with UC (41.8%) were more likely than patients with CD (23.0%) to reduce their exercise levels (p=0.04). FACIT scores were lower in patients who had experienced relapses (p=0.012) and had severe disease (p=0.011). Approximately 1/3 of patients had a reduction in their activity level post-IBD diagnosis. Conclusions Patients were significantly less physically active after a diagnosis of IBD and this was more apparent in UC. Identification of risk factors associated with loss of fitness levels would help address the reduced patients` quality of life.

Cutaneous ultrasound biomicroscopy using a 50 MHz transducer is a useful tool for the following applications: (i) to identify the skin layers (including the epidermis, dermis and subcutaneous fat); (ii) to demonstrate the hair follicles in various areas of the haired skin; and (iii) to measure the thickness of normal canine skin accurately.

Background: Tocilizumab treatment is investigated, and effectiveness in ICU-admitted COVID-19 patients has been reported. Although controversy exists regarding the efficacy of tocilizumab treatment, it has been suggested that tocilizumab might show positive results depending on patient severity status. We examined an association between tocilizumab and distinct disease severity stages. Methods and Findings: From March 3 to March 23 2020, 494 consecutively admitted COVID-19 patients received tocilizumab or standard treatment alone. Data were obtained retrospectively. Clinical respiratory severity (CRS) stages were defined by patient oxygenation status and were also associated to scores of WHO clinical progression scale. We categorized patients in three stages, mild/moderate CRS1 (FiSpO2<0.35; WHO score 5), moderate/severe CRS2 (FiO2=0.5/high flow mask; WHO score 6) and severe/critical CRS3 (FiO2<80%/high flow/prone position or mechanical ventilation; score>6). The primary outcome was the composite of death or ICU admission in patients of stages CRS1, CRS2, and CRS3, as well as in total patients. We also addressed mortality alone in total patients. Kaplan-Maier curves, Cox proportional regression and inverse probability weighting marginal structural models were used. We conducted the study from March 3 to April 7 2020 with broad-ranged severity patients; 167 tocilizumab-treated and 327 untreated. CRS1 patients showed no apparent benefit after treatment, while the risk of the primary outcome was greatly reduced in CRS2 treated participants ((HR=0.22; 95% CI (0.16-0.44)). Moreover, tocilizumab treatment was associated with significantly decreased CRS2 patient proportion that reached the outcome compared to non-treated controls (27.8.0% vs. 65.4%; p<0.001). Severe/critical CRS3 patients, also showed benefit after treatment (HR=0.38; 95% CI (0.16-90)), although not as robust as was that of CRS2 treated individuals. Tocilizumab was associated with reduced outcome risk in total patients (HR=0.42; 95% CI (0.26-0.66)) after CRS adjustment, but not if CRS classification was not accounted as confounding factor (HR=1.19; 95% CI (0.84-1.69)). The outcome of mortality alone upon tocilizumab treatment was significant (HR=0.58; 95% CI (0.35-0.96)) after accounting for CRS classification. Conclusions: Tocilizumab treatment is associated with reduced COVID-19 escalation in CRS2 patients, suggesting efficacy in moderate/severe non-ICU-admitted patients. CRS classification could represent an essential confounding factor in evaluating tocilizumab in studies of broad-ranged severity patients.

The study aimed to monitor the healing process in the canine skin following surgical incision and closure using staples or tissue glue and to compare them with the intradermal suture pattern. Surgically created skin incisions in 10 dogs were apposed with staples, tissue glue (n-butyl cyanoacrylate) and continuous intradermal pattern. The cosmetic appearance of the wounds was blindly evaluated on days 7, 14 and 28 and once a month until the end of the experiment, i.e., one year after the incision. Ultrasonographic and clinical evaluation was performed on days 0–10, 12, 14, 16, 18, 21, 24 and 28, once a week until the end of the 3rd month and once a month until the end of the experiment. Histopathological evaluation was performed on days 7, 14, 28, 180 and 365. The median time required for the performance of each technique differed significantly between techniques; stapling lasted 21 seconds, glue 2 minutes 16 seconds and intradermal 15 minutes 37 seconds. Cosmetic appearance with glue was statistically worse than staples and intradermal. The clinical appearance of intradermal was significantly better than glue and staples. No significant differences were found at histological evaluation; however, glue had the worst score throughout the experiment. The overall evaluation of the techniques showed that glue had the worst score compared to intradermal and staples, with the difference being statistically significant in the first postoperative week. Intradermal suture pattern is much better than glue application for skin closure in dogs, whilst is not significantly better than staples. Staples should be preferred when time is an important factor.

The study aimed to compare incisional wound healing with intradermal suture patterns performed with (a) absorbable suture with burying of the knots and (b) nonabsorbable suture anchored with clips. Ten dogs were included in the study. Surgically created skin incisions were apposed with continuous intradermal suture pattern with 4/0 poliglecaprone 25 with burying of the knots and continuous intradermal pattern with 4/0 polypropylene with clips. Cosmetic, clinical, ultrasonographic and histological scores were evaluated. The intradermal pattern with clips was easier to perform and required significantly less time to complete than the intradermal suture with burying of the knots. Cosmetic, clinical, ultrasonographic and histological evaluation scores did not differ significantly between the techniques. Irrespective of the technique used, the cosmetic, ultrasonographic, clinical and histological appearances of the incisions improved over time. In conclusion, polypropylene was found to be a safe and effective suture material for use with intradermal suture pattern with clips in dogs and to have an easy and quick application. However, in our sample, its earlier removal from wounds than poliglecaprone 25 was not found to be associated with a supposedly beneficial effect on wound healing and scar appearance. Both suture materials can be useful in intradermal suture techniques in dogs.

No abstract

Peripheral tolerance is essential for suppressing autoimmunity and depends on the regulation of T cell activation, proliferation and apoptosis. p21, known originally as a cell cycle inhibitor, is implicated in effector/memory T cell responses and is considered a suppressor of lupus-like autoimmunity. However, the mechanism by which p21 regulates T cell responses and autoimmunity remains unknown. We investigated these questions by studying T cells of C57BL/6 p21-/- and C57BL/6-lpr p21-/- mice. p21 regulated activation of repeatedly stimulated effector/memory T cells in a cell cycle-independent manner, but had no effect on naïve T cells. We identified a previously non-described role for p21, in controlling T cell activation via downstream MAPK and NF-κB pathways in the cytoplasm. Lack of p21 caused hyperactivation of ERK1/2 and NF-κB in reactivated T cells. Importantly, p21-deficiency led to increased IFNγ production due to an effect of p21 on the IL-12- and IL-18-dependent IFNγ induction. Stimulation of TCR-transgenic T cells with specific antigens in vivo confirmed that p21 is involved in effector/memory T cell activation. Lack of p21 dramatically increased the mild lupus symptoms of C57BL/6-lpr mice to full-blown disease and death in C57BL/6-lpr p21-/- mice. The mechanism by which p21 regulates disease severity was based on its control of T cell activation and IFNγ production. Analysis of these p21 functions might be of therapeutic value for Lupus.

Fas drives activated T cell apoptosis in vitro, but lymphadenopathy and lupus development in Fas-deficient (lpr) mice cannot be explained only on the basis of the lpr T cell apoptotic defect. Unexplained also remains the in vivo hyperproliferation of T cells in lpr mice, including CD4+, CD8+ and CD4-CD8-TCR+ cells. To date, the effect of lpr T cell-hyperproliferation in both lymphadenopathy and lupus autoimmunity is not known. We investigate this point by generating T cell-specific p21-trangenic -lpr mice. p21, a cell cycle inhibitor and a lupus-like autoimmunity suppressor, regulates the expansion of memory but not of naïve T cells. p21 overexpression in lpr T cells did not affect primary T cell responses, but profoundly diminished lpr T cell proliferation after secondary activation, without affecting the compromised apoptotic cell death of lpr T cells. Importantly, in vivo, p21 overexpression restrains lpr T cell memory expansion, and results in reduced autoantibody production, glomerulonephritis and lymphadenopathy in lpr mice. p21 overexpression did not affect T cell memory in wt mice, pointing to a specialized role for p21 in hyperproliferating T cells. Overall we conclude that lpr T cell hyperproliferation is essential for the increased T cell memory, the autoimmunity and the lymphadenopathy development in lpr mice. Thus, decreasing the hyperproliferation of pathogenic T cells may be of therapeutic value for both Lupus and the Autoimmune Lymphoproliferative Syndrome.