Changing Roots

The Ross operation is a surgical intervention in which a diseased aortic valve is replaced by the pulmonary valve of the same patient. A donor valve replaces the pulmonary valve. In this thesis, several key unanswered clinical questions are explored. Early mortality after the Ross operation is relatively high in neonates. However, neonates and infants who survive the early post-operative period show impressive improvement of left ventricular function, preservation of autograft valve function and freedom from reoperation. Surgeons nowadays attempt to perform a valve-sparing reoperation in adult patients who require reoperation after the Ross operation for autograft root dilatation and/or valve insufficiency. This approach is associated with low morbidity and mortality. However, a large proportion of patients with isolated autograft valve insufficiency require a reintervention within the first two post-operative years. Histological and biomechanical analysis of explanted autograft valves and vessel wall has led to increased insight into remodelling after the Ross operation. Explanted autograft valves show a phenotype which is distinct from both native pulmonary and aortic valves. The explanted autograft shows a decrease in wall stiffness compared to the native pulmonary artery and aorta

Clinical relevance of endoscopic peri-appendiceal red patch in ulcerative colitis patients.

Background Increasing evidence is suggesting appendectomy as an alternative treatment for ulcerative colitis (UC), especially in case of histological appendiceal inflammation. Therefore, preoperative identification of appendiceal inflammation could be beneficial. This study aimed to assess the prevalence of peri-appendiceal red patch (PARP) on colonoscopy. In addition, prognostic relevance of PARP for disease course and its predictive value for histological appendiceal inflammation in patients undergoing appendectomy was assessed. Methods UC patients undergoing colonoscopy in 2014/2015 were included to determine PARP-prevalence in a cross-sectional study. Findings were correlated to patient and disease characteristics, upscaling of treatment and colectomy rates after cross-sectional colonoscopy. In patients undergoing appendiceal resection, histopathological inflammation was assessed using the Robarts Histopathology Index (RHI). Results In total, 249 patients were included of which 17.7% (44/249) had a PARP. Patients with PARP were significantly younger with a shorter disease course. The majority of patients with PARP (61.4%) was in endoscopic remission. Patients with PARP required more upscaling of medical therapy (81.8% vs. 58.0%, p < 0.01), and more PARP patients underwent colectomy (13.6% vs. 4.9%, p = 0.04). Patients with PARP had a higher median RHI in resection specimens (14 vs. 7, p < 0.01). Conclusion PARP was present during colonoscopy regardless disease activity and was predominantly found in UC patients with younger age and shorter disease duration. PARP patients had a more severe course of UC, and in case of appendectomy, more severe histopathological appendiceal inflammation. Appendectomy as an experimental therapy for UC has been suggested to be predominantly effective in UC patients with appendiceal inflammation. This study demonstrates that presence of a PARP on colonoscopy predicts appendiceal inflammation. After consensus has been reached on the therapeutic effect of appendectomy, assessing PARP presence during colonoscopy could therefore contribute to identifying patients most likely to respond

Prognostic Value of Colonic Tissue and Blood Eosinophils in Ulcerative Colitis.

BACKGROUND It has been suggested that eosinophils may be a prognostic marker of disease outcome in ulcerative colitis (UC), but conflicting data exist. The objective was to investigate the extent of mucosal eosinophils and peripheral blood eosinophil count in newly diagnosed UC patients and to investigate its predictive value in short- and long-term disease outcomes. METHODS The degree of eosinophilia in baseline colonic biopsies and blood of newly diagnosed UC patients was retrospectively analyzed. It was investigated if tissue and blood eosinophilia could be a marker of a severe phenotype of UC, defined as the need for corticosteroids or immunomodulators in the first year or treatment with therapeutic monoclonal antibodies or colectomy during follow-up. Time to therapeutic monoclonal antibodies and time to colectomy were also evaluated as outcomes. RESULTS There were 103 UC patients (median age 26 years) included. Median tissue peak eosinophil count (PEC) was 70.0 and median peripheral blood eosinophil count was 0.3 × 109/L at diagnosis. Tissue PEC (r = -0.161, P = .104) and blood eosinophil count (r = 0.022, P = .877) were not correlated with the severity of histologic inflammation. Logistic regression analyses did not identify PEC and blood eosinophil count as predictors of more severe disease outcomes. Tissue PEC and peripheral blood eosinophil count did not predict the time the initiation of therapeutic monoclonal antibodies or colectomy. CONCLUSION Baseline tissue or peripheral blood eosinophils are not markers of disease activity and cannot be used as a predictor of severe disease outcomes in both adults and children with UC

Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments

The clinical relevance of an inflamed appendix in Crohn's disease.

BACKGROUND AND AIMS An appendectomy for appendiceal inflammation has been suggested to ameliorate the clinical course of patients with ulcerative colitis (UC). In contrast, for Crohn's disease (CD) an inverse association has been suggested with a higher incidence of CD and worse prognosis after appendectomy. The aim of this study was to analyse the clinical relevance of an inflamed appendix in CD patients undergoing ileocoecal resection (ICR). METHODS All consecutive patients undergoing primary ICR between 2007 and 2018 were considered for inclusion. Microscopic data of available appendiceal resection specimens (n=99) were revised by a dedicated IBD-pathologist and scored as inflamed or not inflamed. Eighteen patients had a previous appendectomy. Pathological findings were correlated with disease characteristics and recurrence rates (clinical, endoscopic and intervention-related). RESULTS In total, 117 patients were included: 77 (65.8%) females with a median age of 30 years [IQR 24 - 43] with a median follow up of 102 months [IQR 76-114]. Of patients without previous appendectomy (n=99), 39% had an inflamed appendix. No significant differences in disease characteristics (e.g. disease location, behaviour, time to surgery) or prognosis could be demonstrated between the two groups. In contrast, previous appendectomy (n=18) was associated with penetrating disease and numerically shorter disease duration at the time of resection. Furthermore, a trend was seen towards a stronger association with postoperative recurrence. CONCLUSION The current study could not confirm a different prognosis for CD patients with and without an inflamed appendix. In contrast, in patients with a previous appendectomy a trend was seen towards increased postoperative recurrence, which might be related to the higher incidence of penetrating disease

Totally biological composite aortic stentless valved conduit for aortic root replacement: 10-year experience

<p>Abstract</p> <p>Objectives</p> <p>To retrospectively analyze the clinical outcome of a totally biological composite stentless aortic valved conduit (No-React^®BioConduit) implanted using the Bentall procedure over ten years in a single centre.</p> <p>Methods</p> <p>Between 27/10/99 and 19/01/08, the No-React^®BioConduit composite graft was implanted in 67 patients. Data on these patients were collected from the in-hospital database, from patient notes and from questionnaires. A cohort of patients had 2D-echocardiogram with an average of 4.3 ± 0.45 years post-operatively to evaluate valve function, calcification, and the diameter of the conduit.</p> <p>Results</p> <p>Implantation in 67 patients represented a follow-up of 371.3 patient-year. Males were 60% of the operated population, with a mean age of 67.9 ± 1.3 years (range 34.1-83.8 years), 21 of them below the age of 65. After a mean follow-up of 7.1 ± 0.3 years (range of 2.2-10.5 years), more than 50% of the survivors were in NYHA I/II and more than 60% of the survivors were angina-free (CCS 0). The overall 10-year survival following replacement of the aortic valve and root was 51%. During this period, 88% of patients were free from valved-conduit related complications leading to mortality. Post-operative echocardiography studies showed no evidence of stenosis, dilatation, calcification or thrombosis. Importantly, during the 10-year follow-up period no failures of the valved conduit were reported, suggesting that the tissue of the conduit does not structurally change (histology of one explant showed normal cusp and conduit).</p> <p>Conclusions</p> <p>The No-React^®BioConduit composite stentless aortic valved conduit provides excellent long-term clinical results for aortic root replacement with few prosthesis-related complications in the first post-operative decade.</p

Response to neoadjuvant chemotherapy and survival in molecular subtypes of resectable gastric cancer: : a post hoc analysis of the D1/D2 and CRITICS trials

Background Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment. Methods EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival. Results In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype. Conclusions In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.Surgical oncolog

Contextual effects on perceived contrast: Figure-ground assignment and orientation contrast

Figure-ground segregation is an important step in the path leading to object recognition. The visual system segregates objects ('figures') in the visual scene from their backgrounds ('ground'). Electrophysiological studies in awake-behaving monkeys have demonstrated that neurons in early visual areas increase their firing rate when responding to a figure compared to responding to the background. We hypothesized that similar changes in neural firing would take place in early visual areas of the human visual system, leading to changes in the perception of low-level visual features. In this study, we investigated whether contrast perception is affected by figure-ground assignment using stimuli similar to those in the electrophysiological studies in monkeys. We measured contrast discrimination thresholds and perceived contrast for Gabor probes placed on figures or the background and found that the perceived contrast of the probe was increased when it was placed on a figure. Furthermore, we tested how this effect compared with the well-known effect of orientation contrast on perceived contrast. We found that figure-ground assignment and orientation contrast produced changes in perceived contrast of a similar magnitude, and that they interacted. Our results demonstrate that figure-ground assignment influences perceived contrast, consistent with an effect of figure-ground assignment on activity in early visual areas of the human visual system

Pulmonary autograft valve explants show typical degeneration

Objectives: We sought to evaluate the microscopic characteristics of pulmonary autograft valve explants. Methods: Cell density and thickness of the autograft valve ventricularis were determined and compared with those of normal aortic and pulmonary valves (n = 11). Cellular phenotype and extracellular matrix involvement were assessed with immunohistochemistry. Collagen 3-dimensional architecture was studied by means of confocal microscopy. Results: The autograft valve exhibited characteristic thickening of the ventricularis compared with the normal aortic and pulmonary valves (137 vs 77 [P = .058] vs 37 mu m [P. = 002], respectively). Its cell number was increased compared with those of the normal aortic and pulmonary valves (396 vs 230 [P = .02] vs 303 [P = .083], respectively). Myofibroblasts and stressed endothelial cells, both of which were present in pulmonary autografts, were absent in control valves. The exclusive presence of matrix metalloproteinase 1 was an additional sign of extracellular matrix turnover. Apoptosis, elastinolysis, cell proliferation, and senescence were not expressed. Dense fibrosis of the autograft ventricularis with relatively well-aligned collagen fibers was observed with confocal microscopy. Conclusions: Fibrous hyperplasia of the ventricularis and cellular and extracellular matrix characteristics of active remodeling were a consistent finding in pulmonary autograft valve explants. The observations suggest a primary valve-related cause to be involved in pulmonary autograft valve failure. (J Thorac Cardiovasc Surg 2010;139:1416-9