Cellular and Molecular Mechanisms in Hypertrophic Scar Formation: Potential Targets for Therapy

Middelkoop, E. [Promotor]Molema, G. [Promotor]Niessen, F.B. [Copromotor

Nephrologists' perceptions regarding dialysis withdrawal and palliative care in Europe: lessons from a European Renal Best Practice survey

Background There is a variation in dialysis withdrawal rates, but reasons for this variation across European countries are largely unknown. We therefore surveyed nephrologists' perceptions of factors concerning dialysis withdrawal and palliative care and explored relationships between these perceptions and reports of whether withdrawal actually occurred in practice. Methods We developed a 33-item electronic survey, disseminated via an email blast to all European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) members. In our data analyses, we distinguished those respondents who reported occurrence from those reporting no dialysis withdrawal in their unit. With multilevel logistic regression, we investigated the association between respondents' characteristics and perceptions and whether they reported occurrence of dialysis withdrawal or not. Results Five hundred and twenty-eight nephrologists from 45 countries completed the questionnaire; 42% reported occurrence of withdrawal in their unit in the past year, and 56% perceived that stopping life-prolonging treatment in terminally ill patients was allowed. Few respondents reported presence in their unit of protocols on withdrawal decision making (7%) or palliative care (10%) or the common involvement of a geriatrician in withdrawal decisions (10%). The majority stated that palliative care had not been part of their core curriculum (74%) and that they had not recently attended continuous medical education sessions on this topic (73%). Respondents from Eastern and Southern Europe had a 42 and 40% lower probability, respectively, of reporting withdrawal compared with those from North European countries. Working in a public centre [odds ratio (OR), 2.41; 95% confidence interval (CI), 1.36-4.25] and respondents' perception that stopping life-prolonging treatment in terminally ill patients was allowed (OR, 1.96; 95% CI, 1.23-3.12), that withdrawal decisions were commonly shared between doctor and patient (OR, 1.97; 95% CI, 1.26-3.08) and that palliative care was reimbursed (OR, 1.81; 95% CI, 1.16-2.83) increased the odds of reporting occurrence of withdrawal. Conclusion Reports of dialysis withdrawal occurrence varied between European countries. Occurrence reports were more likely if respondents worked in a public centre, if stopping life-prolonging treatments was perceived as allowed, if withdrawal decisions were considered shared between doctors and patients and if reimbursement of palliative care was believed to be in place. There is room for improvement regarding protocols on withdrawal and palliative care processes and regarding nephrologists' training and education on end-of-life car

Perioperative conditions affect long-term hypertrophic scar formation

Corticosteroids are widely used as treatment for excessive scarring by intralesional injection with variable success rates. It is conceivable that systemically administered corticosteroids affect a wider range of inflammatory processes that influence wound healing and may be more successful in preventing hypertrophic scar formation. To study this presumption, we have used a standardized model of presternal scars caused by cardiothoracic surgery through a median sternotomy incision. During cardiac surgery with cardiopulmonary bypass, 1 mg/kg dexamethasone was administered preoperatively, and 0.5 mg/kg 8 hours postoperatively. The presternal scars were evaluated prospectively 2, 4, 6, 12, and 52 weeks postoperatively at standardized measuring points. The height and width of the scars were measured 12 and 52 weeks postoperatively using both a slide caliper and a 7.5-MHz ultrasound probe. Cardiopulmonary bypass was used in 31 of the 43 participants. Eleven patients (35%) in the dexamethasone group developed clinical hypertrophic scars compared with 4 patients (33%) in the control group. These differences were not statistically significant. However, cranial scars became significantly wider in the dexamethasone group compared with the control group (P = 0.04). Twelve weeks postoperatively scars were significantly higher in the dexamethasone group, both cranial (P = 0.05) and caudal (P = 0.03). The differences in scar width and height were mainly present in patients that developed hypertrophic scars. The present results suggest that administration of high-dose perioperative dexamethasone does not prevent hypertrophic scar formation. Its use together with the cardiopulmonary bypass, however, did affect scar dimensions negatively up to 52 weeks after surgery. These findings contribute to the concept of the involvement of perioperative immunologic responses in the etiology of hypertrophic scar formation