New records of Laboulbeniales (Fungi, Ascomycota) for The Netherlands

Laboulbeniales are obligate ectoparasitic ascomycetes occurring on Arthropoda, mostly insects. Since the 1950s almost no research on Laboulbeniales has been done in The Netherlands. This study presents a preliminary list of Laboulbeniales found on insects collected in De Kaaistoep. Thirteen species of Laboulbeniales were found on fourteen different insect hosts, nine of which are new to The Netherlands. One dipteran host is new to the entomofauna of The Netherlands

A biomechanical mathematical model for the collagen bundle distribution-dependent contraction and subsequent retraction of healing dermal wounds

A continuum hypothesis-based, biomechanical model is presented for the simulation of the collagen bundle distribution-dependent contraction and subsequent retraction of healing dermal wounds that cover a large surface area. Since wound contraction mainly takes place in the dermal layer of the skin, solely a portion of this layer is included explicitly into the model. This portion of dermal layer is modeled as a heterogeneous, orthotropic continuous solid with bulk mechanical properties that are locally dependent on both the local concentration and the local geometrical arrangement of the collagen bundles. With respect to the dynamic regulation of the geometrical arrangement of the collagen bundles, it is assumed that a portion of the collagen molecules are deposited and reoriented in the direction of movement of (myo)fibroblasts. The remainder of the newly secreted collagen molecules are deposited by ratio in the direction of the present collagen bundles. Simulation results show that the distribution of the collagen bundles influences the evolution over time of both the shape of the wounded area and the degree of overall contraction of the wounded area. Interestingly, these effects are solely a consequence of alterations in the initial overall distribution of the collagen bundles, and not a consequence of alterations in the evolution over time of the different cell densities and concentrations of the modeled constituents. In accordance with experimental observations, simulation results show furthermore that ultimately the majority of the collagen molecules ends up permanently oriented toward the center of the wound and in the plane that runs parallel to the surface of the skin

Stromal vascular fraction-enriched fat grafting as treatment of adherent scars:study design of a non-randomized early phase trial

BACKGROUND: In the last decades, autologous fat grafting has been used to treat adherent dermal scars. The observed regenerative and scar-reducing properties have been mainly ascribed to the tissue-derived stromal vascular fraction (tSVF) in adipose tissue. Adipose tissue's components augment local angiogenesis and mitosis in resident tissue cells. Moreover, it promotes collagen remodeling. We hypothesize that tSVF potentiates fat grafting-based treatment of adherent scars. Therefore, this study aims to investigate the effect of tSVF-enriched fat grafting on scar pliability over a 12-month period.METHODS AND DESIGN: A clinical multicenter non-randomized early phase trial will be conducted in two dedicated Dutch Burn Centers (Red Cross Hospital, Beverwijk, and Martini Hospital, Groningen). After informed consent, 46 patients (≥18 years) with adherent scars caused by burns, necrotic fasciitis, or degloving injury who have an indication for fat grafting will receive a sub-cicatricic tSVF-enriched fat graft. The primary outcome is the change in scar pliability measured by the Cutometer between pre- and 12 months post-grafting. Secondary outcomes are scar pliability (after 3 months), scar erythema, and melanin measured by the DSM II Colormeter; scar quality assessed by the patient and observer scales of the Patient and Observer Scar Assessment Scale (POSAS) 2.0; and histological analysis of scar biopsies (voluntary) and tSVF quality and composition. This study has been approved by the Dutch Central Committee for Clinical Research (CCMO), NL72094.000.20.CONCLUSION: This study will test the clinical efficacy of tSVF-enriched fat grafting to treat dermal scars while the underlying working mechanism will be probed into too.TRIAL REGISTRATION: Dutch Trial Register NL 8461. Registered on 16 March 2020.</p

The effect of TGFβRI inhibition on fibroblast heterogeneity in hypertrophic scar 2D in vitro models.

In burn patients, wound healing is often accompanied by hypertrophic scarring (HTS), resulting in both functional and aesthetic problems. HTSs are characterized by abundant presence of myofibroblasts (MFs) residing in the dermis. HTS development and MF persistence is primarily regulated by TGF-β signalling. A promising method to target the transforming growth factor receptor I (TGFβRI; also known as activin-like kinase 5 (ALK5)) is by making use of exon skipping through antisense oligonucleotides. In HTS the distinguishing border between the papillary dermis and the reticular dermis is completely abrogated, thus exhibiting a one layered dermis containing a heterogenous fibroblast population, consisting of papillary fibroblasts (PFs), reticular fibroblasts (RFs) and MFs. It has been proposed that PFs, as opposed to RFs, exhibit anti-fibrotic properties. Currently, it is still unclear which fibroblast subtype is most affected by exon skipping treatment. Therefore, the aim of this study was to investigate the effect of TGFβRI inhibition by exon skipping in PF, RF and HTS fibroblast monocultures. Morphological analyses revealed the presence of a PF-like population after exon skipping in the different fibroblast cultures. This observation was further confirmed by the expression of genes specific for PFs, demonstrated by qPCR analyses. Further investigations on mRNA and protein level revealed that indeed MFs and to a lesser extent RFs are targeted by exon skipping. Furthermore, collagen gel contraction analysis showed that ALK5 exon skipping reduced TGF-β- induced contraction together with decreased alpha-smooth muscle actin expression levels. In conclusion, we show for the first time that exon skipping primarily targets pro-fibrotic fibroblasts. This could be a promising step towards reduced HTS development of burn tissue

The Role of Burn Centers in the Treatment of Necrotizing Soft-Tissue Infections:A Nationwide Dutch Study

Patients with extensive and complex wounds due to Necrotizing Soft-Tissue Infections (NSTI) may be referred to a burn center. This study describes the characteristics, outcomes, as well as diagnostic challenges of these patients. Patients admitted to three hospitals with a burn center for the treatment of NSTI in a 5-year period were included. Eighty patients (median age 54 years, 60% male) were identified, of whom 30 (38%) were referred by other centers, usually after survival of the initial septic phase. Those referred from other centers, compared to those primarily admitted to the study hospitals, were more likely to have group A streptococcal involvement (62% vs 35%, p = .02), larger wounds (median 7% vs 2% total body surface area, p &lt; .001), and a longer length of stay (median 49 vs 22 days, p &lt; .001). Despite a high incidence of septic shock (50%), the mortality rate was low (12%) for those primarily admitted. Approximately half (53%) of the patients were initially misdiagnosed upon presentation, which was associated with delay to first surgery (16 hours vs 4 hours, p &lt; .001). Those initially misdiagnosed had more (severe) comorbidities, and less frequently reported pain or blue livid discoloration of the skin. This study underlines the burn centers' function as referral centers for extensively affected patients with NSTI. Besides the unique wound and reconstructive expertise, the low mortality rate indicates these centers provide adequate acute care as well. A major remaining challenge remains recognition of the disease upon presentation. Future studies in which factors associated with misdiagnosis are explored are needed.</p

Hydrosurgical and conventional debridement of burns:randomized clinical trial

Background: Tangential excision of burned tissue followed by skin grafting is the cornerstone of burn surgery. Hydrosurgery has become popular for tangential excision, with the hypothesis that enhanced preservation of vital dermal tissue reduces scarring. The aim of this trial was to compare scar quality after hydrosurgical versus conventional debridement before split-skin grafting. Methods: A double-blind randomized within-patient multicentre controlled trial was conducted in patients with burns that required split-skin grafting. One wound area was randomized to hydrosurgical debridement and the other to Weck knife debridement. The primary outcome was scar quality at 12 months, assessed with the observer part of the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes included complications, scar quality, colour, pliability, and histological dermal preservation. Results: Some 137 patients were randomized. At 12 months, scars of the hydrosurgical debrided wounds had a lower POSAS observer total item score (mean 2.42 (95 per cent c.i. 2.26 to 2.59) versus 2.54 (95 per cent c.i. 2.36 to 2.72; P =0.023)) and overall opinion score (mean 3.08 (95 per cent c.i. 2.88 to 3.28) versus 3.30 (95 per cent c.i. 3.09-3.51); P = 0.006). Patient-reported scar quality and pliability measurements were significantly better for the hydrosurgically debrided wounds. Complication rates did not differ between both treatments. Histologically, significantly more dermis was preserved with hydrosurgery (P < 0.001). Conclusion: One year after surgery scar quality and pliability was better for hydrosurgically debrided burns, probably owing to enhanced histological preservation of dermis

Early Laser for Burn Scars (ELABS): protocol for a multi-centre randomised, controlled trial of both the effectiveness and cost-effectiveness of the treatment of hypertrophic burn scars with Pulsed Dye Laser and standard care compared to standard care alone [version 1; peer review: 2 approved].

This paper outlines the protocol for a study that is being carried out at multiple centres across the UK in the next three years. It is a Research for Patient Benefit (RfPB) study funded by the National Institute for Healthcare Research (NIHR). The aim is to assess the effectiveness of treating hypertrophic burns scars with pulsed dye laser (PDL) at an early stage of scar formation. The objective is to improve Quality of Life for the patient by improving both the appearance and quality of burn scarring, as well as reducing its psychological impact. This is a parallel-arm randomised, controlled trial to compare PDL and standard care against standard care alone. The difference is measured between baseline and six-month follow-up. Recruits are within three months of healing from a burn injury; with wounds showing a defined potential for hypertrophic scarring. A total of 120 patients are recruited in a multi-centre study; with randomisation in a 1:1 allocation to each arm. The treatment arm receives 3 PDL treatments at six-week intervals in addition to standard care, whereas the control arm receives standard care alone. The primary outcome is the patient-rated part of the Patient and Observer Scar Scale (POSAS). Psychological and psycho-social impact is evaluated using the CARe burn scale (UWE, Bristol) and Quality Adjusted Life Years (QALY) is determined using the Short-Form Health Survey (SF-12). The study evaluates both the cost-effectiveness through an economic analysis and the patient-reported experience of the treatment by phone interviews

Rasch analysis of the Patient and Observer Scar Assessment Scale (POSAS) in burn scars

The Patient and Observer Scar Assessment Scale (POSAS) is a questionnaire that was developed to assess scar quality. It consists of two separate six-item scales (Observer Scale and Patient Scale), both of which are scored on a 10-point rating scale. After many years of experience with this scale in burn scar assessment, it is appropriate to examine its psychometric properties using Rasch analysis. Cross-sectional data collection from seven clinical trials resulted in a data set of 1,629 observer scores and 1,427 patient scores of burn scars. We examined the person-item map, item fit statistics, reliability, response category ordering, and dimensionality of the POSAS. The POSAS showed an adequate fit to the Rasch model, except for the item surface area. Person reliability of the Observer Scale and Patient Scale was 0.82 and 0.77, respectively. Dimensionality analysis revealed that the unexplained variance by the first contrast of both scales was 1.7 units. Spearman correlation between the Observer Scale Rasch measure and the overall opinion of the clinician was 0.75. The Rasch model demonstrated that the POSAS is a reliable and valid scale that measures the single-construct scar qualit