Carbon Monoxide-Releasing Micelles for Immunotherapy

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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

Health status and psychological outcomes after trauma: A prospective multicenter cohort study

Introduction Survival after trauma has considerably improved. This warrants research on non-fatal outcome. We aimed to identify characteristics associated with both short and long-term health status (HS) after trauma and to describe the recovery patterns of HS and psychological outcomes during 24 months of follow-up. Methods Hospitalized patients with all types of injuries were included. Data were collected at 1 week 1, 3, 6, 12, and 24 months post-trauma. HS was assessed with the EuroQol-5D-3L (EQ-5D3L) and the Health Utilities Index Mark 2 and 3 (HUI2/3). For the screening of symptoms of post-traumatic stress, anxiety and depression, the Impact of Event Scale (IES) and the Hospital Anxiety and Depression Scale (HADS) subscale anxiety (HADSA) and subscale depression (HADSD) were used. Recovery patterns of HS and psychological outcomes were examined with linear mixed model analyses. Results A total of 4,883 patients participated (median age 68 (Interquartile range 53–80); 50% response rate). The mean (Standard Deviation (SD)) pre-injury EQ-5D-3L score was 0.85 (0.23). One week post-trauma, mean (SD) EQ-5D-3L, HUI2 and HUI3 scores were 0.49 (0.32), 0.61 (0.22) and 0.38 (0.31), respectively. These scores significantly improved to 0.77 (0.26), 0.77 (0.21) and 0.62 (0.35), respectively, at 24 months. Most recovery occurred up until 3 months. At long-term follow-up, patients of higher age, with comorbidities, longer hospital stay, lower extremity fracture and spine injury showed lower HS. The mean (SD) scores of the IES, HADSA and HADSD were respectively 14.80 (15.80), 4.92 (3.98) and 5.00 (4.28), respectively, at 1 week post-trauma and slightly improved over 24 months post-trauma to 10.35 (14.72), 4.31 (3.76) and 3.62 (3.87), respectively. Discussion HS and psychological symptoms improved over time and most improvements occurred within 3 months post-trauma. The effects of severity and type of injury faded out over time. Patients frequently reported symptoms of post-traumatic stress. Trial registration ClinicalTrials.gov identifier: NCT02508675

Impact of Splenic Artery Embolization on the Success Rate of Nonoperative Management for Blunt Splenic Injury

Introduction Nonoperative management (NOM) has become the treatment of choice for hemodynamically stable patients with blunt splenic injury. Results of outcome after NOM are predominantly based on large-volume studies from level 1 trauma centers in the United States. This study was designed to assess the results of NOM in a relatively low-volume Dutch level 1 trauma center. Methods An analysis of a prospective trauma registry was performed for a 6-year period before (period 1) and after the introduction and implementation of splenic artery embolization (SAE) (period 2). Primary outcome was the failure rate of initial treatment. Results A total of 151 patients were reviewed. An increased use of SAE and a reduction of splenic operations during the second period was observed. Compared with period 1, the failure rate after observation in period 2 decreased from 25% to 10%. The failure rate after SAE in period 2 was 18%. The splenic salvage rate (SSR) after observation increased from 79% in the first period to 100% in the second period. During the second period, all patients with failure after observation were successfully treated with SAE. The SSR after SAE in periods 1 and 2 was respectively 100% and 86%. Conclusions SAE of patients with blunt splenic injuries is associated with a reduction in splenic operations. The failure and splenic salvage rates in this current study were comparable with the results from large-volume studies of level 1 trauma centers. Nonoperative management also is feasible in a relatively low-volume level 1 trauma center outside the United State

Engineering integrin signaling for promoting embryonic stem cell self-renewal in a precisely defined niche

We present development and use of a 3D synthetic extracellular matrix (ECM) analog with integrin- specific adhesion ligands to characterize the microenvironmental influences in embryonic stem cell (ESC) self-renewal. Transcriptional analysis of 24 integrin subunits followed by confirmation at the trans- lational and functional levels suggested that integrins a5b1, avb5, a6b1 and a9b1 play important roles in maintenance of stemness in undifferentiated mouse ESCs. Using the well-defined matrix as a tool to activate integrins a5b1 plus avb5, a6b1 and a9b1, individually and in combination, differential integrin activation was demonstrated to exert exquisite control over ESC fate decisions. Simultaneous ligation of these four integrin heterodimers promoted self-renewal, as evidence by prolonged SSEA-1, Oct4 and Nanog expression, and induced Akt1 kinase signaling along with translational regulation of other stemness-related genes. The biofunctional network we have designed based on this knowledge may be useful as a defined niche for regulating ESC pluripotency through selective cell–matrix interactions, and the method we present may be more generally useful for probing matrix interactions in stem cell self- renewal and differentiation

Efficiency of stress-adaptive traits chlorophyll fluorescence and membrane thermo- stability in wheat under high temperature

Despite developments in targeted gene sequencing and whole-genome analysis techniques, the robust detection of all genetic variation, including structural variants, in and around genes of interest and in an allele-specific manner remains a challenge. Here we present targeted locus amplification (TLA), a strategy to selectively amplify and sequence entire genes on the basis of the crosslinking of physically proximal sequences. We show that, unlike other targeted re-sequencing methods, TLA works without detailed prior locus information, as one or a few primer pairs are sufficient for sequencing tens to hundreds of kilobases of surrounding DNA. This enables robust detection of single nucleotide variants, structural variants and gene fusions in clinically relevant genes, including BRCA1 and BRCA2, and enables haplotyping. We show that TLA can also be used to uncover insertion sites and sequences of integrated transgenes and viruses. TLA therefore promises to be a useful method in genetic research and diagnostics when comprehensive or allele-specific genetic information is needed

Recurrent differentiated thyroid cancer: Towards personalized treatment based on evaluation of tumor characteristics with PET (THYROPET Study): Study protocol of a multicenter observational cohort study

Background: After initial treatment of differentiated thyroid carcinoma (DTC) patients are followed with thyroglobulin (Tg) measurements to detect recurrences. In case of elevated levels of Tg and negative neck ultrasonography, patients are treated 'blindly' with Iodine-131 (131I). However, in up to 50% of patients, the post-therapy scan reveals no 131I-targeting of tumor lesions. Such patients derive no benefit from the blind therapy but are exposed to its toxicity. Alternatively, iodine-124 (124I) Positron Emission Tomography/Computed Tomography (PET/CT) has become available to visualize DTC lesions and without toxicity. In addition to this, 18F-fluorodeoxyglucose (18F-FDG) PET/CT detects the recurrent DTC phenotype, which lost the capacity to accumulate iodine. Taken together, the combination of 124I and 18F-FDG PET/CT has potential to stratify patients for treatment with 131I.Methods/Design: In a multicenter prospective observational cohort study the hypothesis that the combination of 124I and 18F-FDG PET/CT can avoid futile 131I treatments in patients planned for 'blind' therapy with 131I, is tested.One hundred patients planned for 131I undergo both 124I and 18F-FDG PET/CT after rhTSH stimulation. Independent of the outcome of the scans, all patients will subsequently receive, after thyroid hormone withdrawal, the 131I therapy. The post 131I therapeutic scintigraphy is compared with the outcome of the 124I and 18F-FDG PET/CT in order to evaluate the diagnostic value of the combined PET modalities.This study primary aims to reduce the number of futile 131I therapies. Secondary aims are the nationwide introduction of 124I PET/CT by a quality assurance and quality control (QA/QC) program, to correlate imaging outcome with histopathological features, to compare 124I PET/CT after rhTSH and after withdrawal of thyroid hormone, and to compare 124I and 131I dosimetry.Discussion: This study aims to evaluate the potential value of the combination of 124I and 18F-FDG PET/CT in the prevention of futile 131I therapies in patients with biochemically suspected recurrence of DTC. To our best knowledge no studies addressed this in a prospective cohort of patients. This is of great clinical importance as a futile 131I is a costly treatment associated with morbidity and therefore should be restricted to those likely to benefit from this treatment.Trial registration: Clinicaltrials.gov identifier: NCT01641679

Vuurwerkletsel in Zuidwest-Nederland rond de jaarwisseling 2017-2018

OBJECTIVE: To report the number of patients with firework-related injuries treated in December 2017 and January 2018 in a hospital in the south-west Netherlands trauma region, and to provide details about the types of firework used and the specific injuries. DESIGN: A prospective multicentre cohort study (NTR6793). METHODS: Patients of all ages with firework-related injuries were eligible for inclusion. The injury had to have been sustained between 1 December 2017 and 31 January 2018, and treated at a hospital in the south-west Netherlands trauma region (approximately 2.5 million inhabitants). Data were extracted from patients' medical files and additional information was obtained from patient interviews. RESULTS: Fifty-four patients were included. The majority were male (93%) and the median age was 15 years. Twenty-five (46%) patients were bystanders and 12 (22%) were injured by illegal fireworks. Fifty patients were injured by bangers (n=22) or decorative fireworks (n=28). The patients had a total of 79 injuries, of which 29 (37%) were localised to the upper extremity and 19 (24%) to the eyes. Most upper extremity injuries were burns (69%), primarily partial thickness. Of the eye injuries, 14 were caused by blunt trauma, seven by chemical trauma, and one by penetrating trauma. Three patients sustained indirect firework-related injuries. CONCLUSION: Between 1 December 2017 and 31 January 2018 in the south-west Netherlands trauma region mainly teenage males and bystanders sustained firework-related injuries. Most injuries were upper extremity burns and eye injuries, mainly due to legal fireworks and bangers or decorative fireworks. The extent of the sample indicatDoel Een volledig overzicht geven van het aantal vuurwerkslachtoffers dat in december 2017 en januari 2018 behandeld werd in een ziekenhuis in de traumaregio Zuidwest-Nederland, het gebruikte soort vuurwerk en de specifieke letsels. Opzet Een prospectieve, multicentrische cohortstudie (NTR6793). Methode Patiënten van alle leeftijden met vuurwerkletsel kwamen in aanmerking voor inclusie. Het letsel moest zijn ontstaan in de periode 1 december 2017-31 januari 2018 en zijn behandeld in een ziekenhuis in de traumaregio Zuidwest-Nederland (circa 2,5 miljoen inwoners). Gegevens werden verzameld vanuit het patiëntendossier en aanvullende gegevens werden verkregen tijdens een interview. Resultaten Er werden 54 patiënten geïncludeerd. Het overgrote deel betrof mannen (93%) en de mediane leeftijd was 15 jaar. 25 gewonden (46%) waren omstander en 12 mensen (22%) raakten gewond door illegaal vuurwerk. Van de 54 patiënten raakten er 50 gewond door knalvuurwerk (n = 22) of siervuurwerk (n = 28). De 54 geïncludeerde patiënten hadden 79 letsels; het letsel was 29 keer (37%) gelokaliseerd aan armen of handen en 19 keer (24%) aan de ogen. Letsel aan de arm of hand bestond voornamelijk uit brandwonden (69%), met name tweedegraads. Oogletsel werd 14 keer door stomp inwerkend geweld veroorzaakt, 7 keer door chemisch letsel en 1 keer werd het oog gepenetreerd. Er raakten 3 patiënten indirect gewond door vuurwerk. Conclusie In de traumaregio Zuidwest-Nederland raakten in de 2 maanden rond de jaarwisseling 2017-2018 vooral minderjarige mannen en omstanders gewond. Slachtoffers liepen met name brandwonden aan armen of handen of oogletsel op. De verwondingen waren met name het gevolg van legaal knal- en siervuurwerk. Door de omvang van de steekproef lijken de studiebevindingen goed te extrapoleren naar het gehele land