Trauma-informed Approaches to Substance Use Interventions with Indigenous Peoples: A Scoping Review.

Indigenous Peoples experience disproportionately higher rates of problematic substance use. These problems are situated in a context of individual and intergenerational trauma from colonization, residential schools, and racist and discriminatory practices, policies, and services. Therefore, substance use interventions need to adopt a trauma-informed approach. We aimed to synthesize and report the current literature exploring the intersection of trauma and substance use interventions for Indigenous Peoples. Fourteen databases were searched using keywords for Indigenous Peoples, trauma, and substance use. Of the 1373 sources identified, 117 met inclusion criteria. Literature on trauma and substance use with Indigenous Peoples has increased in the last 5 years (2012-2016, n = 29; 2017-2021, n = 48), with most literature coming from the United States and Canada and focusing on historical or intergenerational trauma. Few articles focused on intersectional identities such as 2SLGBTQIA+ (n = 4), and none focused on veterans. There were limited sources (n = 25) that reported specific interventions at the intersection of trauma and substance use. These sources advocate for multi-faceted, trauma-informed, and culturally safe interventions for use with Indigenous Peoples. This scoping review illuminates gaps in the literature and highlights a need for research reporting on trauma-informed interventions for substance use with Indigenous Peoples.

Using encrusting bryozoan adhesion to evaluate the efficacy of fouling-release marine coatings.

Biofouling communities are spatiotemporally diverse, underscoring the need to assess fouling-release (FR) coating performance against common biofouling taxa at multiple field sites. Adhesion strength assessments of FR coatings incorporate few taxa into standardized protocols. This study tested the feasibility of incorporating existing ASTM barnacle protocols on tubeworms and encrusting bryozoans (EB). Additionally, trends in adhesion strength among these taxa were compared at two field sites. EB adhesion at both field sites showed consistent results and adhesion strength followed the same trend: tubeworms > barnacles >EB. Testing EB adhesion was feasible and enhanced assessments of FR coatings by increasing the diversity of assessed taxa.

Perfusion bioreactor-based cryopreservation of 3D human mesenchymal stromal cell tissue grafts.

The generation of an off-the-shelf in vitro engineered living tissue graft will likely require cryopreservation. However, the efficient addition and removal of cryoprotective agents (CPA) to cells throughout the volume of a three-dimensional (3D) tissue graft remains a significant challenge. In this work, we assessed whether a perfusion bioreactor-based method could be used to improve the viability of cryopreserved mesenchymal stromal cell- (MSC) based tissue constructs as compared to using conventional diffusion-based methods. The bioreactor was first used to saturate 3D constructs with CPA under perfused flow. Following cryopreservation, the bioreactor was then also used for the efficient removal of the CPA from the 3D tissues. We demonstrate that addition and removal of CPA under perfused flow significantly increased the viability of MSC within cryopreserved 3D tissue constructs as compared to conventional diffusion-based methods.

Streamlined bioreactor-based production of human cartilage tissues.

Engineered tissue grafts have been manufactured using methods based predominantly on traditional labour-intensive manual benchtop techniques. These methods impart significant regulatory and economic challenges, hindering the successful translation of engineered tissue products to the clinic. Alternatively, bioreactor-based production systems have the potential to overcome such limitations. In this work, we present an innovative manufacturing approach to engineer cartilage tissue within a single bioreactor system, starting from freshly isolated human primary chondrocytes, through the generation of cartilaginous tissue grafts. The limited number of primary chondrocytes that can be isolated from a small clinically-sized cartilage biopsy could be seeded and extensively expanded directly within a 3D scaffold in our perfusion bioreactor (5.4 ± 0.9 doublings in 2 weeks), bypassing conventional 2D expansion in flasks. Chondrocytes expanded in 3D scaffolds better maintained a chondrogenic phenotype than chondrocytes expanded on plastic flasks (collagen type II mRNA, 18-fold; Sox-9, 11-fold). After this "3D expansion" phase, bioreactor culture conditions were changed to subsequently support chondrogenic differentiation for two weeks. Engineered tissues based on 3D-expanded chondrocytes were more cartilaginous than tissues generated from chondrocytes previously expanded in flasks. We then demonstrated that this streamlined bioreactor-based process could be adapted to effectively generate up-scaled cartilage grafts in a size with clinical relevance (50 mm diameter). Streamlined and robust tissue engineering processes, as the one described here, may be key for the future manufacturing of grafts for clinical applications, as they facilitate the establishment of compact and closed bioreactor-based production systems, with minimal automation requirements, lower operating costs, and increased compliance to regulatory guidelines.

Risk factors for bleeding complications after percutaneous dilatational tracheostomy: a ten-year institutional analysis.

Bleeding complications after percutaneous dilatational tracheostomy (PDT) are infrequent but may have a tremendous impact on a patient's further clinical course. Therefore, it seems necessary to perform risk stratification for patients scheduled for PDT. We retrospectively reviewed the records of 1001 patients (46% male, mean age 68.1 years) undergoing PDT (using the Ciaglia Blue Rhino® technique with direct bronchoscopic guidance) in our cardiothoracic ICU between January 2003 and February 2013. Patients were stratified into two groups: patients suffering acute moderate, severe, or major bleeding (Group A) and patients who had no or only mild bleeding (Group B). In the majority of patients, no or only mild bleeding during PDT occurred (none: 425 [42.5%], mild: 488 [48.8%]). In 84 patients (8.4%), bleeding was classified as moderate. Three patients suffered from severe bleeding; only one major bleed with need for emergency surgery occured. Patients in Group A had a significantly higher Simplified Acute Physiology Score on the day of PDT (P=0.042), higher prevalence of renal replacement therapy on the day of PDT (P=0.026), higher incidence of coagulopathy (P=0.043), lower platelet counts (P=0.037), lower fibrinogen levels (P=0.012), higher proportion of PDTs performed by residents (P=0.034) and higher difficulty grading of PDT (P=0.001). Using logistic regression analyses, difficult PDT, less experienced operator, Simplified Acute Physiology Score>40 and low fibrinogen levels were independent predictors of clinically significant bleeding after PDT. Low fibrinogen levels, as well as difficult PDT, less experienced operator and Simplified Acute Physiology Score>40 are associated with an increased risk for bleeding during PDT.

A novel calcium scoring system accurately predicts likelihood and location of post-TAVI paravalvular leak.

AIM: Sclerosis distribution, topography and morphology in aortic stenosis may have an impact on the localisation of post-procedural paravalvular leakage (PVL) following transcatheter aortic valve implantation (TAVI). METHODS: Between 05/2005 and 03/2011 a total of 208 patients underwent either transapical (TA) or transvascular (TV) TAVI using the Edwards-SAPIEN(TM), or CoreValve(TM) system. Aortic cusp and annular sclerosis distribution and aortic valve sclerosis symmetry were evaluated by preoperative transesophageal echocardiography (TOE). Mild, moderate and severe PVL after TAVI (group 1, N.=117) were analysed and compared to those patients with no signs of postprocedural PVL (group 2, N.=91). Commercial available image processing and analysing software were used to evaluate all relevant calcific sections (aortic sclerosis score 0-66; symmetry score 0-5) and were matched with the localization of the PVLs. RESULTS: A total of 117 patients (83±6 years, mean logistic EuroSCORE 20.1±12.7%) were identified with a mild-moderate PVL (TV, N.=102; TA, N.=15). Mean aortic sclerosis score was 38.7±7.6 in group 1 compared to 33.7±8.3 in group 2 (P<0.001) showing highest calcification in the non-coronary part for both groups. The mean symmetry score was 1.9±1.0 group 1 compared to 1.7±1.0 in group 2 (P=0.12). Regression analysis showed a significant relation of preoperative cusp localisation to the corresponding paravalvular leakage (P<0.001). CONCLUSION: The present study shows that a aortic sclerosis score constructed by TOE enables prediction of postoperative PVL and moreover, the localisation of PVL after TAVI correlates with the corresponding preoperative amount of sclerosis for each cusp.

Arrhythmogenic risk of pulmonary artery catheterisation in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation.

Many clinicians consider severe aortic stenosis to be a contraindication to pulmonary artery catheterisation, except during open heart surgery with cardiopulmonary bypass. This is due to the perceived high risk of arrhythmia, although the true incidence of ventricular tachycardia and fibrillation remains unclear. We conducted a retrospective study to estimate the incidence of severe arrhythmias during pulmonary artery catheterisation in 380 patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation. Ventricular fibrillation was seen in only one patient (0.26%), and this was successfully terminated by external defibrillation. No episodes of ventricular tachycardia were recorded and there were also no arrhythmias during removal of the catheter. We have therefore concluded that pulmonary artery catheterisation in patients with severe aortic stenosis is not associated with a high incidence of ventricular fibrillation or tachycardia, allowing pulmonary artery pressure monitoring to be performed relatively safely in such patients.

On-line monitoring of oxygen as a non-destructive method to quantify cells in engineered 3D tissue constructs.

Regulatory guidelines have established the importance of introducing quantitative quality controls during the production and/or at the time of release of cellular grafts for clinical applications. In this study we aimed to determine whether on-line measurements of oxygen can be used as a non-destructive method to estimate the number of chondrocytes within an engineered cartilage graft. Human chondrocytes were seeded and cultured in a perfusion bioreactor, and oxygen levels in the culture medium were continuously monitored at the inlet and outlet of the bioreactor chamber throughout the culture period. We found that the drop in oxygen across the perfused construct was linearly correlated with the number of cells per construct (R(2) = 0.82, p < 0.0001). The method was valid for a wide range of cell numbers, including cell densities currently used in the manufacture of cartilage grafts for clinical applications. Given that few or no non-destructive assays that quantitatively characterize an engineered construct currently exist, this non-invasive method could represent a relevant instrument in regulatory compliant manufacturing of engineered grafts meeting specific quality criteria.

[Angioscopy: a new intraoperative diagnostic and interventional tool for thoracic aortic treatment]. / Angioskopie: Neues intraoperatives diagnostisches und interventionelles Verfahren für die Therapie der thorakalen Aortenerkrankung.

In complex thoracic aortic disease endovascular techniques and the use of hybrid stent grafts enables a combination therapy of the aortic arch and the descending aorta through a median sternotomy. This emphasizes the importance of intraoperative visualization of the descending aorta and its pathologies. Intraoperative angioscopy is a new diagnostic method for the assessment of distal aortic disease and assists in therapeutic decision-making and navigation of endovascular techniques in the descending aorta. This study presents the angioscopic results of 62 patients (mean age 60±12 years, 73% male, 54 aortic dissections, eight aortic aneurysms) during surgery of the thoracic aorta. Visualization of the extent of pathology along the downstream aorta was feasible in all patients. The implantation of a hybrid stent graft prosthesis was assisted by angioscopy in 34 patients and endovascular balloon dilatation of the stent graft was navigated by angioscopy in 11 patients. Angioscopy has become an indispensable tool in the intraoperative treatment of complex thoracic aortic disease in our clinic, particularly in the navigation of endovascular interventions in the distal thoracic aorta through the aortic arch.

Current developments in transcatheter aortic valve implantation techniques.

Transcatheter aortic valve implantation (TAVI) has become a viable treatment option in high-risk patients with symptomatic aortic stenosis. The widespread uses of TAVI procedures in recent years and the steadily growing evolution of numerous new catheter-based devices have led to a remarkable shift in the treatment of this patients group towards TAVI procedures. Several developments have now overcome most of the initial problems with the early devices and have been quickly implemented in clinical routine. Nevertheless, several current TAVI systems have shown a number of limitations and disadvantages relating to valve design, the occurrence of paravalvular leakages, valve positioning and deployment, the occurrence of thromboembolic events during the procedure, as well as vascular or conduction complications. As a result, all current efforts in further development focus primarily on the following issues: (1) the further miniaturization of catheter devices and sheaths not only to facilitate transarterial but also transapical access; (2) the development of a broad variety of valve sizes to cover all aortic annulus sizes; (3) the development of retrievable, repositionable and removable systems; (4) the development or modification of stent design to prevent or reduce paravalvular leakages; (5) the implementation of modern imaging and navigation tools; (6) and finally, the initial development of prophylactic devices to prevent thromboembolic events. The present article provides a review of current developments in the field of TAVI.

Towards trends in minimal invasive cardiac surgery.

While various minimally invasive techniques have been established in many other surgical specialties during the last decades, cardiac surgery has been one of the last domains to adopt the principles of minimally invasive techniques. This was mainly based on the reduced surgical exposure in highly complex cardiac operations and the missing technical requirements in the beginning of the modern cardiac era. Nowadays, technical conditions have continuously improved and have become routine also in cardiac surgery. Most of these novel minimal-invasive concepts have been developed in order to treat high-risk or inoperable patients by reducing operative trauma. Actually, since more high-risk and multimorbid patients were referred for surgery, these initial extraordinary procedures have been adopted into daily clinical routine. Currently, many promising innovations aim to reduce the operative trauma and perioperative morbidity, and furthermore, to increase patients' satisfaction and security. It is anticipated that in the future this current trend towards minimal invasiveness will increase further due to an increased demand, and therefore, such minimal-invasive procedures will become less complex and straightforward.

Real-time measurements of human chondrocyte heat production during in vitro proliferation.

Isothermal microcalorimeters (IMC) are highly sensitive instruments that allow the measurement of heat flow in the microwatt range. Due to their detection of minute thermal heat, IMC techniques have been used in numerous biological applications, including the study of fermentation processes, pharmaceutical development, and cell metabolism. In this work, with the ultimate goal of establishing a rapid and real-time method to predict the proliferative capacity of human articular chondrocytes (HAC), we explored to use of IMC to characterize one of the crucial steps within the process of cartilage tissue engineering, namely the in vitro expansion of HAC. We first established an IMC-based model for the real-time monitoring of heat flow generated by HAC during proliferation. Profiles of the heat and heat flow curves obtained were consistent with those previously shown for other cell types. The average heat flow per HAC was determined to be 22.0 ± 5.3 pW. We next demonstrated that HAC proliferation within the IMC-based model was similar to proliferation under standard culture conditions, verifying its relevance for simulating the typical cell culture application. HAC growth and HAC heat over time appeared correlated for cells derived from particular donors. However, based on the results from 12 independent donors, no predictive correlation could be established between the growth rate and the heat increase rate of HAC. This was likely due to variability in the biological function of HAC derived from different donors, combined with the complexity of tightly couple metabolic processes beyond proliferation. In conclusion, IMC appears to be a promising technique to characterize cell proliferation. However, studies with more reproducible cell sources (e.g., cell lines) could be used before adding the complexity associated with primary human cells.

[Perioperative antocoagulation in patients with prosthetic heart valves: recommendations]. / Perioperatives Gerinnungsmanagement bei Patienten mit Kunstklappen : Empfehlungen.

Lifelong anticoagulation, mainly with oral Vitamin K antagonists, represents the treatment of choice in patients with prosthetic heart valves to prevent thrombembolic complications. As a result, anticoagulant-related complications like excessive bleeding during interventions or surgical procedures will occur. Therefore, timely stopping of vitamin K antagonists prior to elective surgery is mandatory. However, based on the long half-life of all common vitamin K antagonists, interruption of oral anticoagulation will definitively lead to an increase of thrombembolic events. Hence, adequate bridging anticoagulation by temporary substitution of this therapy with heparin is necessary. This article gives a recommendation on the basis of the American College of Chest Physician and European Society of Cardiology current.

Comparison of sequential left internal thoracic artery grafting and separate left internal thoracic artery and venous grafting : A 5-year follow-up.

OBJECTIVES: The superiority of left internal thoracic artery (LITA) grafting to the left anterior descending artery (LAD) is well established. Patency rates of 80%-90% have been reported at 10-year follow-up. However, the superiority of sequential LITA grafting has not been proven. Our aim was to compare patency rates after sequential LITA grafting to a diagonal branch and the LAD with patency rates of LITA grafting to the LAD and separate vein grafting to a diagonal branch. METHODS: A total of 58 coronary artery bypass graft (CABG) patients, operated on between 01/2000 and 12/2002, underwent multi-slice computed tomography (MSCT) between 2006 and 2008. Of these patients, 29 had undergone sequential LITA grafting to a diagonal branch and to the LAD ("Sequential" Group), while in 29 the LAD and a diagonal branch were separately grafted with LITA and vein ("Separate" Group). Patencies of all anastomoses were investigated. RESULTS: Mean follow-up was 1958±208 days. The patency rate of the LAD anastomosis was 100% in the Sequential Group and 93% in the Separate Group (p=0.04). The patency rate of the diagonal branch anastomosis was 100% in the Sequential Group and 89% in the Separate Group (p=0.04). Mean intraoperative flow on LITA graft was not different between groups (69±8ml/min in the Sequential Group and 68±9ml/min in the Separate Group, p=n.s.). CONCLUSION: Patency rates of both the LAD and the diagonal branch anastomoses were higher after sequential arterial grafting compared with separate arterial and venous grafting at 5-year follow-up. This indicates that, with regard to the antero-lateral wall of the left ventricle, there is an advantage to sequential arterial grafting compared with separate arterial and venous grafting.

Bioreactors in tissue engineering: scientific challenges and clinical perspectives.

In this Chapter we discuss the role of bioreactors in the translational paradigm of Tissue Engineering approaches from basic research to streamlined tissue manufacturing. In particular, we will highlight their functions as: (1) Pragmatic tools for tissue engineers, making up for limitations of conventional manual and static techniques, enabling automation and allowing physical conditioning of the developing tissues; (2) 3D culture model systems, enabling us to recapitulate specific aspects of the actual in vivo milieu and, when properly integrated with computational modeling efforts and sensing and control techniques, to address challenging scientific questions; (3) Tissue manufacturing devices, implementing bioprocesses so as to support safe, standardized, scaleable, traceable and possibly cost-effective production of grafts for clinical use. We will provide evidences that fundamental knowledge gained through the use of well-defined and controlled bio-reactor systems at the research level will be essential to define, optimize, and moreover, streamline the key processes required for efficient manufacturing models.

Cartilage tissue engineering using pre-aggregated human articular chondrocytes.

In this study, we first aimed at determining whether human articular chondrocytes (HAC) proliferate in aggregates in the presence of strong chondrocyte mitogens. We then investigated if the aggregated cells have an enhanced chondrogenic capacity as compared to cells cultured in monolayer. HAC from four donors were cultured in tissue culture dishes either untreated or coated with 1% agarose in the presence of TGFbeta-1, FGF-2 and PDGF-BB. Proliferation and stage of differentiation were assessed by measuring respectively DNA contents and type II collagen mRNA. Expanded cells were induced to differentiate in pellets or in Hyaff-11 meshes and the formed tissues were analysed biochemically for glycosaminoglycans (GAG) and DNA, and histologically by Safranin O staining. The amount of DNA in aggregate cultures increased significantly from day 2 to day 6 (by 3.2-fold), but did not further increase with additional culture time. Expression of type II collagen mRNA was about two orders of magnitude higher in aggregated HAC as compared to monolayer expanded cells. Pellets generated by aggregated HAC were generally more intensely stained for GAG than those generated by monolayer-expanded cells. Scaffolds seeded with aggregates accumulated more GAG (1.3-fold) than scaffolds seeded with monolayer expanded HAC. In conclusion, this study showed that HAC culture in aggregates does not support a relevant degree of expansion. However, aggregation of expanded HAC prior to loading into a porous scaffold enhances the quality of the resulting tissues and could thus be introduced as an intermediate culture phase in the manufacture of engineered cartilage grafts.

Computational evaluation of oxygen and shear stress distributions in 3D perfusion culture systems: macro-scale and micro-structured models.

We present a combined macro-scale/micro-scale computational approach to quantify oxygen transport and flow-mediated shear stress to human chondrocytes cultured in three-dimensional scaffolds in a perfusion bioreactor system. A macro-scale model was developed to assess the influence of the bioreactor design and to identify the proper boundary conditions for the micro-scale model. The micro-scale model based on a micro-computed tomography (microCT) reconstruction of a poly(ethylene glycol terephthalate)/poly(butylene terephthalate) (PEGT/PBT) foam scaffold, was developed to assess the influence of the scaffold micro-architecture on local shear stress and oxygen levels within the scaffold pores. Experiments were performed to derive specific oxygen consumption rates for constructs perfused under flow rates of 0.3 and 0.03 ml min(-1). While macro-scale and micro-scale models predicted similar average oxygen levels at different depths within the scaffold, microCT models revealed small local oxygen variations within the scaffold micro-architecture. The combined macro-scale/micro-scale approach indicated that 0.3 ml min(-1), which subjected 95% of the cells to less than 6.3 mPa shear, would maintain the oxygen supply throughout the scaffold above anoxic levels (>1%), with 99.5% of the scaffold supplied with 8-2% O(2). Alternatively, at 0.03 ml min(-1), the macro-scale model predicted 6% of the cells would be supplied with 0.5-1% O(2), although this region of cells was confined to the periphery of the scaffold. Together with local variations predicted by the micro-scale model, the simulations underline that in the current model system, reducing the flow below 0.03 ml min(-1) would likely have dire consequences on cell viability to pronounced regions within the engineered construct. The presented approach provides a sensitive tool to aid efficient bioreactor optimization and scaffold design.

Effects of fluid flow and calcium phosphate coating on human bone marrow stromal cells cultured in a defined 2D model system.

In this study, we investigated the effect of the long-term (10 days) application of a defined and uniform level of fluid flow (uniform shear stress of 1.2 x 10(-3) N/m(2)) on human bone marrow stromal cells (BMSC) cultured on different substrates (i.e., uncoated glass or calcium phosphate coated glass, Osteologictrade mark) in a 2D parallel plate model. Both exposure to flow and culture on Osteologic significantly reduced the number of cell doublings. BMSC cultured under flow were more intensely stained for collagen type I and by von Kossa for mineralized matrix. BMSC exposed to flow displayed an increased osteogenic commitment (i.e., higher mRNA expression of cbfa-1 and osterix), although phenotype changes in response to flow (i.e., mRNA expression of osteopontin, osteocalcin and bone sialoprotein) were dependent on the substrate used. These findings highlight the importance of the combination of physical forces and culture substrate to determine the functional state of differentiating osteoblastic cells. The results obtained using a simple and controlled 2D model system may help to interpret the long-term effects of BMSC culture under perfusion within 3D porous scaffolds, where multiple experimental variables cannot be easily studied independently, and shear stresses cannot be precisely computed.