Biocompatible, porous hydrogels composed of aliphatic polyesters and poly(2-isopropenyl-2-oxazoline). Their application as scaffolds for bone tissue regeneration.

In this study, porous networks were efficiently prepared by crosslinking hydrophilic poly(2-isopropenyl-2-oxazoline) (PiPOx) with dicarboxylic polyesters (HOOC-PLA-COOH or HOOC-PCL-COOH) in the presence of sodium chloride as a water-soluble porogen. Importantly, by using a relatively simple synthetic protocol, the resulting spongy materials were freely formed to the desired size and shape while maintaining stable dimensions. According to the SEM data, the porous 3D structure can be altered by the pore dimensions, which are dependent on the porogen crystal size. After porosity characterization, the mechanical properties were also evaluated via uniaxial compression and tensile tests. The porous networks formed hydrogels with a high water absorption capacity. Finally, after showing cytocompatibility by the MTT assay, we also demonstrated the applicability of the porous hydrogels as scaffolds for cell cultivation. The presented results suggest that this type of hydrogels is a promising material for tissue engineering.

Biofire pneumonia panel in lung donors: faster detection but limited pathogens.

BACKGROUND: Culture of bronchoalveolar lavage (BAL) specimens takes time to report. We tested whether a molecular diagnostic test could accelerate donor lung assessment and treatment. METHODS: We compared BioFire Film Array Pneumonia Panel (BFPP) with standard of care (SOC) tests on lung allograft samples at three time points: (1) donor BAL at organ recovery, (2) donor bronchial tissue and airway swab at implantation, and (3) first recipient BAL following lung implantation. Primary outcomes were the difference in time to result (Wilcoxon signed-ranked tests) and the agreement in results between BFPP and SOC assays (Gwet's agreement coefficient). RESULTS: We enrolled 50 subjects. In donor lung BAL specimens, BFPP detected 52 infections (14 out of 26 pathogens in the panel). Viral and bacterial BFPP results were reported 2.4 h (interquartile range, IQR 2.0-6.4) following BAL versus 4.6 h (IQR 1.9-6.0, p = 0.625) for OPO BAL viral SOC results and 66 h (IQR 47-87, p < .0001) for OPO BAL bacterial SOC results. Although there was high overall agreement of results between BAL-BFPP versus OPO BAL-SOC tests (Gwet's AC p < .001 for all), the level of agreement differed among 26 pathogens designed in BFPP and differed by types of specimens. BFPP could not detect many infections identified by SOC assays. CONCLUSIONS: BFPP decreased time to detection of lung pathogens among donated lungs, but it cannot replace SOC tests due to the limited number of pathogens in the panel.

Polylactide-Based Materials: Synthesis and Biomedical Applications.

Polylactide (PLA) is a biocompatible polyester that can be obtained by polycondensation of lactic acid or the ring-opening polymerization (ROP) of lactide [...].

Lung preservation: from perfusion to temperature.

PURPOSE OF REVIEW: This article will review the evidence behind elements of the lung preservation process that have remained relatively stable over the past decade as well as summarize recent developments in ex-vivo lung perfusion and new research challenging the standard temperature for static cold storage. RECENT FINDINGS: Ex-vivo lung perfusion is becoming an increasingly well established means to facilitate greater travel distance and allow for continued reassessment of marginal donor lungs. Preliminary reports of the use of normothermic regional perfusion to allow utilization of lungs after DCD recovery exist, but further research is needed to determine its ability to improve upon the current method of DCD lung recovery. Also, research from the University of Toronto is re-assessing the optimal temperature for static cold storage; pilot studies suggest it is a feasible means to allow for storage of lungs overnight to allow for daytime transplantation, but ongoing research is awaited to determine if outcomes are superior to traditional static cold storage. SUMMARY: It is crucial to understand the fundamental principles of organ preservation to ensure optimal lung function posttransplant. Recent advances in the past several years have the potential to challenge standards of the past decade and reshape how lung transplantation is performed.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Preoperative Antithrombin Supplementation in Patients at Risk for Antithrombin Deficiency After Cardiac Surgery.

BACKGROUND: Antithrombin (AT) activity is reduced during cardiac operations with cardiopulmonary bypass (CPB), which is associated with adverse outcomes. Preoperative AT supplementation, to achieve >58% and <100% AT activity, may potentially reduce postoperative morbidity and mortality in cardiac operations with CPB. This prospective, multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate the safety and efficacy of preoperative treatment with AT supplementation in patients at risk for low AT activity after undergoing cardiac surgery with CPB. METHODS: A total of 425 adult patients were randomized (1:1) to receive either a single dose of AT (n = 213) to achieve an absolute increase of 20% above pretreatment AT activity or placebo (n = 212) before surgery. The study duration was approximately 7 weeks. The primary efficacy end point was the percentage of patients with any component of a major morbidity composite (postoperative mortality, stroke, acute kidney injury [AKI], surgical reexploration, arterial or venous thromboembolic events, prolonged mechanical ventilation, and infection) in the 2 groups. Secondary end points included AT activity, blood loss, transfusion requirements, duration of intensive care unit (ICU), and hospital stays. Safety was also assessed. RESULTS: Overall, 399 patients (men, n = 300, 75.2%) with a mean (standard deviation [SD]) age of 66.1 (11.7) years, with the majority undergoing complex surgical procedures (n = 266, 67.9%), were analyzed. No differences in the percentage of patients experiencing morbidity composite outcomes between groups were observed (AT-treated 68/198 [34.3%] versus placebo 58/194 [29.9%]; P = .332; relative risk, 1.15). After AT infusion, AT activity was significantly higher in the AT group (108% [42-143]) versus placebo group (76% [40-110]), and lasted up to postoperative day 2. At ICU, the frequency of patients with AT activity ≥58% in the AT group (81.5%) was significantly higher ( P < .001) versus placebo group (43.2%). Secondary end point analysis did not show any advantage of AT over placebo group. There were significantly more patients with AKI ( P < .001) in the AT group (23/198; 11.6%) than in the placebo group (5/194, 2.6%). Safety results showed no differences in treatment-emergent adverse events nor bleeding events between groups. CONCLUSIONS: AT supplementation did not attenuate adverse postoperative outcomes in our cohort of patients undergoing cardiac surgery with CPB.

Lung transplantation from swimming pool drowning victims: A case series.

The use of donor lungs from victims of drowning remains a rare occurrence, given concerns over lung parenchymal injury and microbial contamination secondary to aspiration. Given this infrequency, there is a relative paucity of literature surrounding the use of organs from drowned donors, with the few that exist on this subject focusing primarily on cases of drowning in naturally occurring bodies of water (i.e., drowning at sea). Little is known regarding the outcomes of utilizing donor lungs from victims of drowning in artificial bodies of water (i.e., swimming pools). Here, we describe three cases of bilateral lung transplantation from donors who drowned in swimming pools, with good short- and long-term outcomes. These cases lend further evidence to the feasibility of using such organs that have traditionally been viewed with much trepidation. With continually growing demand for donor organs, the use of drowned donor lungs may serve as a means to expand the donor pool and lessen the burden of waitlist mortality.

Modification of Polylactide Nonwovens with Carbon Nanotubes and Ladder Poly(silsesquioxane).

Electrospun nonwovens of poly(L-lactide) (PLLA) modified with multiwall carbon nanotubes (MWCNT) and linear ladder-like poly(silsesquioxane) with methoxycarbonyl side groups (LPSQ-COOMe) were obtained. MWCNT and LPSQ-COOMe were added to the polymer solution before the electrospinning. In addition, nonwovens of PLLA grafted to modified MWCNT were electrospun. All modified nonwovens exhibited higher tensile strength than the neat PLA nonwoven. The addition of 10 wt.% of LPSQ-COOMe and 0.1 wt.% of MWCNT to PLLA increased the tensile strength of the nonwovens 2.4 times, improving also the elongation at the maximum stress.

Biocompatible Polymers Combined with Cyclodextrins: Fascinating Materials for Drug Delivery Applications.

Cyclodextrins (CD) are a group of cyclic oligosaccharides with a cavity/specific structure that enables to form inclusion complexes (IC) with a variety of molecules through non-covalent host-guest interactions. By an elegant combination of CD with biocompatible, synthetic and natural polymers, different types of universal drug delivery systems with dynamic/reversible properties have been generated. This review presents the design of nano- and micro-carriers, hydrogels, and fibres based on the polymer/CD supramolecular systems highlighting their possible biomedical applications. Application of the most prominent hydrophobic aliphatic polyesters that exhibit biodegradability, represented by polylactide and polycaprolactone, is described first. Subsequently, particular attention is focused on materials obtained from hydrophilic polyethylene oxide. Moreover, examples are also presented for grafting of CD on polysaccharides. In summary, we show the application of host-guest interactions in multi-component functional biomaterials for controlled drug delivery.

Redefining marginality: donor lung criteria.

PURPOSE OF REVIEW: Despite an increase in lung transplantation globally, the waitlist mortality persists due to organ shortage. In order to keep up with the demand, the marginal lung donor criteria need to be revisited. The goal of this review is to redefine the lung donor criteria based on the most recent data. RECENT FINDINGS: Recent evidence indicates that lungs from donor with traditional extended criteria such as, age more than 55, PaO2/FiO2 threshold of less than 300, ischemia time more than 6 h, positive sputum microbiology, abnormal radiography no longer represent contraindications to lung transplantation by themselves. In addition, the introduction of new antiviral agents, organs from Hepatitis C positive donors, though not extended in the traditional sense, have shown positive outcomes. SUMMARY: The decision to use such organs, including those with smoking history, should be taken in totality weighing both donor and recipient characteristics. Hence, authors would advocate removing the term 'marginal' or 'extended' from lung donor criteria.

Lung transplant programs in developing countries: challenges, solutions, and outcomes.

PURPOSE OF REVIEW: The majority of lung transplants (LT) performed are in developed countries. In contrast, little is known about the status of LT in developing nations. The objective is to summarize the challenges, present solutions, and review outcomes of LT in developing countries. We hope this review will guide healthcare providers in such countries that are contemplating embarking on this journey. RECENT FINDINGS: The key challenges that programs in developing countries encountered included shortage and marginal quality of donated organs, lack of dedicated multi-disciplinary LT team, limited availability of advanced technology and high risk of post-transplant infections. Education and collaboration among government, public, and healthcare sectors was seen as fundamental to building and maintaining a successful program. Despite minimal resources and huge challenges, LT survival rates in developing countries improved and were comparable with outcomes reported by the International Society for Heart and Lung Transplantation (ISHLT) Registry. SUMMARY: Starting a new LT program is a daunting task that is complex and resource intensive, especially in developing countries. Improving outcomes indeed provide impetus to continue to persevere in this endeavor with support from all sectors. The findings presented here could help new programs to better anticipate and tackle challenges.

Time-efficient, goal-directed, and evidence-based teaching in the ICU.

PURPOSE OF REVIEW: Teaching in the stressful, high-acuity environment of the ICU is challenging. The intensivist-educator must use teaching strategies that are both effective and time-efficient, as well as evidence-based approaches to the ICU curriculum. This review provides an overview of pertinent educational theories and their implications on educational practices, a selection of effective teaching techniques, and a review on feedback. RECENT FINDINGS: Evidence supports the role of conceptual frameworks in providing the educator with a key perspective to obtain a deeper understanding of the factors contributing to an effective and goal-directed education in the ICU. The role of simulation training for technical and nontechnical skills acquisition is growing. Feedback is difficult to provide, but critical to facilitate learner success; frameworks, and approaches are becoming more standardized. SUMMARY: Direct teaching should be goal-oriented, sequential, and adjusted to the level of the learner. The ICU curriculum should optimize cognitive load, reduce stress that is unrelated to the activity, include resilience training, and help trainees deal with stressful clinical situations better. Simulation is a powerful tool to promote technical and nontechnical skills. Providing feedback is essential and a skill that can be taught and enhanced with structure, prompts, and tools.

Elevated donor plasminogen activator inhibitor-1 levels and the risk of primary graft dysfunction.

Primary graft dysfunction (PGD) following lung transplantation is associated with elevated recipient plasma levels of plasminogen activator inhibitor-1 (PAI-1) and the receptor for advanced glycation end products (RAGE). However, the significance of these biomarkers in the donor plasma is uncertain. We hypothesized that elevated donor plasma levels of PAI-1 and RAGE would be associated with recipient PGD. We carried out a prospective unmatched case-control study of double-lung transplant recipients between May 2014 and September 2015. We compared donor plasma levels of PAI-1 and RAGE using rank-sum tests and t tests, in 12 recipients who developed PGD grade 2 or 3 within 72 hours postoperatively with 13 recipients who did not. Recipients who developed PGD had higher donor plasma levels of PAI-1 than recipients who did not (median 2.7 ng/mL vs 1.4; P = .03). Recipients with PGD also had numerically higher donor plasma levels of RAGE than recipients without PGD, although this difference did not achieve statistical significance (median 1061 pg/mL vs 679; P = .12). Systemic inflammatory responses in the donor, as reflected by elevated plasma levels of PAI-1, may contribute to the risk of developing PGD. Rapid biomarker assessment of easily available plasma samples may assist in donor lung selection and risk stratification.

Best Practices for Postoperative Brain Health: Recommendations From the Fifth International Perioperative Neurotoxicity Working Group.

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%-40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed.

Metallo-Polymer Chain Extension Controls the Morphology and Release Kinetics of Microparticles Composed of Terpyridine-Capped Polylactides and their Stereocomplexes.

Control over morphology and porosity of supramolecular complexed polylactide (PLA) microparticles can be achieved by manipulation of the supramolecular interactions between their constituent polymeric building blocks. It is expected that such modular systems are ideal candidates to serve as degradable delivery carriers. In view of this goal, this study reports about a modular fabrication of biodegradable microparticles from terpyridine (TPy) and bisterpyridine (bisTPy) end-functionalized PLAs that can be transiently extended by chain association through differently strong complexation to three metal cations: Ni2+ , Co2+ , or Fe2+ . Further influence on the morphology of the particles can be exerted by hydrogen-bonding association of enantiomeric l- and d-PLA chains in the form of stereocomplexes. Both effects cause different stabilization of phase-separating TPy and bisTPy PLA micrograins in a process of droplet-based microfluidic particle templating, resulting in different forms of microparticle porosity. If the resulting particles are tailored such to be highly porous, they exhibit a faster release of a model drug, (S)-(+)-4-(3-amino-pyrrolidino)-7-nitrobenzo-furazan, than if they have smooth surfaces. As a result, control over the synthetic parameters, and hence, the particle porosity, can be used to tune the release profiles of drugs from the PLA microspheres.

Enhancing Feedback on Professionalism and Communication Skills in Anesthesia Residency Programs.

BACKGROUND: Despite its importance, training faculty to provide feedback to residents remains challenging. We hypothesized that, overall, at 4 institutions, a faculty development program on providing feedback on professionalism and communication skills would lead to (1) an improvement in the quantity, quality, and utility of feedback and (2) an increase in feedback containing negative/constructive feedback and pertaining to professionalism/communication. As secondary analyses, we explored these outcomes at the individual institutions. METHODS: In this prospective cohort study (October 2013 to July 2014), we implemented a video-based educational program on feedback at 4 institutions. Feedback records from 3 months before to 3 months after the intervention were rated for quality (0-5), utility (0-5), and whether they had negative/constructive feedback and/or were related to professionalism/communication. Feedback records during the preintervention, intervention, and postintervention periods were compared using the Kruskal-Wallis and χ tests. Data are reported as median (interquartile range) or proportion/percentage. RESULTS: A total of 1926 feedback records were rated. The institutions overall did not have a significant difference in feedback quantity (preintervention: 855/3046 [28.1%]; postintervention: 896/3327 [26.9%]; odds ratio: 1.06; 95% confidence interval, 0.95-1.18; P = .31), feedback quality (preintervention: 2 [1-4]; intervention: 2 [1-4]; postintervention: 2 [1-4]; P = .90), feedback utility (preintervention: 1 [1-3]; intervention: 2 [1-3]; postintervention: 1 [1-2]; P = .61), or percentage of feedback records containing negative/constructive feedback (preintervention: 27%; intervention: 32%; postintervention: 25%; P = .12) or related to professionalism/communication (preintervention: 23%; intervention: 33%; postintervention: 24%; P = .03). Institution 1 had a significant difference in feedback quality (preintervention: 2 [1-3]; intervention: 3 [2-4]; postintervention: 3 [2-4]; P = .001) and utility (preintervention: 1 [1-3]; intervention: 2 [1-3]; postintervention: 2 [1-4]; P = .008). Institution 3 had a significant difference in the percentage of feedback records containing negative/constructive feedback (preintervention: 16%; intervention: 28%; postintervention: 17%; P = .02). Institution 2 had a significant difference in the percentage of feedback records related to professionalism/communication (preintervention: 26%; intervention: 57%; postintervention: 31%; P < .001). CONCLUSIONS: We detected no overall changes but did detect different changes at each institution despite the identical intervention. The intervention may be more effective with new faculty and/or smaller discussion sessions. Future steps include refining the rating system, exploring ways to sustain changes, and investigating other factors contributing to feedback quality and utility.

Compatibilizing of cotton fabric with hydrophobic drug cover layer for anti-inflammatory performance with the implementation of ibuprofen.

This paper presents active analgesic and anti-inflammatory dressings based on cotton woven material with surface functionalization enabling drug implementation. For this purpose, lactide was polymerized on the surface of cotton textiles to achieve better compatibility with hydrophobic drug and polylactide (PLA)-based macromolecules. Subsequently, ibuprofen-loaded PLA and PLA-PEG were implemented through the exhausting method. Such material was tested for cytotoxicity (toward L929 mouse fibroblasts) and anti-inflammatory activity (towards human Hs68 fibroblasts) based on the secretion of pro-inflammatory cytokines IL-1ß and TNF-α. The results showed that the drug attachment and its performance are influenced by a combination of mercerization, bleaching and polylactide grafting, and the release of ibuprofen depends on the drug-loaded layer structure. Moreover, we show that cotton woven fabric with ibuprofen-loaded PLA and PLA-PEG cover layers had anti-inflammatory properties. These new dressings may open possibilities for developing prolonged analgesic and anti-inflammatory materials for wound healing or transdermal drug delivery.

Effect of aluminium oxide nanoparticles on long-acting oleogels laden with Sc-PLA-chitosan nanoparticles for anti-HIV therapy.

The development of a long-acting injectable drug delivery systems (DDS) of active pharmaceutical ingredients (API) holds great promise in addressing the challenges of treatment adherence, predominantly in HIV/AIDS. Polymers are inevitable carriers for the preparation of DDS, which are typically composed of polylactide (PLA), carbohydrates such as chitosan or cellulose derivatives. In this study, the tenofovir alafenamide (TAF) laden PLA-stereocomplex-chitosan nanoparticles (Sc-PLA-chitosan NPs) were developed through the spray-dried technique. These NPs had a mean particle size of 91 ± 8 nm and were incorporated into oleogels consisting of sesame oil and ethyl-cellulose. To enhance the syringeability of highly viscous oleogels, the commercially available aluminium oxide NPs were added with a size of 78 nm. The proposed DDS exhibits prolonged sustained release for up to 12 days in phosphate buffer pH 7.4. Noteworthy, the oleogels with Sc-PLA-chitosan NPs displayed extended tissue permeation properties indicating their potential long-acting in-vivo drug release. Collectively, this study recommends that the development of Sc-PLA-chitosan NPs-loaded oleogels represents a certainly adaptable long-acting injectables system for the delivery of APIs in the context of HIV/AIDS. This system is expected to contribute to improved and effective treatment adherence among patients infected with HIV and provide requisite therapeutic outcomes.

3D printing of dolutegravir-loaded polylactide filaments as a long-acting implantable system for HIV treatment.

3D printing was used to prepare implantable systems or tablets loaded with dolutegravir to explore their potential as long-acting implantables (LAIs). Our strategy relies on preparing a polylactide (PLA) filament loaded with the anti-HIV drug. Subsequently, 3D printing was performed under conditions that allowed the PLA to be simultaneously melted and the drug encapsulated within the printed strand. The dolutegravir release profiles indicated its sustained release for 47 days. Furthermore, neat and drug-loaded tablets were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), while their morphology was assessed by scanning electron microscopy (SEM). Finally, their biocompatibility was proved by MTT assay against ISO standards recommended L929 mouse and human Hs68 skin fibroblast cells. All the results indicated that the 3D printing of PLA-based tablets could produce customized medications with potential applications against HIV.

Spray-dried pH-sensitive chitosan microparticles loaded with Mycobacterium bovis BCG intended for supporting treatment of Helicobacter pylori infection.

Gram-negative spiral-shaped Helicobacter pylori (Hp) bacteria induce the development of different gastric disorders. The growing resistance of Hp to antibiotics prompts to search for new therapeutic formulations. A promising candidate is Mycobacterium bovis BCG (BCG) with immunomodulatory properties. Biodegradable mucoadhesive chitosan is a good carrier for delivering BCG mycobacteria to the gastric mucosal environment. This study aimed to show whether BCG bacilli are able to increase the phagocytic activity of Cavia porcellus-guinea pig macrophages derived from the bone marrow towards fluorescently labeled Escherichia coli. Furthermore, to encapsulate live BCG bacilli, in spray-dried chitosan microparticles (CHI-MPs), and assess the pH-dependent release of mycobacteria in pH conditions mimicking gastric (acidic) or gut (alkaline) milieu. Microparticles (MPs) were made of chitosan and coated with Pluronic F-127-(Plur) or N-Acetyl-D-Glucosamine-(GlcNAc) to increase the MPs resistance to low pH or to increase anti-Hp effect, respectively. Spray-drying method was used for microencapsulation of live BCG. The biosafety of tested CHI-MPs has been confirmed using cell models in vitro and the model of guinea pig in vivo. The CHI-MPs loaded with BCG released live mycobacteria at pH 3.0 (CHI-GlcNAc-MPs) or pH 8.0. (CHI-Plur-MPs). The CHI-MPs loaded with live BCG can be used for per os inoculation of Cavia porcellus to check the effectiveness of delivered mycobacteria in increasing anti-H. pylori host response.