Endoscopic Visualization of the Embolization Coil With Subsequent Endoscopic Therapy: A Case Report.

Severe gastrointestinal bleeding is a common presentation to the emergency department. In such settings, trans-arterial embolization (TAE) may be conducted to address the bleeding. However, in some circumstances, this treatment may fail. Over-the-scope clips (OTSCs) have also shown efficacy when the first-line treatment is unsuccessful, and in this case report, we describe what we believe is the first reported application of OTSCs after TAE with partial coil migration. The patient had initially arrived at the emergency department with severe gastrointestinal bleeding, and despite the usage of inotropes and TAE, the patient had developed severe rebleeding. She ultimately recovered well after the utilization of OTSCs. This case report highlights that this form of management may be a valuable endoscopic therapy in preventing further coil migration for patients with emergency gastrointestinal bleeding.

The synergy of dual faecal immunochemical and faecal calprotectin testing for accurate assessment of endoscopic and histological activity in inflammatory bowel disease.

Background: Faecal biomarkers are increasingly utilized for disease assessment in inflammatory bowel disease (IBD). Objectives: To characterize the relative and combined accuracy of faecal calprotectin (FC) and faecal immunochemical testing (FIT) for detecting endoscopic and histologically active disease in Crohn's disease (CD) and ulcerative colitis (UC), subdivided by disease location. Design: A prospective cohort study. Methods: Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited and performed both FC and FIT ±30 days of ileocolonoscopy. Endoscopic activity was assessed via the simplified endoscopic score for CD, Mayo endoscopic score for UC and histological activity graded as nil/mild/moderate. Receiver-operator curve analyses were utilized to assess the performance of FC and FIT per disease subtype and location. Results: In all, 137 (79 CD, 57 UC) patients were recruited. FC was more sensitive than FIT in detecting active endoscopic (CD: 91% versus 69%, UC: 94% versus 82%) and histological (CD: 86% versus 55%, UC 88% versus 56%) disease. However, FIT was more specific than FC in detecting active endoscopic (CD: 94% versus 56%, UC: 85% versus 69%) and histological (CD: 93% versus 55%, UC: 96% versus 70%) diseases. FIT was more sensitive and specific than FC in detecting active colonic CD (endoscopic activity: 94% versus 93%, histological activity: 92% versus 77%, respectively); however, it was poorly sensitive for active ileal CD (43% versus 89%). Conclusion: FC demonstrated higher sensitivity and FIT higher specificity for active IBD. Hence, dual testing was synergistic, displaying excellent performance characteristics across most IBD locations and subtypes, holding promise for future clinical application. Trial registration: Not applicable.

Controlling Colloidal Crystal Nucleation and Growth with Photolithographically Defined Templates.

Colloidal crystallization provides a means to synthesize hierarchical nanostructures by design and to use these complex structures for nanodevice fabrication. In particular, DNA provides a means to program interactions between particles with high specificity, thereby enabling the formation of particle superlattice crystallites with tailored unit cell geometries and surface faceting. However, while DNA provides precise control of particle-particle bonding interactions, it does not inherently present a means of controlling higher-level structural features such as the size, shape, position, or orientation of a colloidal crystallite. While altering assembly parameters such as temperature or concentration can enable limited control of crystallite size and geometry, integrating colloidal assemblies into nanodevices requires better tools to manipulate higher-order structuring and improved understanding of how these tools control the fundamental kinetics and mechanisms of colloidal crystal growth. In this work, photolithography is used to produce patterned substrates that can manipulate the placement, size, dispersity, and orientation of colloidal crystals. By adjusting aspects of the pattern, such as feature size and separation, we reveal a diffusion-limited mechanism governing crystal nucleation and growth. Leveraging this insight, patterns are designed that can produce wafer-scale substrates with arrays of nanoparticle superlattices of uniform size and shape. These design principles therefore bridge a gap between a fundamental understanding of nanoparticle assembly and the fabrication of nanostructures compatible with functional devices.

Management of minimal and overt hepatic encephalopathy with branched-chain amino acids: a review of the evidence.

Hepatic encephalopathy (HE) is a challenging complication of liver disease that is associated with substantial morbidity and mortality. Branched-chain amino acid (BCAA) supplementation in the management of HE is a debated topic. This narrative review aims to provide an up-to-date review of the topic and includes studies featuring patients with hepatocellular carcinoma. A review of the literature was performed using the online databases MEDLINE and EMBASE for studies between 2002 and December 2022. Keywords 'branched-chain amino acids', 'liver cirrhosis' and 'hepatic encephalopathy' were used. Studies were assessed for inclusion and exclusion criteria. Of 1045 citations, 8 studies met the inclusion criteria. The main outcomes reported for HE was changed in minimal HE (MHE) (n = 4) and/or incidence of overt HE (OHE) (n = 7). Two of the 4 studies reporting on MHE had improvement in psychometric testing in the BCAA group, but there was no change in the incidence of OHE in any of the 7 papers in the BCAA group. There were few adverse effects of BCAA supplementation. This review found weak evidence for BCAA supplementation for MHE, and no evidence for BCAAs for OHE. However, given the relative paucity and methodological heterogeneity of the current research, there is scope for future studies to examine the effects of varying timing, dosage, and frequency of BCAAs on outcomes such as HE. Importantly, research is also needed to examine BCAAs in conjunction with standard therapies for HE such as rifaximin and/or lactulose.

The Utility of Faecal Calprotectin, Lactoferrin and Other Faecal Biomarkers in Discriminating Endoscopic Activity in Crohn's Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Currently, faecal calprotectin (FC) is the predominate faecal biomarker utilised in clinical practice to monitor Crohn's disease (CD) activity. However, there are several potential faecal biomarkers described in the literature. We performed a meta-analysis to determine the accuracy of faecal biomarkers in discriminating endoscopic activity and mucosal healing in CD. METHODS: We searched the medical literature using MEDLINE, EMBASE, and PubMed from 1978 to 8 August 2022. Descriptive statistics, including sensitivity, specificity of the primary studies, their positive and negative likelihood ratios, and their diagnostic odds ratio (DOR), were calculated. The methodological quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS) criteria. RESULTS: The search found 2382 studies, of which 33 were included for analysis after screening. FC was found to have a pooled sensitivity and specificity, DOR, and negative predictive value (NPV) in discriminating active endoscopic disease (versus inactive) of 81%, 74%, 13.93, and 0.27, respectively. Faecal lactoferrin (FL) had a pooled sensitivity and specificity, DOR, and NPV in discriminating active endoscopic disease of 75%, 80%, 13.41, and 0.34, respectively. FC demonstrated a pooled sensitivity and specificity, DOR, and NPV of 88%, 72%, 18.17, and 0.19 in predicting mucosal healing. CONCLUSION: FC remains an accurate faecal biomarker. Further evaluation of the utility of novel faecal biomarkers is needed.

A Clinical-Scale Microfluidic Respiratory Assist Device with 3D Branching Vascular Networks.

Recent global events such as COVID-19 pandemic amid rising rates of chronic lung diseases highlight the need for safer, simpler, and more available treatments for respiratory failure, with increasing interest in extracorporeal membrane oxygenation (ECMO). A key factor limiting use of this technology is the complexity of the blood circuit, resulting in clotting and bleeding and necessitating treatment in specialized care centers. Microfluidic oxygenators represent a promising potential solution, but have not reached the scale or performance required for comparison with conventional hollow fiber membrane oxygenators (HFMOs). Here the development and demonstration of the first microfluidic respiratory assist device at a clinical scale is reported, demonstrating efficient oxygen transfer at blood flow rates of 750 mL min⁻1 , the highest ever reported for a microfluidic device. The central innovation of this technology is a fully 3D branching network of blood channels mimicking key features of the physiological microcirculation by avoiding anomalous blood flows that lead to thrombus formation and blood damage in conventional oxygenators. Low, stable blood pressure drop, low hemolysis, and consistent oxygen transfer, in 24-hour pilot large animal experiments are demonstrated - a key step toward translation of this technology to the clinic for treatment of a range of lung diseases.

Self-Assembling Systems for Optical Out-of-Plane Coupling Devices.

Micromirrors are used in integrated photonics to couple extraplanar light into the planar structure of a device by redirecting light via specular reflection. Compared with grating or prism-based couplers, micromirrors allow for coupling of light over a broader range of wavelengths, provided that the micromirror is fabricated with a specific 3D shape to ensure proper reflection angles. In principle, self-assembly methods could enable reliable, parallelizable fabrication of such devices with a high degree of precision by designing self-assembling components that produce the desired microscale geometry as their thermodynamic products. In this work, we use DNA-functionalized nanoparticles to assemble faceted crystallites with predetermined crystal shapes, and demonstrate with microscale retroreflectance measurements that these self-assembled nanoparticle arrays do indeed behave like optically flat mirrors. Furthermore, we show that the tilt angle of the micromirrors can be intentionally controlled by altering the crystallographic symmetry and preferred crystal orientations as a function of the self-assembly process, thereby altering the resulting specular angle in a programmable manner. Measurements of optical coupling from normal incidence into the substrate plane via an optical fiber confirm that the faceted structures can function as optical out-of-plane coupling devices, and coating these structures with reflective materials allows for high efficiency of light reflection in addition to the angular control. Together, these experiments demonstrate how self-assembled nanoparticle materials can be used to generate optically relevant architectures, enabling a significant step in the development of self-assembly as a materials fabrication tool for integrated optical devices.

Utility of panenteric capsule endoscopy for the detection of small-bowel Crohn's disease in patients with a normal magnetic resonance enterography: A prospective observational pilot study.

Background and Aim: Capsule endoscopy allows the direct visualization of the small bowel. We examined the diagnostic utility of a new modality, namely panenteric Crohn's capsule endoscopy (CE), in detecting active small-bowel Crohn's disease (CD) in those with normal magnetic resonance enterography (MRE). Methods: We prospectively recruited patients with a diagnosis of CD or suspected small-bowel CD in whom the MRE was normal. Inclusion criteria included abdominal symptoms and abnormal serum or fecal biomarkers. The primary outcome was the detection of active small-bowel CD (measured through the Lewis score [LS]). Secondary outcomes included change in Montreal classification for those with a pre-existing CD diagnosis, change in medical therapy, clinical activity, and biomarkers at baseline and 6 months, and quality-of-life measures. Results: A total of 22 patients with a diagnosis of CD or suspected new diagnosis were recruited, with CE complete to the caecum in 21 and 18/21 (86%) showing evidence of active small-bowel CD (LS > 135). Of the patients with a pre-existing diagnosis of CD, 9/11 (82%) had a change in Montreal classification. At 6 months following CE, 17/18 (94%) had clinician-directed change in therapy. This correlated with an improvement in the quality of life (P < 0.05 as per the Short Inflammatory Bowel Disease Questionnaire), a reduction in the Harvey Bradshaw index (median: 7-4, P < 0.001), and favorable CRP and albumin response. Conclusion: Crohn's CE is a useful diagnostic test for assessing active small-bowel CD when imaging is normal but clinical suspicion is high. Crohn's CE should be integrated into the diagnostic algorithm for small-bowel CD.

Multilayer Scaling of a Biomimetic Microfluidic Oxygenator.

Extracorporeal membrane oxygenation (ECMO) has been advancing rapidly due to a combination of rising rates of acute and chronic lung diseases as well as significant improvements in the safety and efficacy of this therapeutic modality. However, the complexity of the ECMO blood circuit, and challenges with regard to clotting and bleeding, remain as barriers to further expansion of the technology. Recent advances in microfluidic fabrication techniques, devices, and systems present an opportunity to develop new solutions stemming from the ability to precisely maintain critical dimensions such as gas transfer membrane thickness and blood channel geometries, and to control levels of fluid shear within narrow ranges throughout the cartridge. Here, we present a physiologically inspired multilayer microfluidic oxygenator device that mimics physiologic blood flow patterns not only within individual layers but throughout a stacked device. Multiple layers of this microchannel device are integrated with a three-dimensional physiologically inspired distribution manifold that ensures smooth flow throughout the entire stacked device, including the critical entry and exit regions. We then demonstrate blood flows up to 200 ml/min in a multilayer device, with oxygen transfer rates capable of saturating venous blood, the highest of any microfluidic oxygenator, and a maximum blood flow rate of 480 ml/min in an eight-layer device, higher than any yet reported in a microfluidic device. Hemocompatibility and large animal studies utilizing these prototype devices are planned. Supplemental Visual Abstract, http://links.lww.com/ASAIO/A769.

Toward intersectional and culturally relevant sex and gender analysis in health research.

Current institutional frameworks in sex- and gender-based analysis (SGBA) are promising, but significant gaps remain in their relation to recent developments in research praxis. In this paper we draw from our own experiences with a national health research funding agency, the Canadian Institutes of Health Research (CIHR), to critically examine the uptake and implementation of its current frameworks and practices of sex and gender analysis in health research. We conducted semi-structured interviews with a cohort of 18 health researchers alongside an institutional policy analysis to show how sex and gender have been understood, integrated, and addressed within the agency and initiative. Our findings reveal that attention to date has focused on representation (human and data) while deeper justice issues that are attentive to intersectionality, positionality and reflexivity-remain ambiguous. Finally, we discuss possible strategies for institutions to improve the uptake of knowledge, training, and policy to better support intersectional and culturally-relevant frameworks across the diverse research community.

Implementing Indigenous Gender-Based Analysis in Research: Principles, Practices and Lessons Learned.

Numerous tools for addressing gender inequality in governmental policies, programs, and research have emerged across the globe. Unfortunately, such tools have largely failed to account for the impacts of colonialism on Indigenous Peoples' lives and lands. In Canada, Indigenous organizations have advanced gender-based analysis frameworks that are culturally-grounded and situate the understanding of gender identities, roles, and responsibilities within and across diverse Indigenous contexts. However, there is limited guidance on how to integrate Indigenous gender-based frameworks in the context of research. The authors of this paper are participants of a multi-site research program investigating intersectoral spaces of Indigenous-led renewable energy development within Canada. Through introspective methods, we reflected on the implementation of gender considerations into our research team's governance and research activities. We found three critical lessons: (1) embracing Two-Eyed Seeing or Etuaptmumk while making space for Indigenous leadership; (2) trusting the expertise that stems from the lived experiences and relationships of researchers and team members; and (3) shifting the emphasis from 'gender-based analysis' to 'gender-based relationality' in the implementation of gender-related research considerations. Our research findings provide a novel empirical example of the day-to-day principles and practices that may arise when implementing Indigenous gender-based analysis frameworks in the context of research.

Design and construction of three-dimensional physiologically-based vascular branching networks for respiratory assist devices.

Microfluidic lab-on-a-chip devices are changing the way that in vitro diagnostics and drug development are conducted, based on the increased precision, miniaturization and efficiency of these systems relative to prior methods. However, the full potential of microfluidics as a platform for therapeutic medical devices such as extracorporeal organ support has not been realized, in part due to limitations in the ability to scale current designs and fabrication techniques toward clinically relevant rates of blood flow. Here we report on a method for designing and fabricating microfluidic devices supporting blood flow rates per layer greater than 10 mL min-1 for respiratory support applications, leveraging advances in precision machining to generate fully three-dimensional physiologically-based branching microchannel networks. The ability of precision machining to create molds with rounded features and smoothly varying channel widths and depths distinguishes the geometry of the microchannel networks described here from all previous reports of microfluidic respiratory assist devices, regarding the ability to mimic vascular blood flow patterns. These devices have been assembled and tested in the laboratory using whole bovine or porcine blood, and in a porcine model to demonstrate efficient gas transfer, blood flow and pressure stability over periods of several hours. This new approach to fabricating and scaling microfluidic devices has the potential to address wide applications in critical care for end-stage organ failure and acute illnesses stemming from respiratory viral infections, traumatic injuries and sepsis.

Toward Development of a Higher Flow Rate Hemocompatible Biomimetic Microfluidic Blood Oxygenator.

The recent emergence of microfluidic extracorporeal lung support technologies presents an opportunity to achieve high gas transfer efficiency and improved hemocompatibility relative to the current standard of care in extracorporeal membrane oxygenation (ECMO). However, a critical challenge in the field is the ability to scale these devices to clinically relevant blood flow rates, in part because the typically very low blood flow in a single layer of a microfluidic oxygenator device requires stacking of a logistically challenging number of layers. We have developed biomimetic microfluidic oxygenators for the past decade and report here on the development of a high-flow (30 mL/min) single-layer prototype, scalable to larger structures via stacking and assembly with blood distribution manifolds. Microfluidic oxygenators were designed with biomimetic in-layer blood distribution manifolds and arrays of parallel transfer channels, and were fabricated using high precision machined durable metal master molds and microreplication with silicone films, resulting in large area gas transfer devices. Oxygen transfer was evaluated by flowing 100% O2 at 100 mL/min and blood at 0-30 mL/min while monitoring increases in O2 partial pressures in the blood. This design resulted in an oxygen saturation increase from 65% to 95% at 20 mL/min and operation up to 30 mL/min in multiple devices, the highest value yet recorded in a single layer microfluidic device. In addition to evaluation of the device for blood oxygenation, a 6-h in vitro hemocompatibility test was conducted on devices (n = 5) at a 25 mL/min blood flow rate with heparinized swine donor blood against control circuits (n = 3). Initial hemocompatibility results indicate that this technology has the potential to benefit future applications in extracorporeal lung support technologies for acute lung injury.

Dynamic Manipulation of DNA-Programmed Crystals Embedded in a Polyelectrolyte Hydrogel.

DNA is a powerful tool for programming the three-dimensional organization of nanomaterials, where the specificity of nucleotide base-pairing can enable precise, complex, and dynamically addressable structures like colloidal crystals. However, because these DNA-programmed materials are often only stable in solution, their organization can be easily disrupted by changes to its local environment. Methods to stabilize these materials have been developed, but often come at the expense of altering or permanently fixing the materials' structures, removing many of the benefits of using DNA interactions to program assembly. Thus, these methods limit the application of DNA-assembled structures as dynamic and programmable material components. Here, a method is presented to resolve these drawbacks for DNA-grafted nanoparticles, also known as Programmable Atom Equivalents (PAEs), by embedding assembled lattices within a hydrogel matrix. The preformed lattices are exposed to polymerizable residues that electrostatically bind to the charged backbone of the DNA ligands and form a continuous, permeating gel network that stabilizes the colloidal crystals upon introduction of a radical initiator. After embedding PAEs in a hydrogel, deformation of the macroscopic matrix results in concomitant deformation of the PAE lattices, allowing superlattice structural changes to be induced by chemical methods (such as changing solute concentration to alter swelling pressure) or by application of mechanical strain. Changes to the structure of the PAE lattices are reversible and repeatable over multiple cycles and can be either isotropic (such as by swelling) or anisotropic (such as by mechanical deformation). This method of embedding nanoparticle crystals inside of a flexible and environmentally responsive hydrogel is therefore a useful tool in extending the utility of PAEs and other micro- and nanostructures assembled with DNA.

A high gas transfer efficiency microfluidic oxygenator for extracorporeal respiratory assist applications in critical care medicine.

Advances in microfluidics technologies have spurred the development of a new generation of microfluidic respiratory assist devices, constructed using microfabrication techniques capable of producing microchannel dimensions similar to those found in human capillaries and gas transfer films in the same thickness range as the alveolar membrane. These devices have been tested in laboratory settings and in some cases in extracorporeal animal experiments, yet none have been advanced to human clinical studies. A major challenge in the development of microfluidic oxygenators is the difficulty in scaling the technology toward high blood flows necessary to support adult humans; such scaling efforts are often limited by the complexity of the fabrication process and the manner in which blood is distributed in a three-dimensional network of microchannels. Conceptually, a central advantage of microfluidic oxygenators over existing hollow-fiber membrane-based configurations is the potential for shallower channels and thinner gas transfer membranes, features that reduce oxygen diffusion distances, to result in a higher gas transfer efficiency defined as the ratio of the volume of oxygen transferred to the blood per unit time to the active surface area of the gas transfer membrane. If this ratio is not significantly higher than values reported for hollow fiber membrane oxygenators (HFMO), then the expected advantage of the microfluidic approach would not be realized in practice, potentially due to challenges encountered in blood distribution strategies when scaling microfluidic designs to higher flow rates. Here, we report on scaling of a microfluidic oxygenator design from 4 to 92 mL/min blood flow, within an order of magnitude of the flow rate required for neonatal applications. This scaled device is shown to have a gas transfer efficiency higher than any other reported system in the literature, including other microfluidic prototypes and commercial HFMO cartridges. While the high oxygen transfer efficiency is a promising advance toward clinical scaling of a microfluidic architecture, it is accompanied by an excessive blood pressure drop in the circuit, arising from a combination of shallow gas transfer channels and equally shallow distribution manifolds. Therefore, next-generation microfluidic oxygenators will require novel design and fabrication strategies to minimize pressure drops while maintaining very high oxygen transfer efficiencies.

If only they had accessed the data: Governmental failure to monitor pulp mill impacts on human health in Pictou Landing First Nation.

For over fifty years, Pictou Landing First Nation (PLFN), a small Mi'kmaw community on the northern shore of mainland Nova Scotia, Canada, has been told by a Joint Environmental Health Monitoring Committee (JEHMC) mandated to oversee the health of the community that their health has not been impacted by exposure to 85 million litres of pulp mill effluent dumped every day into what was once a culturally significant body of water bordering their community. Yet, based on lived experience, the community knows otherwise, and despite countless dollars spent on government and industry-sponsored research, their concerns have not gone away. Using biopolitical theory, we explore why JEHMC never fully implemented its mandate. We will use a Mi'kmaw environmental 'theoretical' framework to demonstrate that indicators of a relational epistemology and ontology that have been consistently and persistently overlooked in Indigenous environmental health research demands that Indigenous connections to the air, land and water must be taken into consideration to get a full understanding of environmental health impacts. Guided by the principle of Etuaptmumk (Two-Eyed Seeing), which brings together the strengths of both western and Indigenous knowledge, and employing a community-based participatory research approach, we use data that could have been accessed by the JEHMC that might have signaled that human health studies were warranted. Further, we developed an environmental health survey that more appropriately assesses the impacts on the community. Finally, we will discuss how an Indigenous-developed framework can adequately assess the impacts of land displacement and environmental dispossession on the health of Indigenous communities and illustrate how our framework can serve as a guide to others when exploring Indigenous environmental health more broadly.

Stop ringing the alarm; it is time to get out of the building!

The volume of calls for governments and public health officials to take concerted action on climate change has become almost deafening. Public health researchers and practitioners need to look beyond what we know about the health impacts of climate change, to what we are doing as our part in contributing to holding global temperature rise to under 1.5°C. This commentary reflects on the common threads across the articles of a special section in this issue of the Canadian Journal of Public Health, "Moving on IPCC 1.5°C", which sought examples of bold research and action advancing climate change mitigation and adaptation. Among the articles, there are signs that the public health community is gaining momentum in confronting the climate crisis. Three critical lessons emerged: the need for institutional change from the top of public health, the essential power of community in intersectoral action on climate change preparedness, and the importance of centring Indigenous wisdom to decolonize colonial legacy systems. We encourage readers to move public health research and practice from an instrumental relationship with nature to one of reverence and sacred reciprocity.

RéSUMé: Le volume des appels aux gouvernements et aux autorités de santé publique à agir de concert face aux changements climatiques devient assourdissant. Au-delà de ce que nous savons des effets des changements climatiques sur la santé, les chercheurs et les praticiens en santé publique doivent examiner ce que nous faisons pour maintenir la hausse de la température mondiale en deçà de 1,5 °C. Dans ce commentaire, nous réfléchissons à la trame commune des articles d'une rubrique spéciale dans ce numéro de la Revue canadienne de santé publique, « Réaction au cri d'alarme du GIEC ¼, qui sollicitait des exemples d'études et de mesures audacieuses pour faire progresser l'atténuation des changements climatiques et l'adaptation à ces changements. Dans les articles de la rubrique, il y a des signes que la communauté de la santé publique se mobilise pour faire face à la crise climatique. Trois leçons essentielles s'en dégagent : la nécessité d'un changement institutionnel au sommet de la santé publique, le pouvoir essentiel de la communauté dans l'action intersectorielle de préparation aux changements climatiques, et l'importance de miser sur la sagesse autochtone pour décoloniser les systèmes hérités du colonialisme. Nous encourageons nos lecteurs à faire passer la recherche et la pratique en santé publique d'une relation instrumentale avec la nature à une relation de révérence et de réciprocité sacrée.