Bridging Formal Shape Models and Deep Learning: A Novel Fusion for Understanding 3D Objects.

This article describes a novel fusion of a generative formal model for three-dimensional (3D) shapes with deep learning (DL) methods to understand the geometric structure of 3D objects and the relationships between their components, given a collection of unorganized point cloud measurements. Formal 3D shape models are implemented as shape grammar programs written in Procedural Shape Modeling Language (PSML). Users write PSML programs to describe complex objects, and DL networks estimate the configured free parameters of the program to generate 3D shapes. Users write PSML programs to enforce fundamental rules that define an object class and encode object attributes, including shapes, components, size, position, etc., into a parametric representation of objects. This fusion of the generative model with DL offers artificial intelligence (AI) models an opportunity to better understand the geometric organization of objects in terms of their components and their relationships to other objects. This approach allows human-in-the-loop control over DL estimates by specifying lists of candidate objects, the shape variations that each object can exhibit, and the level of detail or, equivalently, dimension of the latent representation of the shape. The results demonstrate the advantages of the proposed method over competing approaches.

UAV-Borne Mapping Algorithms for Low-Altitude and High-Speed Drone Applications.

This article presents an analysis of current state-of-the-art sensors and how these sensors work with several mapping algorithms for UAV (Unmanned Aerial Vehicle) applications, focusing on low-altitude and high-speed scenarios. A new experimental construct is created using highly realistic environments made possible by integrating the AirSim simulator with Google 3D maps models using the Cesium Tiles plugin. Experiments are conducted in this high-realism simulated environment to evaluate the performance of three distinct mapping algorithms: (1) Direct Sparse Odometry (DSO), (2) Stereo DSO (SDSO), and (3) DSO Lite (DSOL). Experimental results evaluate algorithms based on their measured geometric accuracy and computational speed. The results provide valuable insights into the strengths and limitations of each algorithm. Findings quantify compromises in UAV algorithm selection, allowing researchers to find the mapping solution best suited to their application, which often requires a compromise between computational performance and the density and accuracy of geometric map estimates. Results indicate that for UAVs with restrictive computing resources, DSOL is the best option. For systems with payload capacity and modest compute resources, SDSO is the best option. If only one camera is available, DSO is the option to choose for applications that require dense mapping results.

The Effects of Protrusion into the Outflow Vein on Outcomes of Stent Grafts Used to Treat Cephalic Arch Stenoses in Dysfunctional Brachiocephalic Fistulae.

PURPOSE: To assess long-term patency rates of cephalic arch stent grafts in brachiocephalic fistulae and the importance of device position. MATERIALS AND METHODS: This retrospective study reviewed 152 patients with dysfunctional brachiocephalic fistulae and cephalic arch stenosis treated with stent grafts (Viabahn; W. L. Gore) at a single tertiary center between 2012 and 2021. The median age was 67.5 years (range, 25-91 years), and the median follow-up period was 637 days (range, 3-3,368 days). A grading system of protrusion was applied: (a) Grade 0, no protrusion; (b) Grade 1, perpendicular; and (c) Grade 2, in-line protrusion. Subsequent fistulograms were available in 133 (88%) of the 152 patients and were assessed for central vein stenosis within 10 mm of the stent graft. Clinical records were assessed for sequelae of stent graft protrusion. Stent graft primary and cumulative circuit patencies were calculated using the Kaplan-Meier method. RESULTS: Protrusion was documented in 106 (70%) stent grafts-56 Grade 1 and 50 Grade 2. Central vein stenosis was seen in 1 (2%) case of no protrusion (Grade 0) and 38 (40%) cases of protrusion (P < .0001). There was no significant difference in stenosis between Grade 1 and 2 protrusion (P = .15). No adverse clinical sequelae occurred in 147 (97%) patients. Eight patients had a new access subsequently formed in the same arm, and 3 of these 8 patients developed symptoms due to the previous stent graft protrusion (all Grade 2). The primary patency rates of the stent-grafts at 6 and 12 months were 73% and 50%, respectively. The cumulative access circuit patency rates at 1, 2, and 5 years were 84%, 72%, and 54%, respectively. CONCLUSIONS: This study demonstrated that protrusion of a cephalic arch stent graft into the central vein is safe and only clinically relevant when a subsequent ipsilateral access is created.

Widening participation - recruitment methods in mental health randomised controlled trials: a qualitative study.

BACKGROUND: Barriers to mental health research participation are well documented including distrust of services and research; and stigma surrounding mental health. They can contribute to a lack of diversity amongst participants in mental health research, which threatens the generalisability of knowledge. Given the recent widespread use of the internet in medical research, this study aimed to explore the perspectives of key partners on the use of online (e.g. social media) and offline (e.g. in-person) recruitment as an approach to improving diversity in mental health randomised controlled trials (RCTs). METHODS: Face-to-face and online interviews/focus groups with researchers working in mental health and Patient and Public Involvement partners in the United Kingdom. Recordings were transcribed and analysed using a combination of inductive and deductive thematic analysis. RESULTS: Three focus groups and three interviews were conducted with a total N = 23 participants. Four overarching themes were identified: (1) recruitment reach; (2) Demographic factors that affect selection of recruitment method; (3) safety of technology, and; (4) practical challenges. Five main factors were identified that affect the choice of recruitment method: age, complexity of mental health problem and stigma, cultural and ethnicity differences and digital divide. The use of online methods was considered more accessible to people who may feel stigmatised by their mental health condition and with a benefit of reaching a wider population. However, a common view amongst participants was that online methods require closer data monitoring for quality of responders, are not fully secure and less trustworthy compared to offline methods that enable participants to build relationships with health providers. Funding, staff time and experience, organisational support, and technical issues such as spam or phishing emails were highlighted as practical challenges facing online recruitment. All participants agreed that using a hybrid approach tailored to the population under study is paramount. CONCLUSIONS: This study highlighted the importance of offering a flexible and multifaceted recruitment approach by integrating online with offline methods to support inclusivity and widening participation in mental health research. The findings will be used to develop considerations for researchers designing RCTs to improve recruitment in mental health research.

Individual, healthcare professional and system-level barriers and facilitators to initiation and adherence to injectable therapies for type 2 diabetes: A systematic review and meta-ethnography.

AIMS: To review and synthesise the contemporary qualitative evidence, relating to the individual, healthcare professional and system-level barriers and facilitators to injectable therapies in people with type 2 diabetes, and evaluate (using an intersectional approach to explore the diverse perspectives of different identities) whether views have changed with treatment and guideline advancements. METHODS: A meta-ethnography approach used. Eight databases searched from the years 2006 (GLP-1 analogues introduced) to February 2021. Study selection (using a pre-defined inclusion criteria), quality appraisal and data extraction, conducted independently by two reviewers. RESULTS: Screened 7143 abstracts, assessed 93 full-text papers for eligibility and included 42 studies-using data from 818 individuals with type 2 diabetes and 160 healthcare professionals. Studies covered a diverse range of views from healthcare professionals and individuals, including those relating to older adults and people from ethnic migrant backgrounds, and 10 studies rated moderate to strong research value. Key themes abstracted: barriers (physical/psychological/social) and facilitators (motivation/capability/opportunity). CONCLUSIONS: The first synthesis of contemporary qualitative data to adopt an intersectionality approach and explore diverse views relating to barriers and facilitators that influence engagement with injectable treatments for type 2 diabetes. A model is presented to help patients, health practitioners and policy makers identify barriers and facilitators and understand the complex interplay of physical, psychological and social factors involved when prescribing injectable therapies. Despite advances in injectable treatments and guidelines, findings highlight the many barriers that still exist and show how strongly held culturally-specific health beliefs of people from diverse socio-economic and ethnic backgrounds can become substantial obstacles to treatment.

Low-Bandwidth and Compute-Bound RGB-D Planar Semantic SLAM.

Visual simultaneous location and mapping (SLAM) using RGB-D cameras has been a necessary capability for intelligent mobile robots. However, when using point-cloud map representations as most RGB-D SLAM systems do, limitations in onboard compute resources, and especially communication bandwidth can significantly limit the quantity of data processed and shared. This article proposes techniques that help address these challenges by mapping point clouds to parametric models in order to reduce computation and bandwidth load on agents. This contribution is coupled with a convolutional neural network (CNN) that extracts semantic information. Semantics provide guidance in object modeling which can reduce the geometric complexity of the environment. Pairing a parametric model with a semantic label allows agents to share the knowledge of the world with much less complexity, opening a door for multi-agent systems to perform complex tasking, and human-robot cooperation. This article takes the first step towards a generalized parametric model by limiting the geometric primitives to a planar surface and providing semantic labels when appropriate. Two novel compression algorithms for depth data and a method to independently fit planes to RGB-D data are provided, so that plane data can be used for real-time odometry estimation and mapping. Additionally, we extend maps with semantic information predicted from sparse geometries (planes) by a CNN. In experiments, the advantages of our approach in terms of computational and bandwidth resources savings are demonstrated and compared with other state-of-the-art SLAM systems.

Validation of a point-of-care polymerase chain reaction assay for detection of Streptococcus equi subspecies equi in rostral nasal swabs from horses with suspected strangles.

This study aimed to validate a point-of-care polymerase chain reaction (PCR) assay for detection of Streptococcus equi subsp. equi (S. equi) in rostral nasal swabs from horses with suspected acute strangles and to compare the results against the molecular gold standard of quantitative polymerase chain reaction (qPCR). Two hundred thirty-two individual swabs of rostral nasal passages were characterized by qPCR as S. equi positive, S. equi subsp. zooepidemicus (S. zooepidemicus) positive, or S. equi and S. zooepidemicus negative. The specificity and sensitivity of the point-of-care PCR assay were 89% and 84%, respectively. The limits of detection of the qPCR assay and the point-of-care PCR analyzer were 3 and 277 eqbE target genes of S. equi, respectively. Overall agreement and short turnaround time make the point-of-care PCR assay a potential molecular diagnostic platform that will enhance the capability of equine veterinarians to timely support a diagnosis of strangles and institute proper biosecurity protocols.

Validation d'une épreuve d'amplification en chaîne par la polymérase au point de service pour la détection de Streptococcus equi sous-espèce equi dans des écouvillons nasaux rostraux de chevaux suspectés d'avoir la gourme. La présente étude visait à valider une épreuve d'amplification en chaîne par la polymérase (PCR) au point de service pour la détection de Streptococcus equi ssp. equi (S. equi) à partir d'écouvillons nasaux rostraux de chevaux suspectés être atteints de gourme aiguë et de comparer les résultats à ceux de l'épreuve étalon de la réaction d'amplification en chaîne par la polymérase quantitative (qPCR). Deux cent trente-deux écouvillons individuels des voies nasales rostrales furent caractérisés par qPCR comme étant S. equi positif, S. equi ssp. zooepidemicus (S. zooepidemicus) positif ou S. equi et S. zooepidemicus négatifs. La spécificité et la sensibilité de l'épreuve PCR au point de service étaient de 89 % et 84 %, respectivement. Les limites de détection de l'épreuve par qPCR et de l'analyseur PCR au point de service étaient de 3 et 277 copies du gène cible eqbE de S. equi, respectivement. L'accord général et le court temps de réponse font du PCR au point de service une plate-forme de diagnostic moléculaire potentielle qui augmentera les capacités des vétérinaires équins à appuyer adéquatement un diagnostic de gourme et d'instituer les protocoles de biosécurité appropriés.(Traduit par Dr Serge Messier).

Results of Stent Graft Placement to Treat Cephalic Arch Stenosis in Hemodialysis Patients with Dysfunctional Brachiocephalic Arteriovenous Fistulas.

PURPOSE: To determine effectiveness of the VIABAHN (W.L. Gore & Associates, Flagstaff, Arizona) stent graft to treat cephalic arch stenosis in patients with dysfunctional brachiocephalic arteriovenous fistulas after inadequate venoplasty response. MATERIALS AND METHODS: Between 2012 and 2015, patients with failed venoplasty of symptomatic cephalic arch stenosis received a VIABAHN stent graft. Follow-up venography was performed at approximately 3, 6, and 12 months. Data were retrospectively analyzed with patency estimated using Kaplan-Meier and log-rank methodology. There were 39 patients included. RESULTS: Technical and clinical success was 100%. Primary target lesion patency was 85% (95% confidence interval [CI], 69%-93%), 67% (95% CI, 50%-80%), and 42% (95% CI, 25%-57%) at 3, 6, and 12 months. There was no significant difference in patency with regard to sex or age (P = .8 and P = .6, respectively). Primary assisted patency was 95% (95% CI, 82%-99%) at 3, 6, and 12 months. Access circuit primary patency was 85% (95% CI, 69%-93%), 67% (95% CI, 50%-80%), and 42% (95% CI, 25%-57%) at 3, 6, and 12 months. There was no significant difference in patency between patients with the stent graft as the first treatment episode in the cephalic arch and those that had previous intervention at this site (P = .98). There were 48 repeat venoplasty procedures performed in the cephalic arch to maintain patency, including 7 repeat VIABAHN insertions. No complications were encountered. CONCLUSIONS: The VIABAHN stent graft is a safe, effective, and durable device for treating cephalic arch stenosis when venoplasty fails.

Reporting and representation of underserved groups in intervention studies for patients with multiple long-term conditions: a systematic review.

OBJECTIVES: Globally, there is a growing number of people who are living with multiple long-term conditions (MLTCs). Due to complex management needs, it is imperative that research consists of participants who may benefit most from interventions. It is well documented that ethnic minority groups and lower socioeconomic status (SES) groups are at an increased risk of developing MLTCs. Therefore, the aim of this systematic review was to determine the level of reporting and representation of underserved groups (ethnic minority and low SES) in intervention studies addressing MLTCs. DESIGN: Systematic review. Four databases including Cochrane Library, MEDLINE, CINAHL and Scopus were searched for intervention studies from North America or Europe published between January 1990 and July 2023. SETTING: Hospital and community-based interventions. We included interventional studies focusing on improving MLTC-related outcomes. PARTICIPANTS: Patients with MLTCs. MAIN OUTCOME MEASURES: Total number of studies reporting on ethnicity and SES. Number and proportion of studies reporting by ethnic/SES group. RESULTS: Thirteen studies met the inclusion criteria. Only 4 of 13 studies (31%) recorded and reported ethnicity information. Of these four studies that reported on ethnicity, three studies consisted of primarily White participants. Ethnic minority groups were underrepresented, but one study included a majority of African American participants. Moreover, 12 of 13 studies (92%) reported on SES with income and educational level being the primary measures used. SES representation of higher deprivation groups was varied due to limited data. CONCLUSIONS: For ethnicity, there was a lack of reporting, and ethnic minority groups were underrepresented in intervention studies. For SES, there was a high level of reporting but the proportion of study samples from across the spectrum of SES varied due to the variety of SES measures used. Findings highlight a need to improve the reporting and representation of ethnic minority groups and provide more detailed information for SES through using consistent measures (e.g. education, income and employment) to accurately determine the distribution of SES groups in intervention studies of people with MLTCs.

Clinicopathological and pedigree investigation of a novel spinocerebellar neurological disease in juvenile Quarter Horses in North America.

BACKGROUND: In 2020, a novel neurologic disease was observed in juvenile Quarter Horses (QHs) in North America. It was unknown if this was an aberrant manifestation of another previously described neurological disorder in foals, such as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). HYPOTHESIS/OBJECTIVES: To describe the clinical findings, outcomes, and postmortem changes with Equine Juvenile Spinocerebellar Ataxia (EJSCA), differentiate the disease from other similar neurological disorders, and determine a mode of inheritance. ANIMALS: Twelve neurologically affected QH foals and the dams. METHODS: Genomic DNA was isolated and pedigrees were manually constructed. RESULTS: All foals (n = 12/12) had a history of acute onset of neurological deficits with no history of trauma. Neurological deficits were characterized by asymmetrical spinal ataxia, with pelvic limbs more severely affected than thoracic limbs. Clinicopathological abnormalities included high serum activity of gamma-glutamyl transferase and hyperglycemia. All foals became recumbent (median, 3 days: [0-18 days]), which necessitated humane euthanasia (n = 11/12, 92%; the remaining case was found dead). Histological evaluation at postmortem revealed dilated myelin sheaths and digestion chambers within the spinal cord, most prominently in the dorsal spinocerebellar tracts. Pedigree analysis revealed a likely autosomal recessive mode of inheritance. CONCLUSIONS AND CLINICAL IMPORTANCE: EJSCA is a uniformly fatal, rapidly progressive, likely autosomal recessive neurological disease of QHs <1 month of age in North America that is etiologically distinct from other clinically similar neurological disorders. Once the causative variant for EJSCA is validated, carriers can be identified through genetic testing to inform breeding decisions.

Cardiovascular disease prevention: Community Based Asset Mapping within religious networks in a rural Sub-Saharan African neighbourhood.

Prevalence of conditions which raise cardiovascular risk, such as hypertension and type 2 diabetes are seeing a dramatic rise in Sub Saharan Africa. A large proportion of these cases remain undiagnosed and there is limited resource to provide patients with self-management support and education once diagnosed. This study aimed to identify and catalogue community-based assets for the purposes of developing and deploying a screening and education programme for cardiometabolic risk factors (diabetes and hypertension) within religious organisations in a local community in a rural Ghanaian context. We utilised a community-based form of participatory research made up of a number of different components including community-based asset mapping and stakeholder consultation, supplemented by 18 in-depth interviews and 10 focus groups with n = 115 service users, to map existing assets with relevance to cardiometabolic health in this setting and context. Thematic analysis of interview and focus group data was performed to identify themes related to successful implementation of health screening. Two stakeholder workshops with local healthcare professionals, faith leaders and health policy makers were delivered to co-produced a prioritised list of recommendations and 'asset map' to aid deployment of mass screening within faith organisations in this context. The findings of this research highlight a number of 'hidden' community assets and motivational mechanisms at an individual, community and institutional levels; these have informed a list of recommendations which have been co-developed with the stakeholder group and local community to support the development of effective screening strategies for cardiometabolic conditions within faith organisations in this context. We have identified key mechanisms and assets which would support a sustainable screening approach designed to engage an underserved community at high CVD risk to promote general community health and well-being.

Use of a VBX balloon expandable stent-graft for management of right brachiocephalic vein stenosis.

Here we describe the use of a VBX balloon expandable stent-graft (WL Gore, Flagstaff, AZ, USA) to treat a right brachiocephalic vein stenosis in a haemodialysis patient prior to ipsilateral upper limb arterio-venous (AV) fistula formation. Balloon expandable stent-grafts are unsuitable for treating peripheral fistula stenoses due to their susceptibility of being crushed. The right brachiocephalic vein is both relatively short in comparison to the left and is less susceptible to extrinsic compression and the use of such a device to treat stenosis here allows for very accurate placement and restoration of luminal diameter. The advantages and disadvantages of using these devices in haemodialysis access circuits are also discussed herein, in what we believe to be the first report of the application of a dedicated commercially available balloon expandable stent graft in a haemodialysis patient.

Randomised controlled trial of an innovative hypoglycaemia pathway for self-care at home and admission avoidance: a partnership approach with a regional ambulance trust.

Background: Hypoglycaemia is a common and potentially life-threatening condition in people with diabetes, commonly caused by medications such as insulin. Hypoglycaemic events often require in-patient treatment and/or follow-up with a diabetes specialist nurse (DSN) or GP to make adjustments to medication. This referral pathway commonly relies on patient self-referral to primary care, and as a result many patients are not actively followed up and go on to experience repeat hypoglycaemic events. Methods: Randomised controlled trial in partnership with East Midlands Ambulance Service NHS Trust. People with diabetes calling out an ambulance for a severe hypoglycaemic episode and meeting the eligibility criteria were randomised to either a novel DSN-led pathway or to their general practice for routine follow-up. Primary outcome was proportion of participants with a documented consultation with a healthcare professional to discuss the management of their diabetes within 28 days of call-out. Results: 162 people were randomised to one of the pathways (73 DSN arm, 89 GP arm) with 81 (50%, 35 DSN, 46 GP) providing full consent to be followed up. Due to lower than anticipated randomisation and consent rates, the recruitment target was not met. In the 81 participants who provided full consent, there were higher rates of consultation following the call-out when referred to a DSN compared to primary care (90% vs. 65%). Of the 81 participants, 26 (32%) had a second call-out within 12 months. Conclusions: Consultation rates following the call-out were high in the DSN-led arm, but there was insufficient power to complete the planned comparative analysis. The study highlighted the difficulty in recruitment and delivery of research in pre-hospital emergency care. Further work is needed to provide more feasible study designs and consent procedures balancing demands on ambulance staff time with the need for robust well-designed evaluation of referral pathways.

Trial Forge Guidance 3: randomised trials and how to recruit and retain individuals from ethnic minority groups-practical guidance to support better practice.

Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities.This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations.We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful.

Long-term results of stent-graft placement to treat central venous stenosis and occlusion in hemodialysis patients with arteriovenous fistulas.

PURPOSE: To determine the effectiveness of stent-grafts for the treatment of central venous disease in hemodialysis patients with functioning arteriovenous (AV) fistulas. MATERIALS AND METHODS: Between October 2004 and March 2010, 42 VIABAHN stent-grafts were deployed in central veins of 30 patients (16 men, 14 women; mean age 60 y) with functioning AV fistulas and central venous disease that did not respond to percutaneous transluminal angioplasty (PTA). Eighteen patients had central vein stenosis and 12 had occlusion. Previous PTA and/or bare metal stent placement had been performed in 23 patients (77%). Surveillance was carried out at 3, 6, 9, 12, 18, and 24 months with diagnostic fistulography. The mean follow-up was 705 days (range, 66-1,645 d). Statistical analysis included Kaplan-Meier and log-rank studies. RESULTS: Technical success rate was 100%. Primary patency rates were 97%, 81%, 67%, and 45% at 3, 6, 12, and 24 months, respectively. Primary assisted patency rates were 100%, 100%, 80%, and 75% at 3, 6, 12, and 24 months, respectively. Patients without previous procedures had significantly shorter times to repeat intervention (P = .018) than those who had undergone PTA or bare metal stent placement previously. Patients with occlusive lesions had a significantly shorter primary patency interval (P = .05) than patients with stenoses. Occluded veins were more likely to require further stent-grafts (P = .02). Twelve patients required further stent-grafts to maintain patency. There was one minor complication. CONCLUSIONS: Stent-graft placement to treat central venous disease in hemodialysis patients with autogenous AV fistulas is safe and effective if PTA fails to maintain luminal patency.

A system for 3D reconstruction of comminuted tibial plafond bone fractures.

High energy impacts at joint locations often generate highly fragmented, or comminuted, bone fractures. Current approaches for treatment require physicians to decide how to classify the fracture within a hierarchy fracture severity categories. Each category then provides a best-practice treatment scenario to obtain the best possible prognosis for the patient. This article identifies shortcomings associated with qualitative-only evaluation of fracture severity and provides new quantitative metrics that serve to address these shortcomings. We propose a system to semi-automatically extract quantitative metrics that are major indicators of fracture severity. These include: (i) fracture surface area, i.e., how much surface area was generated when the bone broke apart, and (ii) dispersion, i.e., how far the fragments have rotated and translated from their original anatomic positions. This article describes new computational tools to extract these metrics by computationally reconstructing 3D bone anatomy from CT images with a focus on tibial plafond fracture cases where difficult qualitative fracture severity cases are more prevalent. Reconstruction is accomplished within a single system that integrates several novel algorithms that identify, extract and piece-together fractured fragments in a virtual environment. Doing so provides objective quantitative measures for these fracture severity indicators. The availability of such measures provides new tools for fracture severity assessment which may lead to improved fracture treatment. This paper describes the system, the underlying algorithms and the metrics of the reconstruction results by quantitatively analyzing six clinical tibial plafond fracture cases.

Bone Morphogenetic Protein 7 Gene Delivery Improves Cardiac Structure and Function in a Murine Model of Diabetic Cardiomyopathy.

Diabetes is a major contributor to the increasing burden of heart failure prevalence globally, at least in part due to a disease process termed diabetic cardiomyopathy. Diabetic cardiomyopathy is characterised by cardiac structural changes that are caused by chronic exposure to the diabetic milieu. These structural changes are a major cause of left ventricular (LV) wall stiffness and the development of LV dysfunction. In the current study, we investigated the therapeutic potential of a cardiac-targeted bone morphogenetic protein 7 (BMP7) gene therapy, administered once diastolic dysfunction was present, mimicking the timeframe in which clinical management of the cardiomyopathy would likely be desired. Following 18 weeks of untreated diabetes, mice were administered with a single tail-vein injection of recombinant adeno-associated viral vector (AAV), containing the BMP7 gene, or null vector. Our data demonstrated, after 8 weeks of treatment, that rAAV6-BMP7 treatment exerted beneficial effects on LV functional and structural changes. Importantly, diabetes-induced LV dysfunction was significantly attenuated by a single administration of rAAV6-BMP7. This was associated with a reduction in cardiac fibrosis, cardiomyocyte hypertrophy and cardiomyocyte apoptosis. In conclusion, BMP7 gene therapy limited pathological remodelling in the diabetic heart, conferring an improvement in cardiac function. These findings provide insight for the potential development of treatment strategies urgently needed to delay or reverse LV pathological remodelling in the diabetic heart.

Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy.

People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range of diabetic complications and are a common feature of the diabetic heart. In this study, we sought to characterise impairments in mitochondrial structure and function in a recently described experimental mouse model of diabetic cardiomyopathy. Diabetes was induced in 6-week-old male FVB/N mice by the combination of three consecutive-daily injections of low-dose streptozotocin (STZ, each 55 mg/kg i.p.) and high-fat diet (42% fat from lipids) for 26 weeks. At study end, diabetic mice exhibited elevated blood glucose levels and impaired glucose tolerance, together with increases in both body weight gain and fat mass, replicating several aspects of human type 2 diabetes. The myocardial phenotype of diabetic mice included increased myocardial fibrosis and left ventricular (LV) diastolic dysfunction. Elevated LV superoxide levels were also evident. Diabetic mice exhibited a spectrum of LV mitochondrial changes, including decreased mitochondria area, increased levels of mitochondrial complex-III and complex-V protein abundance, and reduced complex-II oxygen consumption. In conclusion, these data suggest that the low-dose STZ-high fat experimental model replicates some of the mitochondrial changes seen in diabetes, and as such, this model may be useful to study treatments that target the mitochondria in diabetes.

Tunnelled peritoneal drainage catheter placement for the palliative management of refractory ascites in patients with liver cirrhosis.

OBJECTIVE: Refractory ascites is an established indication for liver transplantation. While transplantation is regarded as the definitive therapy for this condition, many patients are unsuitable due to comorbidity or frailty. Alternatives such as transjugular intrahepatic portosystemic shunt (TIPSS) and large-volume paracentesis can lead to complications, including encephalopathy, circulatory and renal dysfunction, and protein-calorie deficiency that may accelerate sarcopenia. Cost and complication rates limit therapies such as alfapump. While there are data to support the use of indwelling catheters in the management of patients with malignant ascites, there is limited evidence to support their routine use in the context of end-stage liver cirrhosis. Here we describe our centres' experience using indwelling tunnelled ascitic drains over a 6-year period. METHODS: A retrospective review of data (January 2012-May 2018) was undertaken for all patients with refractory ascites who underwent a tunnelled ascitic drain. Demographics, disease aetiology, procedure data and follow-up data were obtained through interrogation of electronic records and reports. RESULTS: Twenty-five drains were placed. All procedures were technically successful with no immediate complications. Six patients were readmitted following their index admission with abdominal pain and suspected infected ascites (although only two had a positive ascitic fluid culture). There were three cases of abdominal wall cellulitis and three of leakage around the tunnel site; all managed conservatively. CONCLUSION: Indwelling drains appear an effective strategy for palliative management of select patients with liver cirrhosis complicated by refractory ascites who are not amenable to undergo TIPSS or transplantation. While complications can occur, these are most usually minor and can be managed on an outpatient basis.