Expert Panel Consensus for Optimizing Outcomes in Neovascular Age-Related Macular Degeneration in the Context of Suboptimal Response to a Biosimilar: The Role of Aflibercept.

Purpose: The inclusion of ranibizumab biosimilars into National Health Service England commissioning recommendations published in 2022 created a need for expert guidance to optimize treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) who otherwise may not have received first-line ranibizumab. This article provides a consensus treatment pathway supporting timely identification and management of a suboptimal response to these therapies, thereby aiming to facilitate clinically meaningful outcomes and efficient management of service capacity under specific circumstances where ranibizumab biosimilars may be initiated as a first-line treatment.

Methods: Two structured round-table meetings of UK medical retina specialists were held in person and virtually on September 22 and November 3, 2022, respectively.

Smartphone-based machine learning model for real-time assessment of medical kidney biopsy.

Background: Kidney biopsy is the gold-standard for diagnosing medical renal diseases, but the accuracy of the diagnosis greatly depends on the quality of the biopsy specimen, particularly the amount of renal cortex obtained. Inadequate biopsies, characterized by insufficient cortex or predominant medulla, can lead to inconclusive or incorrect diagnoses, and repeat biopsy. Unfortunately, there has been a concerning increase in the rate of inadequate kidney biopsies, and not all medical centers have access to trained professionals who can assess biopsy adequacy in real time.

Inclusion of oil from transgenic Camelina sativa in feed effectively supplies EPA and DHA to Atlantic salmon (Salmo salar) grown to market size in seawater pens.

Atlantic salmon were fed either a diet reflecting current commercial feeds with added oil supplied by a blend of fish oil and rapeseed oil (COM), or a diet formulated with oil from transgenic Camelina sativa containing 20% EPA + DHA (TCO). Salmon were grown from smolt to market size (>3 kg) in sea pens under semi-commercial conditions. There were no differences in growth, feed efficiency or survival between fish fed the TCO or COM diets at the end of the trial.

Real-world service costs for neovascular-AMD clinics in the United Kingdom: structured literature review and scenario analysis.

Objective: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity).

Methods: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice.

Unstable Carotid Artery Thrombus in a Patient With COVID-19 Infection.

We present a case of an unvaccinated, 43-year-old African American female patient with COVID-19 infection and clinical evidence of a left hemispheric stroke. A non-occlusive thrombus with a radiographic target lesion was identified on computed tomography angiography (CTA). A multi-disciplinary discussion regarding concern for embolization was provided due to its unstable nature, as well as evidence of recent stroke.

Development and Validation of a Multiclass Model Defining Molecular Archetypes of Kidney Transplant Rejection: A Large Cohort Study of the Banff Human Organ Transplant Gene Expression Panel.

Gene expression profiling from formalin-fixed paraffin-embedded (FFPE) renal allograft biopsies is a promising approach for feasibly providing a molecular diagnosis of rejection. However, large-scale studies evaluating the performance of models using NanoString platform data to define molecular archetypes of rejection are lacking. We tested a diverse retrospective cohort of over 1400 FFPE biopsy specimens, rescored according to Banff 2019 criteria and representing 10 of 11 United Network of Organ Sharing regions, using the Banff Human Organ Transplant panel from NanoString and developed a multiclass model from the gene expression data to assign relative probabilities of 4 molecular archetypes: No Rejection, Antibody-Mediated Rejection, T Cell-Mediated Rejection, and Mixed Rejection.

Evolutionary Analyses of Gene Expression Divergence in Panicum hallii: Exploring Constitutive and Plastic Responses Using Reciprocal Transplants.

The evolution of gene expression is thought to be an important mechanism of local adaptation and ecological speciation. Gene expression divergence occurs through the evolution of cis- polymorphisms and through more widespread effects driven by trans-regulatory factors. Here, we explore expression and sequence divergence in a large sample of Panicum hallii accessions encompassing the species range using a reciprocal transplantation experiment.

Cementless tapered wedge stems in patients undergoing primary total hip arthroplasty with Dorr C bone-are complication risks increased?

Background: The use of cementless femoral stems in patients undergoing primary total hip arthroplasty (THA) with Dorr C bone remains controversial for fear of fracture or subsidence. Purpose of this multicenter study was to compare clinical outcomes and complications of THA using a tapered femoral prosthesis in patients with Dorr C bone versus Dorr A/B bone.

Methods: A total of 1,030 patients underwent primary THA with a tapered wedge femoral stem at a minimum one year follow up.

Hybrid Paraclavicular Decompression for Venous Thoracic Outlet Syndrome with Primary Endovascular Reconstruction.

Background: Venous thoracic outlet syndrome (vTOS) is characterized by severe stenosis and potential thrombosis of the axillary-subclavian vein (effort thrombosis) with significant effects on patient mobility, quality of life, and risks associated with possible anticoagulation. Treatment goals are aimed at symptomatic improvement and freedom from recurrent thrombosis. To date, there exist no clear protocols or recommendations on surgical approach that result in optimal outcomes.

Evaluation of care with intravitreal aflibercept treatment for UK patients with diabetic macular oedema: DRAKO study 24-month real-world outcomes.

Background/ Objectives: DRAKO (NCT02850263) was a 24-month, prospective, observational, multi-centre cohort study that enrolled patients diagnosed with diabetic macular oedema (DMO) including central involvement. The study aimed to evaluate standard of care intravitreal aflibercept (IVT-AFL) treatment in the UK. This analysis describes the 12-month outcomes for patients with prior anti-vascular endothelial growth factor (VEGF) treatment for DMO other than IVT-AFL (C2), and 2-year outcomes for both anti-VEGF treatment-naïve patients (C1) and C2 patients.

A point mutation in the kinase domain of CRK10 leads to xylem vessel collapse and activation of defence responses in Arabidopsis.

Cysteine-rich receptor-like kinases (CRKs) are a large family of plasma membrane-bound receptors ubiquitous in higher plants. However, despite their prominence, their biological roles have remained largely elusive so far. In this study we report the characterization of an Arabidopsis mutant named crk10-A397T in which alanine 397 has been replaced by a threonine in the αC helix of the kinase domain of CRK10, known to be a crucial regulatory module in mammalian kinases.

Use of Endoscopic Vein Harvest Yields Improved Outcomes in Popliteal Artery Aneurysm Repair.

Background: There is growing literature showing that endoscopic vein harvest (EVH) is safe, with excellent patency rates and decreased wound complications when treating infrainguinal occlusive disease. Our institution has performed EVH since 2003 with a dedicated team of providers specializing in endoscopic vein harvest. The purpose of this study was to evaluate major outcomes of EVH as an adjunct to standard, open operative repair of popliteal artery aneurysms.

Surgical placement of implantable cardiac loop recorders in great apes.

Cardiovascular disease is the leading cause of morbidity and mortality in zoologically managed adult great apes, accounting for 29%-77% of adult deaths in the North American population depending on the species. In an effort to better understand the underlying causes of heart disease, implantable loop recorders (ILRs) have been used in some cases to monitor great apes with suspected or known cases of arrhythmia. This is a 10-year review of the Great Ape Heart Project's experience of implanting 21 ILRs in 7 gorillas (Gorilla gorilla gorilla; 9 total ILR devices), 5 chimpanzees (Pan troglodytes, 11 total ILR devices), and 1 orangutan (Pongo abelii, 1 ILR device) in an effort to develop effective methods for surgical implantation and remote collection of the data for analysis.

Evaluation of standard-of-care intravitreal aflibercept treatment practices in patients with diabetic macular oedema in the UK: DRAKO study outcomes.

Background/objectives: DRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti-vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL.

Engineering plant-based feedstocks for sustainable aquaculture.

There is a growing recognition of the challenges associated with ensuring good nutrition for all without compromising the environment. This is particularly true for aquaculture, given the reliance on marine extraction for key feed ingredients, yet at the same time it delivers key nutrients such as omega-3 long chain polyunsaturated fatty acids. This review will consider progress in transitioning away from oceanic-derived fish oils as feed ingredients, focusing on the emerging transgenic plant sources of these fatty acids.

Ten-year experience of infrainguinal bypass with endoscopic vein harvest.

Objectives: There is conflicting data comparing minimally invasive vein harvest (MIVH) using endoscopic technique and open vein harvest (OVH) in terms of bypass patency, wound infection incidence, and patient morbidity. Our institution has performed MIVH since 2003 for peripheral bypass procedures with a consistent team of specialized endoscopic vein harvesters. This study reviewed the major outcomes of MIVH infrainguinal bypass at our institution given a predominant cohort of critical limb ischemia.

Gene-by-environment interactions in plants: Molecular mechanisms, environmental drivers, and adaptive plasticity.

Plants demonstrate a broad range of responses to environmental shifts. One of the most remarkable responses is plasticity, which is the ability of a single plant genotype to produce different phenotypes in response to environmental stimuli. As with all traits, the ability of plasticity to evolve depends on the presence of underlying genetic diversity within a population.

Light Chain-Only Immunotactoid Glomerulopathy: A Case Report.

The monotypic variant of immunotactoid glomerulopathy (ITG), strongly associated with low-grade lymphoproliferative disorders, is characterized histologically by glomerulonephritis and microtubular deposits of monoclonal immunoglobulin G (IgG). We report a patient with high-risk κ light chain multiple myeloma who presented with acute kidney injury, hematuria, proteinuria, and hypocomplementemia. Kidney biopsy revealed immunotactoid glomerulopathy concomitant with κ light chain myeloma cast nephropathy.

Using field evaluation and systematic iteration to rationalize the accumulation of omega-3 long-chain polyunsaturated fatty acids in transgenic Camelina sativa.

The Brassicaceae Camelina sativa (gold of pleasure) is now an established niche crop and being used as a transgenic host for a range of novel seed traits. Most notable of these is the accumulation of omega-3 long-chain polyunsaturates such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), fatty acids normally only found in marine organisms. As part of continued efforts to optimize the accumulation of these non-native fatty acids via seed-specific expression of algal genes, a new series of iterative constructs was built and introduced into Camelina.