Elevated serum vitamin B12 concentrations in a patient with pancreatic exocrine insufficiency.

This case describes a patient with pancreatic exocrine insufficiency and persistently elevated serum vitamin B12 concentrations that were not due to supplementation or associated with hepatic or hematological pathology. Laboratory investigations suggested the presence of macro-B12 as the cause of this patient's raised serum vitamin B12. Macro-B12 is often formed when vitamin B12-vitamin binding proteins (transcobalamin and haptocorrin) complex with immunoglobulins.

2024 White Paper on Recent Issues in Bioanalysis: Evolution of Immunogenicity Assessment beyond ADA/NAb; Regulated Genomic/NGS Assays; Hypersensitivity Reactions; Minimum Noise Reduction; False Positive Range; Modernized Vaccine Approaches; NAb/TAb Correlation - Recommendations on Advanced Strategies for Molecular Assays and Immunogenicity of Gene Therapy, Cell Therapy, Vaccine; Biotherapeutics Immunogenicity Assessment & Clinical Relevance - Regulatory Agencies' Input on Immunogenicity/Technologies of Biotherapeutics, Gene, Cell & Vaccine Therapies).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

NHS-Galleri trial: Enriched enrolment approaches and sociodemographic characteristics of enrolled participants.

Background/aims: Certain sociodemographic groups are routinely underrepresented in clinical trials, limiting generalisability. Here, we describe the extent to which enriched enrolment approaches yielded a diverse trial population enriched for older age in a randomised controlled trial of a blood-based multi-cancer early detection test (NCT05611632).

Methods: Participants aged 50-77 years were recruited from eight Cancer Alliance regions in England.

2024 White paper on recent issues in bioanalysis: Impact of LDT in US and IVDR in EU; AI/ML for High Parameter Flow Cytometry; The rise of Olink Technology; CDx for AAV Gene Therapies; Integrative Bioanalysis by Multiple Platforms; Super Sensitive ADA/NAb LBA ( - Recommendations on Advanced Strategies for Biomarkers, IVD/CDx Assays (BAV), Cell Based Assays (CBA), and Ligand-Binding Assays (LBA) - Regulatory Agencies' Input on Biomarkers, IVD/CDx, and Biomarker Assay Validation).

The 18th Workshop on Recent Issues in Bioanalysis (18th WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Hyperactivity and Pro-inflammatory Functions of Platelets in Diabetes.

Cardiovascular complications claim the lives of up to 70% of patients with diabetes mellitus (DM). The mechanisms increasing cardiovascular risk in DM remain to be fully understood and successfully addressed. Nonetheless, there is increasing evidence in the scientific literature of the participation of platelets in the cardiovascular complications of DM.

The Impact of Modifiable Risk Factors on the Endothelial Cell Methylome and Cardiovascular Disease Development.

Cardiovascular disease (CVD) is the most prevalent cause of mortality and morbidity in the Western world. A common underlying hallmark of CVD is the plaque-associated arterial thickening, termed atherosclerosis. Although the molecular mechanisms underlying the aetiology of atherosclerosis remain unknown, it is clear that both its development and progression are associated with significant changes in the pattern of DNA methylation within the vascular cell wall.

Organizational Initiatives for the Recruitment, Retention and Advancement of Black Nurses: A Rapid Review.

Introduction: Black nurses are under-represented in the Canadian nursing workforce. A legacy of discrimination and systemic barriers reinforce the under-representation of Black nurses in the nursing workforce throughout the health system.

Objective: The objective of this study was to identify and describe organizational initiatives for the recruitment, retention and advancement of Black nurses in the healthcare system.

Differences in Brain Volume and Thickness between Shammah (Smokeless Tobacco) Users and Non-Users: A Cross-Sectional Study.

Previous research has shown that smoking tobacco is associated with changes or differences in brain volume and cortical thickness, resulting in a smaller brain volume and decreased cortical thickness in smokers compared with non-smokers. However, the effects of smokeless tobacco on brain volume and cortical thickness remain unclear. This study aimed to investigate whether the use of shammah, a nicotine-containing smokeless tobacco popular in Middle Eastern countries, is associated with differences in brain volume and thickness compared with non-users and to assess the influence of shammah quantity and type on these effects.

Addressing the Environmental Impact of Pharmaceuticals: A Call to Action.

The contribution of health care to environmental and climate crises is significant, under-addressed, and with consequences for human health. This editorial is a call to action. Focusing on pharmaceuticals as a major environmental threat, we examine pharmaceutical impacts across their lifecycle, summarising greenhouse gas emissions, pollution, and biodiversity loss, and outlining challenges and opportunities to reduce this impact.

Glucagon-Like Peptide-1 Receptor Agonists in the Peri-Operative Period.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are emerging as an important class of drugs in the management of Type 2 Diabetes Mellitus (T2DM) and obesity. There are rising concerns of pulmonary aspiration with these medications due to drug-induced gastroparesis. While definitive association is uncertain, it is essential to be prudent and manage these patients as per the current evidence and recommendations.

How Outcome Prediction Could Aid Clinical Practice.

Predictive algorithms have myriad potential clinical decision-making implications from prognostic counselling to improving clinical trial efficiency. Large observational (or "real world") cohorts are a common data source for the development and evaluation of such tools. There is significant optimism regarding the benefits and use cases for risk-based care, but there is a notable disparity between the volume of clinical prediction models published and implementation into healthcare systems that drive and realise patient benefit.

Should All Doctors Undergo Mandatory Life Support Training?

Advanced life support certification has traditionally been the gold standard of resuscitation training for doctors and has been shown to improve outcomes from cardiac arrest. In 2021, Health Education England removed named courses from mandatory Foundational Programme competencies, which has resulted in capping of reimbursement and reduced access to courses. This represents a drop in educational standards which is particularly concerning when the medical school curriculum has been shown to deliver inconsistent, poor-quality resuscitation training.

Risk Assessment Prior to Cardiotoxic Anticancer Therapies in 7 Steps.

The burdens of cardiovascular (CV) diseases and cardiotoxic side effects of cancer treatment in oncology patients are increasing in parallel. The European Society of Cardiology (ESC) 2022 Cardio-Oncology guidelines recommend the use of standardized risk stratification tools to determine the risk of cardiotoxicity associated with different anticancer treatment modalities and the severity of their complications. The use of the Heart Failure Association-International Cardio-Oncology Society (HFA-ICOS) is essential for assessing risk prior to starting cancer treatment, and validation of these methods has been performed in patients receiving anthracyclines, human epidermal receptor 2 (HER2)-targeted therapies and breakpoint cluster region-abelson oncogene locus (BCR-ABL) inhibitors.

Delayed Diagnosis of Dysphagia: Consider "FOSMN".

An 80-year-old lady had a history of progressive swallowing difficulty over several years with significant weight loss, but prior investigations in several medical departments proved negative. Neurological assessment noted her complaint of impaired feeling for food in her mouth and examination showed impaired corneal reflexes and facial sensory function. Blink reflex electrodiagnostic testing was consistent with a diagnosis of facial onset sensory and motor neuronopathy (FOSMN).

Management of SGLT-2 Inhibitors in the Perioperative Period: Withhold or Continue?

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are commonly prescribed in diabetes mellitus and increasingly for cardiorenal protection. They carry the risk of euglycaemic diabetic ketoacidosis (eDKA). Guidelines around the perioperative handling of these medications are limited and some evidence suggests that withholding them can lead to more surgical complications and poorer glycaemic control.

How to Manage an Individual Living with Parkinson's Disease Who Acutely Cannot Swallow.

Parkinson's disease (PD) is a common neurodegenerative condition that can lead to problems swallowing. Individuals living with PD may be unable to take medications orally for various reasons including acute or chronic dysphagia, non-PD related causes and being placed nil-by-mouth for elective reasons. This article outlines a five-step approach to managing an individual living with PD who is unable to take oral medication acutely.

Once-Weekly Insulin: A Breakthrough in Diabetes Management or an Unresolved Challenge?

The advent of once-weekly insulin icodec is a promising development in the care of individuals with diabetes. These once-weekly formulations aimed to improve patient adherence and quality of life for patients who find daily injection administration challenging. Insulin icodec has demonstrated comparable glycemic control to conventionally used daily basal insulins, such as insulin glargine and degludec, in the ONWARDS clinical trials.

Finerenone: Do We Really Need an Additional Therapy in Type 2 Diabetes Mellitus and Kidney Disease?

Patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) face considerable cardiorenal morbidity and mortality despite existing therapies. Recent clinical trials demonstrate the efficacy of finerenone, a novel non-steroidal mineralocorticoid receptor antagonist, in reducing adverse renal and cardiovascular outcomes. This editorial briefly reviews the evidence and its implications for clinical practice, advocating the use of finerenone in these high-risk patients in combination with currently established treatment agents.

Prediction of Survival Outcomes in Patients with Glioma Using Magnetic Resonance Imaging (MRI): A Systematic Review and Meta-Analysis.

Background: Glioma is the most common malignancy in the central nervous system. Even with optimal therapies, glioblastoma (the most aggressive form of glioma) is incurable, with only 26.5% of patients having a 2-year survival rate.

Socio-economic inequalities in second primary cancer incidence: A competing risks analysis of women with breast cancer in England between 2000 and 2018.

We aimed to investigate socio-economic inequalities in second primary cancer (SPC) incidence among breast cancer survivors. Using Data from cancer registries in England, we included all women diagnosed with a first primary breast cancer (PBC) between 2000 and 2018 and aged between 18 and 99 years and followed them up from 6 months after the PBC diagnosis until a SPC event, death, or right censoring, whichever came first. We used flexible parametric survival models adjusting for age and year of PBC diagnosis, ethnicity, PBC tumour stage, comorbidity, and PBC treatments to model the cause-specific hazards of SPC incidence and death according to income deprivation, and then estimated standardised cumulative incidences of SPC by deprivation, taking death as the competing event.

Measuring the effect of RFID and marker recognition tags on cockroach (Blattodea: Blaberidae) behavior using AI-aided tracking.

Radio frequency identification (RFID) technology and marker recognition algorithms can offer an efficient and non-intrusive means of tracking animal positions. As such, they have become important tools for invertebrate behavioral research. Both approaches require fixing a tag or marker to the study organism, and so it is useful to quantify the effects such procedures have on behavior before proceeding with further research.

Circulating neuropeptide Y dynamics and performance during exercise in heart failure patients with contemporary medical and device therapy.

High cardiac sympathetic drive and release of the sympathetic cotransmitter neuropeptide Y (NPY) are significant features of congestive heart failure (CHF), in which resting venous NPY levels are known to be associated with mortality. However, whether circulating NPY levels increase during exercise in CHF when they are already elevated is controversial. We sought to establish the dynamics of circulating NPY levels in CHF patients treated with contemporary medical therapy and devices in relationship to indices of performance linked to long-term prognosis.

The ins and outs of liver fat metabolism: The effect of phenotype and diet on risk of intrahepatic triglyceride accumulation.

In health, the liver is a metabolically flexible organ that plays a key role in regulating systemic lipid and glucose concentrations. There is a constant flux of fatty acids (FAs) to the liver from multiple sources, including adipose tissue, dietary, endogenously synthesized from non-lipid precursors, intrahepatic lipid droplets and recycling of triglyceride-rich remnants. Within the liver, FAs are used for triglyceride synthesis, which can be oxidized, stored or secreted in very low-density lipoproteins into the systemic circulation.