Longitudinal associations of retinal vessel morphology with intraocular pressure and blood pressure at follow-up visit-Findings from a Danish eye and vision cohort, Project FOREVER.

PURPOSE: To characterise the retinal vasculometry of a Danish eye and vision cohort and examine associations with systolic blood pressure (BP), diastolic BP, mean arterial BP, and intraocular pressure (IOP). DESIGN: Longitudinal study. METHODS: The retinal vasculature of fundus images from the FOREVER (Finding Ophthalmic Risks and Evaluating the Value of Eye exams and their predictive Reliability) cohort was analysed using a fully automated image analysis program. Longitudinal associations of retinal vessel morphology at follow-up visit with IOP (baseline and follow-up) and BP (follow-up) were examined using multilevel linear regression models adjusting for age, sex and retinal vasculometry at baseline as fixed effects and person as random effect. Width measurements were additionally adjusted for the spherical equivalent. RESULTS: A total of 2089 subjects (62% female) with a mean age of 61 (standard deviation 8) years and a mean follow-up period of 4.1 years (SD 0.6 years) were included. The mean arteriolar diameter was approximately 20% thinner than the mean venular diameter, and venules were about 21%-23% less tortuous than arterioles. BP at follow-up was associated with decreased arteriolar diameter from baseline to follow-up. After adjusting for baseline IOP, IOP at follow-up was associated with increased arteriolar tortuosity above baseline (0.59%, 95% CI 0.08-1.10, p-value 0.024). CONCLUSION: In a Danish eye and vision cohort, variations in BP and alterations in IOP over time were associated with changes in the width and tortuosity of retinal vessels. Our findings contribute novel insights into retinal vascular alterations over time

Comparison of mortality in people with type 2 diabetes between different ethnic groups: Systematic review and meta-analysis of longitudinal studies.

AIMS: Type 2 diabetes (T2D) is more common in certain ethnic groups. This systematic review compares mortality risk between people with T2D from different ethnic groups and includes recent larger studies. METHODS: We searched nine databases using PRISMA guidelines (PROSPERO CRD42022372542). We included community-based prospective studies among adults with T2D from at least two different ethnicities. Two independent reviewers undertook screening, data extraction and quality assessment using the Newcastle-Ottawa Scale. The primary outcome compared all-cause mortality rates between ethnic groups (hazard ratio (HR) with 95% confidence intervals). RESULTS: From 30,825 searched records, we included 13 studies (7 meta-analysed), incorporating 573,173 T2D participants; 12 were good quality. Mortality risk was lower amongst people with T2D from South Asian [HR 0.68 (0.65-0.72)], Black [HR 0.82 (0.77-0.87)] and Chinese [HR 0.57 (0.46-0.70)] ethnicity compared to people of White ethnicity. Narrative synthesis corroborated these findings but demonstrated that people of indigenous Māori ethnicity had greater mortality risk compared to European ethnicity. CONCLUSIONS: People with T2D of South Asian, Black and Chinese ethnicity have lower all-cause mortality risk than White ethnicity, with Māori ethnicity having higher mortality risk. Factors explaining mortality differences require further study, including understanding complication risk by ethnicity, to improve diabetes outcomes

Do mental and physical health trajectories change around transitions into sandwich care? Results from the UK household longitudinal study.

OBJECTIVES: Sandwich carers provide care to ageing parents or older relatives while simultaneously raising dependent children. There has been little focus on how mental and physical health trajectories change around becoming a sandwich carer - a gap this study aims to fill. STUDY DESIGN: Prospective longitudinal study. METHODS: We used 10 waves of data from the UK Household Longitudinal Study (2009-2020) - a high-quality longitudinal data. Sandwich carers were parents who lived with children under age 16 and took up unpaid care of a family member in the older generation. Sandwich carers were matched with parents who did not take up any adult care (i.e., non-sandwiched parents) with similar characteristics. We then employed piecewise growth curve modelling to model the trajectories in mental and physical health before, during and after becoming a sandwich carer and comparing these with non-sandwiched parents. RESULTS: Among parents, the uptake of caring for a family member was associated with a deterioration in mental health, especially for those who spent more than 20 h per week caring for a family member. The deterioration persisted for several years. Those who cared intensively also experienced greater physical health declines during the transition. We did not see evidence of gender difference in the above associations. CONCLUSIONS: It is essential for society to recognise the unique needs and challenges of sandwich carers and provide them with the necessary support systems, resources, and community networks to ensure their health is maintained. Targeted support is required for sandwich carers who care intensively

Single-cycle parainfluenza virus type 5 vectors for producing recombinant proteins, including a humanized anti-V5 tag antibody.

Parainfluenza virus type 5 (PIV5) can cause either persistent or acute/lytic infections in a wide range of mammalian tissue culture cells. Here, we have generated PIV5 fusion (F)-expressing helper cell lines that support the replication of F-deleted viruses. As proof of the principle that F-deleted single-cycle infectious viruses can be used as safe and efficient expression vectors, we have cloned and expressed a humanized (Hu) version of the mouse anti-V5 tag antibody (clone SV5-Pk1). We show that multiple different cell lines can be infected and express high levels of the Hu anti-V5 antibody, with Chinese hamster ovary cells expressing 20-50 mg l-1 after 5 days when cells were grown to a density of ~1×106 cells per millilitre at the time of infection. We suggest that PIV5-based vectors may be further developed to produce recombinant proteins both in vitro and in vivo

Acute Kidney Injury in Acute Heart Failure - When to worry and when not to worry?

Acute kidney injury is common in patients with acute decompensated heart failure. It is more common in patients with acute heart failure who suffer from chronic kidney disease. Worsening renal function is often defined as a rise in serum creatinine of more than 0.3 milligrams per deciliter (26.5 µmol/L), which by definition, is acute kidney injury stage one. Perhaps the term acute kidney injury is more appropriate than worsening renal function as it is used universally by nephrologists, internists, and other medical practitioners. In health, the heart and the kidney support each other to maintain body's homeostasis. In disease, the heart and the kidney can adversely affect each other's function causing further clinical deterioration. In patients presenting with acute heart failure and fluid overload, therapy with diuretics for decongestion often causes a rise in serum creatinine and acute kidney injury. However, in the longer term the decongestion improves survival and prevents hospital admissions despite rising serum creatinine and acute kidney injury. It is important to realize that renal venous congestion due to increased right sided heart pressures in acute heart failure is a major cause of kidney dysfunction and hence decongestion therapy improves kidney function in the longer term. This review provides a perspective on the acceptable acute kidney injury with decongestion therapy which is associated with improved survival; as opposed to acute kidney injury due to tubular injury related to sepsis or nephrotoxic drugs, which is associated with poor survival

Iron management and exercise training in individuals with chronic kidney disease: lived experiences.

BACKGROUND: Non-anaemic iron deficiency is highly prevalent in people living with chronic kidney disease (CKD) but is underdiagnosed and undertreated, especially in earlier stages of CKD. A multicentre trial assessing the effect of intravenous iron supplementation in iron-deficiency but not anaemic people with CKD included a qualitative sub-study that aimed to explore the patient experience and psychosocial impact of living with CKD and iron deficiency, and the experience of the therapeutic intervention (intravenous iron and exercise). METHODS: Semi-structured interviews were conducted with 23 trial participants blinded to treatment. Topics explored included experiences of living with CKD and iron deficiency, symptoms, social and leisure activities, quality of life, and participants' views and experiences of receiving the therapeutic intervention. Thematic analysis was used to identify and report themes. RESULTS: Six overarching themes were identified: lack of awareness of iron deficiency; overwhelming feelings of tiredness; feeling limited; balancing emotions; perceptions and experiences of therapeutic treatment received; and impact of trial participation on life participation. Trial participation, specifically the exercise training, was perceived to be beneficial, with improvements in life participation and psychological wellbeing experienced. However, there were no clear differences between treatment groups, with mixed perceptions about which therapeutic treatment was received. CONCLUSIONS: The impact of tiredness on individuals with CKD is profound and can result in reduced vitality, impaired ability to engage in life activities and emotional conflict. Improved communication and support about psychosocial impact and management of symptoms, particularly fatigue, for people with CKD may be required, alongside effective therapeutic interventions, to improve symptom management and quality of life

Evaluation of the analytical and clinical performance of a high-sensitivity troponin I point-of-care assay in the Mersey Acute Coronary Syndrome Rule Out Study (MACROS-2).

OBJECTIVES: The objective of this study is to evaluate the analytical and diagnostic performance of a high-sensitivity point-of-care (POC) cardiac troponin I assay, the Quidel TriageTrue™ (QuidelOrtho Inc, San Diego, USA), compared to central laboratory testing (CLT) in accelerated diagnostic protocols (ADP) in real time in a clinical environment. METHODS: In a nested sub-study of a pragmatic randomised control trial, consecutive patients with suspected acute coronary syndrome (ACS) and chest pain 50 % lower than 99th percentile [20.5 ng/L]) and a 20 % CV at 1.2 ng/L. Receiver operator characteristics (ROC) curves were computed for each assay against adjudicated index type 1 MI to study clinical performance. At all-time points there were excellent performance for whole blood POC TriageTrue: area under the curve (AUC) 0.97 [95 % CI 0.94-098], 0.98 [95 % CI 0.97-1.00] and 0.95 [95 % CI 0.92-0.98] at time 0, 1 and 3 h respectively. There was statistical equivalence for performance of whole blood and plasma POC TriageTrue hs-TnI and laboratory Siemens Atellica hs-TnI. CONCLUSIONS: The whole blood POC TriageTrue hs-TnI assay demonstrates imprecision levels consistent with high sensitivity characteristics and has a clinical performance equivalent to an established, validated and NICE approved laboratory Siemens Atellica hs-TnI

Personalized Heart Digital Twins Detect Substrate Abnormalities in Scar-Dependent Ventricular Tachycardia.

BACKGROUND: Current outcomes from catheter ablation for scar-dependent ventricular tachycardia (VT) are limited by high recurrence rates and long procedure durations. Personalized heart digital twin technology presents a noninvasive method of predicting critical substrate in VT, and its integration into clinical VT ablation offers a promising solution. The accuracy of the predictions of digital twins to detect invasive substrate abnormalities is unknown. We present the first prospective analysis of digital twin technology in predicting critical substrate abnormalities in VT. METHODS: Heart digital twin models were created from 18 patients with scar-dependent VT undergoing catheter ablation. Contrast-enhanced cardiac magnetic resonance images were used to reconstruct finite-element meshes, onto which regional electrophysiological properties were applied. Rapid-pacing protocols were used to induce VTs and to define the VT circuits. Predicted optimum ablation sites to terminate all VTs in the models were identified. Invasive substrate mapping was performed, and the digital twins were merged with the electroanatomical map. Electrogram abnormalities and regions of conduction slowing were compared between digital twin-predicted sites and nonpredicted areas. RESULTS: Electrogram abnormalities were significantly more frequent in digital twin-predicted sites compared with nonpredicted sites (468/1029 [45.5%] versus 519/1611 [32.2%]; P<0.001). Electrogram duration was longer at predicted sites compared with nonpredicted sites (82.0±25.9 milliseconds versus 69.7±22.3 milliseconds; P<0.001). Digital twins correctly identified 21 of 26 (80.8%) deceleration zones seen on isochronal late activation mapping. CONCLUSIONS: Digital twin-predicted sites display a higher prevalence of abnormal and prolonged electrograms compared with nonpredicted sites and accurately identify regions of conduction slowing. Digital twin technology may help improve substrate-based VT ablation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04632394

Current management of chronic kidney disease in type-2 diabetes-A tiered approach: An overview of the joint Association of British Clinical Diabetologists and UK Kidney association (ABCD-UKKA) guidelines.

A growing and significant number of people with diabetes develop chronic kidney disease (CKD). Diabetes-related CKD is a leading cause of end-stage kidney disease (ESKD) and people with diabetes and CKD have high morbidity and mortality, predominantly related to cardiovascular disease (CVD). Despite advances in care over the recent decades, most people with CKD and type 2 diabetes are likely to die of CVD before developing ESKD. Hyperglycaemia and hypertension are modifiable risk factors to prevent onset and progression of CKD and related CVD. People with type 2 diabetes often have dyslipidaemia and CKD per se is an independent risk factor for CVD, therefore people with CKD and type 2 diabetes require intensive lipid lowering to reduce burden of CVD. Recent clinical trials of people with type 2 diabetes and CKD have demonstrated a reduction in composite kidney end point events (significant decline in kidney function, need for kidney replacement therapy and kidney death) with sodium-glucose co-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonist finerenone and glucagon-like peptide 1 receptor agonists. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have previously undertaken a narrative review and critical appraisal of the available evidence to inform clinical practice guidelines for the management of hyperglycaemia, hyperlipidaemia and hypertension in adults with type 2 diabetes and CKD. This 2024 abbreviated updated guidance summarises the recommendations and the implications for clinical practice for healthcare professionals who treat people with diabetes and CKD in primary, community and secondary care settings