Health equality, race and pharmacogenomics.

Pharmacogenomics is increasingly moving into mainstream clinical practice. Careful consideration must be paid to inclusion of diverse populations in research, translation and implementation, in the historical and social context of population stratification, to ensure that this leads to improvements in healthcare for all rather than increased health disparities. This review takes a broad and critical approach to the current role of diversity in pharmacogenomics and addresses potential pitfalls in order to raise awareness for prescribers.

Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA).

Background: Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors.

Percutaneous Achilles tenotomy under local anaesthetic in the clubfoot clinic was safe during the COVID-19 pandemic, for both children and parents.

Purpose: An Achilles tenotomy is routinely required to correct the equinus deformity in Congenital talipes equinovarus (CTEV) patients as part of the gold standard treatment using the Ponseti method. This procedure can be performed in clinic under local anaesthetic or in theatre under general anaesthetic. The COVID-19 pandemic reduced theatre capacity and caused a delay to CTEV patients' treatment.

Evaluation of Urinary Biomarkers of Proximal Tubular Injury, Inflammation, and Fibrosis in Patients With Albuminuric and Nonalbuminuric Diabetic Kidney Disease.

Introduction: Albuminuric and nonalbuminuric pathways contribute to diabetic kidney disease. Proximal tubule and inflammation play important roles in these processes. Urinary biomarker(s) to detect early kidney damage and predict progression are needed.

High glucose-induced Smad3 linker phosphorylation and CCN2 expression are inhibited by dapagliflozin in a diabetic tubule epithelial cell model.

Background: In the kidney glucose is freely filtered by the glomerulus and, mainly, reabsorbed by sodium glucose cotransporter 2 (SGLT2) expressed in the early proximal tubule. Human proximal tubule epithelial cells (PTECs) undergo pathological and fibrotic changes seen in diabetic kidney disease (DKD) in response to elevated glucose. We developed a specific in vitro model of DKD using primary human PTECs with exposure to high D-glucose and TGF-β1 and propose a role for SGLT2 inhibition in regulating fibrosis.

Infective endocarditis in paediatric population.

Infective endocarditis is very uncommon in children; however, when it does arise, it can lead to severe consequences. The biggest risk factor for paediatric infective endocarditis today is underlying congenital heart defects. The most common causative organisms are Staphylococcus aureus and the viridans group of streptococci.

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers.

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays.

Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection.

The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4 T cell responses with strong interleukin (IL)-2 cytokine expression.

Co-designing organisational improvements and interventions to increase inpatient activity in four stroke units in England: a mixed-methods process evaluation using normalisation process theory.

Objective: To explore facilitators and barriers to using experience-based co-design (EBCD) and accelerated EBCD (AEBCD) in the development and implementation of interventions to increase activity opportunities for inpatient stroke survivors.

Design: Mixed-methods process evaluation underpinned by normalisation process theory (NPT).

Setting: Four post-acute rehabilitation stroke units in England.

Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation.

Objectives: This study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF).

Background: LAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF.

The PRICES statement: an ESICM expert consensus on methodology for conducting and reporting critical care echocardiography research studies.

Purpose: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies.

The pathophysiology of functional movement disorders.

Functional neurological disorder is characterized by neurological symptoms that cannot be explained by typical neurological diseases or other medical conditions. This review will critically discuss the literature on the pathophysiology of functional movement disorders (FMD), including functional neuroimaging studies, neurophysiological studies, studies on biomarkers and genetic studies. According to PRISMA guidelines for systematic reviews, we selected 39 studies.

Renal Manifestations of Tuberous Sclerosis Complex: Key Findings From the Final Analysis of the TOSCA Study Focussing Mainly on Renal Angiomyolipomas.

Renal angiomyolipomas are one of the most common renal manifestations in patients with tuberous sclerosis complex (TSC), with potentially life-threatening complications and a poor prognosis. Despite the considerable progress in understanding TSC-associated renal angiomyolipomas, there are no large scale real-world data. The aim of our present study was to describe in detail the prevalence and outcome of renal angiomyolipomas in patients with TSC, enrolled into the TuberOus SClerosis registry to increase disease Awareness (TOSCA) from 170 sites across 31 countries worldwide.

Derepression of glomerular filtration, renal blood flow and antioxidant defence in patients with type 2 diabetes at high-risk of cardiorenal disease.

Background: The role of antioxidant status on microvascular blood flow and glomerular filtration (eGFR) in patients with type 2 diabetes and hypertension whose risk of progressive renal disease varies by ethnicity is unknown.

Methods: Adult, non-Caucasian (n = 101) and Caucasian (n = 69) patients with type 2 diabetes, hypertension and/or microalbuminuria and an eGFR > 45 mL/min/1.73 m were randomised to receive 400 IU vitamin E and/or 20 μg selenium daily or matching placebo.

Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study.

Research on tuberous sclerosis complex (TSC) to date has focused mainly on the physical manifestations of the disease. In contrast, the psychosocial impact of TSC has received far less attention. The aim of this study was therefore to examine the impact of TSC on health, quality of life (QoL), and psychosocial well-being of individuals with TSC and their families.

Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project.

Background: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries.

The experiences of individuals with cervical spinal cord injury and their family during post-injury care in non-specialised and specialised units in UK.

Background: Individuals with acute cervical spinal cord injury require specialised interventions to ensure optimal clinical outcomes especially for respiratory, swallowing and communication impairments. This study explores the experiences of post-injury care for individuals with cervical spinal cord injury and their family members during admissions in specialised and non-specialised units in the United Kingdom.

Methods: Semi-structured interviews were undertaken with individuals with a cervical spinal cord injury and their family member, focussing on the experience of care across units.

Tuberous Sclerosis Complex-Associated Neuropsychiatric Disorders (TAND): New Findings on Age, Sex, and Genotype in Relation to Intellectual Phenotype.

Knowledge is increasing about TSC-Associated Neuropsychiatric Disorders (TAND), but little is known about the potentially confounding effects of intellectual ability (IA) on the rates of TAND across age, sex, and genotype. We evaluated TAND in (a) children vs. adults, (b) males vs.

Effect of Gemcitabine based chemotherapy on the immunogenicity of pancreatic tumour cells and T-cells.

Purpose: Chemotherapy for advanced pancreatic cancer has limited efficacy due to the difficultly of treating established tumours and the evolution of tumour resistance. Chemotherapies for pancreatic cancer are typically studied for their cytotoxic properties rather than for their ability to increase the immunogenicity of pancreatic tumour cells. In this study Gemcitabine in combination with immune modulatory chemotherapies Oxaliplatin, zoledronic acid and pomalidomide was studied to determine how combination therapy alters the immunogenicity of pancreatic tumour cell lines and subsequent T-cell responses.

The use of technology in the subcategorisation of osteoarthritis: a Delphi study approach.

Objective: This UK-wide OATech Network + consensus study utilised a Delphi approach to discern levels of awareness across an expert panel regarding the role of existing and novel technologies in osteoarthritis research. To direct future cross-disciplinary research it aimed to identify which could be adopted to subcategorise patients with osteoarthritis (OA).

Design: An online questionnaire was formulated based on technologies which might aid OA research and subcategorisation.