Transient Ischaemic Attack in a Patient With Conn Syndrome: A Case Report and Literature Review on the Importance of Identifying Secondary Hypertension

BACKGROUND/AIM: Transient ischaemic attack (TIA) is characterised by a temporary neurological dysfunction resulting from focal ischaemia in the brain, spinal cord or retina without acute infarction. These episodes typically last less than 24 hours and are significant predictors of subsequent ischaemic strokes. Hypertension is a major risk factor for cerebrovascular events, and primary aldosteronism (PA) is recognised as a common cause of secondary hypertension. This case report presents a male patient with secondary hypertension due to Conn Syndrome, a form of PA, who experienced a TIA manifesting as left leg weakness, underscoring the heightened stroke risk associated with secondary hypertension. CASE REPORT: A 78-year-old male with secondary hypertension caused by Conn Syndrome presented with an episode of left leg weakness that resolved within 24 hours. After ruling out other potential causes such as metabolic disturbances, infections, and structural brain lesions, he was diagnosed with TIA and treated with dual antiplatelet therapy. A carotid ultrasound revealed significant stenosis, leading to a referral for carotid endarterectomy. Long-term management included clopidogrel monotherapy and optimising hypertension control. CONCLUSION: This case highlights the increased stroke risk in patients with Conn Syndrome-related hypertension, emphasising the importance of early recognition and optimising hypertension management in patients with secondary hypertension to prevent future cerebrovascular events.This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international licenseRDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Comprehensive clinical and molecular characterization with long-term outcomes in 40 patients with congenital hyperinsulinism

PURPOSE: Congenital hyperinsulinism (CHI) represents the most frequent cause of recurrent hypoglycemia in neonates and infants, stemming from defects in the regulatory pathways of insulin secretion from pancreatic beta cells. This study aims to assess the clinical and genetic characteristics of a CHI cohort and to discuss the complexities involved in managing this heterogeneous disorder. METHODS: Forty patients (23 girls) with CHI were included in the study. Data on the diagnosis and treatment of CHI were obtained from the medical records. RESULTS: The median age at diagnosis was 1.4 months (range 0.1-30 months). The mean gestational age was 37.8 ± 2.4 weeks, and the birth weight was 1.1 ± 2.0 SDS. The consanguinity ratio was 35.0%. Median glucose, insulin, and C-peptide concentrations at diagnosis were 34.0 mg/dl (IQR 25.2-41.7), 12.4µU/ml (IQR 4.4-27.1), and 1.5 ng/ml (IQR 0.7-3.8), respectively. Molecular genetic diagnosis could be established in 62.5% (n = 25). Pathogenic variants were predominantly identified in the KATP channel genes (17/25, 68%), with the ABCC8 being the most frequent (n = 15; biallelic: 8, monoallelic: 7). KCNJ11 variants were identified in two (5.0%), GLUD1 variants in three (7.5%), and HADH variants in five patients (12.5%). Pancreatectomy was performed in 10 patients, with a mean age at the time of surgery of 3.9 ± 3.2 months. The genetic etiology was identified in all patients who underwent pancreatectomy, all of whom had defects in the KATP channel. ABCC8 variants were detected in nine (biallelic: 5, monoallelic: 4), while a biallelic variant in the KCNJ11 was identified in one case. CONCLUSION: A molecular genetic diagnosis was identified in approximately two-thirds of our cohort, underscoring the significance of genetic testing in the management of CHI. Ongoing advances in genetic technologies are anticipated to enhance our understanding of the etiopathogenesis of CHI and support the development of more personalized therapeutic strategies. Although the genotype-phenotype correlation remains only partially elucidated, specific genetic variants may provide predictive insights into treatment resistance, thereby informing more targeted treatment approaches.None (all rights reserved under exclusive licence to Springer Nature

Genetic constraint at single amino acid resolution in protein domains improves missense variant prioritisation and gene discovery

BACKGROUND: One of the major hurdles in clinical genetics is interpreting the clinical consequences associated with germline missense variants in humans. Recent significant advances have leveraged natural variation observed in large-scale human populations to uncover genes or genomic regions that show a depletion of natural variation, indicative of selection pressure. We refer to this as genetic constraint". Although existing genetic constraint metrics have been demonstrated to be successful in prioritising genes or genomic regions associated with diseases, their spatial resolution is limited in distinguishing pathogenic variants from benign variants within genes. METHODS: We aim to identify missense variants that are significantly depleted in the general human population. Given the size of currently available human populations with exome or genome sequencing data, it is not possible to directly detect depletion of individual missense variants, since the average expected number of observations of a variant at most positions is less than one. We instead focus on protein domains, grouping homologous variants with similar functional impacts to examine the depletion of natural variations within these comparable sets. To accomplish this, we develop the Homologous Missense Constraint (HMC) score. We utilise the Genome Aggregation Database (gnomAD) 125 K exome sequencing data and evaluate genetic constraint at quasi amino-acid resolution by combining signals across protein homologues. RESULTS: We identify one million possible missense variants under strong negative selection within protein domains. Though our approach annotates only protein domains, it nonetheless allows us to assess 22% of the exome confidently. It precisely distinguishes pathogenic variants from benign variants for both early-onset and adult-onset disorders. It outperforms existing constraint metrics and pathogenicity meta-predictors in prioritising de novo mutations from probands with developmental disorders (DD). It is also methodologically independent of these, adding power to predict variant pathogenicity when used in combination. We demonstrate utility for gene discovery by identifying seven genes newly significantly associated with DD that could act through an altered-function mechanism. CONCLUSIONS: Grouping variants of comparable functional impacts is effective in evaluating their genetic constraint. HMC is a novel and accurate predictor of missense consequence for improved variant interpretation."Published version, accepted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

The discontinuation of implantable cardioverter defibrillator shock therapies towards the end of life: consensus guideline from the British Heart Rhythm Society

Implantable cardioverter defibrillators (ICDs) are implanted in increasing numbers of patients with the aim of treating ventricular arrhythmias in high-risk patients and reducing their risk of dying. Individuals are also living longer with these devices. As a result, a greater number of patients with an ICD will deteriorate either with worsening cardiac failure, another non-cardiac condition or general frailty and will have a limited prognosis. Frequently, they will be cared for by non-cardiac teams who may be less familiar with ICDs. Therefore, to ensure the person receives high-quality end-of-life care, they should have the opportunity to consider and discuss the option to deactivate the shock function of their ICD. If the ICD shock therapy is not discontinued, there is an increased risk that, as a person reaches the last days of life, the ICD may deliver multiple, painful shocks that are distressing. There is also a risk that the device may delay the person's natural death, which the person would not have chosen if they had been given the opportunity to discuss discontinuation. The British Heart Rhythm Society has developed a practical guideline to support all healthcare professionals who are caring for patients who have an ICD. This includes descriptions of different device types, ethical and legal aspects, timing and nature of ICD discussions and practical advice regarding how the devices may be deactivated. It aims to promote awareness and timely discussion between professionals and patients and to encourage best practice.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

Group A beta-haemolytic streptococcal infection in children

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Does proactive care in care homes improve survival? A quality improvement project

BACKGROUND: NHS England's 'Enhanced Health in Care Homes' specification aims to make the healthcare of care home residents more proactive. Primary care networks (PCNs) are contracted to provide this, but approaches vary widely: challenges include frailty identification, multidisciplinary team (MDT) capability/capacity and how the process is structured and delivered. AIM: To determine whether a proactive healthcare model could improve healthcare outcomes for care home residents. DESIGN AND SETTING: Quality improvement project involving 429 residents in 40 care homes in a non-randomised crossover cohort design. The headline outcome was 2-year survival. METHOD: All care home residents had healthcare coordinated by the PCN's Older Peoples' Hub. A daily MDT managed the urgent healthcare needs of residents. Proactive healthcare, comprising information technology-assisted comprehensive geriatric assessment (i-CGA) and advanced care planning (ACP), were completed by residents, with prioritisation based on clinical needs.Time-dependent Cox regression analysis was used with patients divided into two groups:Control group: received routine and urgent (reactive) care only.Intervention group: additional proactive i-CGA and ACP. RESULTS: By 2 years, control group survival was 8.6% (n=108), compared with 48.1% in the intervention group (n=321), p<0.001. This represented a 39.6% absolute risk reduction in mortality, 70.2% relative risk reduction and the number needed to treat of 2.5, with little changes when adjusting for confounding variables. CONCLUSION: A PCN with an MDT-hub offering additional proactive care (with an i-CGA and ACP) in addition to routine and urgent/reactive care may improve the 2-year survival in older people compared with urgent/reactive care alone.Published version, accepted version, submitted versionJournal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

The development and internal pilot trial of a digital physical activity and emotional well-being intervention (Kidney BEAM) for people with chronic kidney disease

This trial assessed the feasibility and acceptability of Kidney BEAM, a physical activity and emotional well-being self-management digital health intervention (DHI) for people with chronic kidney disease (CKD), which offers live and on-demand physical activity sessions, educational blogs and videos, and peer support. In this mixed-methods, multicentre randomised waitlist-controlled internal pilot, adults with established CKD were recruited from five NHS hospitals and randomised 1:1 to Kidney BEAM or waitlist control. Feasibility outcomes were based upon a priori progression criteria. Acceptability was primarily explored via individual semi-structured interviews (n = 15). Of 763 individuals screened, n = 519 (68%, 95% CI 65 to 71%) were eligible. Of those eligible, n = 303 (58%, 95% CI 54-63%) did not respond to an invitation to participate by the end of the pilot period. Of the 216 responders, 50 (23%, 95% CI 18-29%) consented. Of the 42 randomised, n = 22 (10 (45%) male; 49 ± 16 years; 14 (64%) White British) were allocated to Kidney BEAM and n = 20 (12 (55%) male; 56 ± 11 years; 15 (68%) White British) to the waitlist control group. Overall, n = 15 (30%, 95% CI 18-45%) withdrew during the pilot phase. Participants completed a median of 14 (IQR 5-21) sessions. At baseline, 90-100% of outcome data (patient reported outcome measures and a remotely conducted physical function test) were completed and 62-83% completed at 12 weeks follow-up. Interview data revealed that remote trial procedures were acceptable. Participants' reported that Kidney BEAM increased their opportunity and motivation to be physically active, however, lack of time remained an ongoing barrier to engagement with the DHI. An randomised controlled trial of Kidney BEAM is feasible and acceptable, with adaptations to increase recruitment, retention and engagement.Trial registration NCT04872933. Date of first registration 05/05/2021.Published version, accepted version, submitted versionThis article is freely available online. Click on the 'Additional Link' above to access the full-text via the publisher's site

Update Systematic Review, Meta-Analysis and GRADE Assessment of the Evidence on Parastomal Hernia Prevention-A EHS, ESCP and EAES Collaborative Project

Objective: To perform a systematic review and meta-analysis on the effectiveness of prophylactic mesh for the prevention of parastomal hernia in end colostomy, with the ultimate objective to summarize the evidence for an interdisciplinary, European rapid guideline. Methods: We updated a previous systematic review with de novo evidence search of PubMed from inception up to June 2022. Primary outcome was quality of life (QoL). Secondary outcomes were clinical diagnosis of parastomal hernia, surgery for parastomal hernia, and 30 day or in-hospital complications Clavien-Dindo =3. We utilised the revised Cochrane Tool for randomised trials (RoB 2 tool) for risk of bias assessment in the included studies. Minimally important differences were set a priori through voting of the panel members. We appraised the evidence using GRADE and we developed GRADE evidence tables. Results: We included 12 randomized trials. Meta-analysis suggested no difference in QoL between prophylactic mesh and no mesh for primary stoma construction (SMD = 0.03, 95% CI [-0.14 to 0.2], I(2) = 0%, low certainty of evidence). With regard to parastomal hernia, the use of prophylactic synthetic mesh resulted in a significant risk reduction of the incidence of the event, according to data from all available randomized trials, irrespective of the follow-up period (OR = 0.33, 95% CI [0.18-0.62], I(2) = 74%, moderate certainty of evidence). Sensitivity analyses according to follow-up period were in line with the primary analysis. Little to no difference in surgery for parastomal hernia was encountered after pooled analysis of 10 randomised trials (OR = 0.52, 95% CI [0.25-1.09], I(2) = 14%). Finally, no significant difference was found in Clavien-Dindo grade 3 and 4 adverse events after surgery with or without the use of a prophylactic mesh (OR = 0.77, 95% CI [0.45-1.30], I(2) = 0%, low certainty of evidence). Conclusion: Prophylactic synthetic mesh placement at the time of permanent end colostomy construction is likely associated with a reduced risk for parastomal hernia and may confer similar risk of peri-operative major morbidity compared to no mesh placement. There may be no difference in quality of life and surgical repair of parastomal hernia with the use of either approach.Published version, accepted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

Food Allergy Test-Guided Dietary Advice for Children With Atopic Dermatitis: A Consensus Study

BACKGROUND: The use of blood specific IgE or skin prick tests (SPT) to guide dietary exclusions for disease control in children with atopic dermatitis (AD) is controversial. We undertook a consensus exercise on how to interpret SPT results and dietary history for cow's milk, hen's egg, wheat, and soy in children < 2 years old with AD. METHODS: Fourteen clinicians from general practice, pediatrics, pediatric dermatology, pediatric allergy, and pediatric dietetics from UK and Ireland took part in an online modified Delphi study. Over three rounds, participants gave their anonymous opinions and received individualized and group feedback, based on the premise that all children had SPTs. The findings were discussed in an online workshop. RESULTS: Of 18 symptoms, 12 were identified as relevant to immediate and 7 to delayed allergy. Regarding SPTs, there was consensus over which allergens to use for wheat and soy but not cow's milk or hen's egg; for all study foods, wheal size was determined as 0-1 mm negative, ≥ 5 mm sensitized, but between 2 and 4 mm, categorization varied by food. During the final workshop, consensus was reached on dietary advice for nine combinations of SPT results and dietary history. CONCLUSION: We attained consensus on how SPTs and dietary history for four common food allergens should be interpreted in young children under 2 years of age with AD. These pragmatic recommendations may support clinician education, consistency of decision-making, and future research.RDUH staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Considerations of morphometry and phenotypes in modern knee arthroplasty

As advancements in total knee arthroplasty progress at an exciting pace, two areas are of special interest, as they directly impact implant design and surgical decision making. Knee morphometry considers the three-dimensional shape of the articulating surfaces within the knee joint, and knee phenotyping provides the ability to categorize alignment into practical groupings that can be used in both clinical and research settings. This annotation discusses the details of these concepts, and the ways in which they are helping us better understand the individual subtleties of each patient's knee.Not hel