• Carcinoid Heart Disease Revealing the Burden of a Neuroendocrine Tumour: A Case Report.

  Sajeev, Dabeet

  Carcinoid heart disease (CHD) is a rare but serious complication of carcinoid syndrome (CS), typically arising in patients with metastatic neuroendocrine tumours (NETs). Prolonged exposure of the right side of the heart to vasoactive substances such as serotonin leads to progressive valvular fibrosis, predominantly affecting the tricuspid and pulmonary valves, and often culminates in right-sided heart failure. We report the case of a 67-year-old woman with a metastatic small bowel NET who developed CS and later presented with worsening exertional dyspnoea and peripheral oedema. Echocardiography demonstrated severe tricuspid regurgitation and moderate pulmonary regurgitation with preserved left ventricular systolic function. Despite aggressive diuretic therapy, her condition deteriorated, and she developed refractory right-sided heart failure with generalised anasarca. She was not a candidate for valve replacement or further disease-directed therapy due to advanced metastatic disease and frailty and was therefore managed palliatively until she passed away. This case highlights the severe burden of CHD in patients with serotonin-secreting NETs and emphasises the importance of early recognition and regular echocardiographic surveillance to facilitate timely intervention and potentially improve outcomes.
• Continuous Glucose Monitoring in People at High Risk of Diabetes and Dysglycaemia: Transforming Early Risk Detection and Personalised Care

  Liarakos, Alexandros; Wilmot, Emma

  Continuous glucose monitoring (CGM)-based interventions have been predominantly conducted in people with established diabetes. Recently, there has been an increasing interest in using CGM for clinical and research purposes in people without diabetes. In this review, we describe the current evidence regarding the use of CGM in people at high risk of diabetes. To date, there is no strong evidence to support the global implementation of CGM in individuals who are at risk of developing diabetes. However, there are promising results highlighting the benefits of CGM in specific populations such as people living with obesity, prediabetes, gestational diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, other endocrinopathies, and genetic syndromes. Also, CGM has shown promising potential in people with positive islet autoantibodies and pre-symptomatic type 1 diabetes, those treated with medications that induce hyperglycaemia or diabetes, and individuals receiving solid organ transplantation who are at risk of post-transplant diabetes mellitus. However, larger studies are needed to confirm these preliminary results. CGM-derived data are not currently validated for the diagnosis of diabetes. There is no CGM-derived definition of normoglycaemia in people without diabetes. Looking to the future, CGM metrics, in tandem with physical activity, dietary intake, and clinical parameters, and eventually bioinformatics, may inform personalised risk scores for precision prevention of individuals at risk. We conclude that further research is needed to clarify the indications, drawbacks, and feasibility of CGM use in people at high risk of diabetes to identify those groups who could benefit most from this technology.
• Comparative Effects of P2Y12 Inhibitors on Thrombus Biology and Inflammatory Responses in Atherothrombotic Cardiovascular Disease: A Systematic Review of Randomized Controlled Trials.

  Ullah, N; Ali, Mohammed; Khan, Mamoon

  This systematic review investigates the biological impact of various P2Y12 receptor inhibitors on thrombus composition and inflammatory activity in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI). A comprehensive literature search across four major databases identified four randomized controlled trials that met the inclusion criteria for evidence synthesis. These trials examined ticagrelor, prasugrel, cangrelor, and genotype-guided strategies in comparison to clopidogrel, assessing outcomes such as inflammatory cell infiltration, platelet reactivity, and myocardial reperfusion parameters. Overall, ticagrelor and prasugrel were associated with more favorable modulation of thromboinflammatory and vascular healing markers compared with clopidogrel; these effects were most evident in studies evaluating neutrophil infiltration, myeloperoxidase activity, and early post-PCI ischemic events. However, variations in study design, endpoints, and follow-up duration limited direct comparisons and precluded definitive conclusions. In addition, one mechanistic study protocol describing the assessment of extracellular vesicle-based biomarkers was identified but excluded from the evidence synthesis due to the absence of outcome data. Collectively, the available evidence provides preliminary mechanistic support for the hypothesis that certain P2Y12 inhibitors may exert anti-inflammatory and thrombus-modifying effects beyond their platelet-inhibiting effects. Larger, standardized, and mechanistically focused trials are warranted to validate these findings and guide precision-based antiplatelet therapy in cardiovascular disease.
• From acute to chronic: the long-term consequences of AKI in South and Southeast Asia.

  Selby, Nicholas
• Revision of total elbow arthroplasty due to humeral loosening with large bone defect using humeral allograft-prosthesis composite: A case report.

  Cresswell, Timothy

  INTRODUCTION AND IMPORTANCE: Revision of total elbow arthroplasty is a challenging procedure, especially when associated with humeral bone deficiency. The purpose of this case report is to highlight the successful management of humeral-sided loosening due to bone defects, using an allograft-prosthesis composite with a humeral bone allograft. PRESENTATION OF CASE: A 70-year-old female patient under medication for rheumatoid arthritis underwent revision of left total elbow arthroplasty due to major bone defect and loosening on the humeral side. The allograft-prosthesis composite method was used to address the bone defect and loosening of the humeral side by using humeral allograft as well as plating the host humeral bone. CLINICAL DISCUSSION: There were no post-operative complications. The radiographic assessment at her latest follow-up was unremarkable, along with a significant improvement on the functional scores and range of motion. CONCLUSION: The use of a humeral allograft is a valuable option for the management of loosened total elbow arthroplasty with significant bone loss. However, more studies need to be conducted to determine the long-term outcomes of revision surgery of total elbow arthroplasty with humeral bone loss.
• Global prevalence of metabolic syndrome in patients with Rheumatoid arthritis: a systematic review and meta-analysis.

  Abdul, RHM

  BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that increases the risk of systemic complications, particularly metabolic syndrome (MetS). MetS, defined by central obesity, hypertension, hyperglycemia, and dyslipidemia, not only raises cardiovascular risk but also worsens the prognosis of RA. This meta-analysis aimed to estimate the global prevalence of MetS in RA patients and identify clinical factors contributing to its occurrence. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science. Studies included in the analysis diagnosed RA and defined MetS using standardized guidelines. Pooled estimates were calculated using a random-effects model. Heterogeneity was assessed using the I² statistic. All statistical analyses were conducted using Stata. The study is registered with PROSPERO (CRD420251007337). RESULTS: The overall pooled prevalence of MetS among RA patients was 30.3% (95% CI: 28.5-32.2). Country-specific analyses showed the highest prevalence in Iraq (57.3%; 95% CI: 49.7-66.4), Croatia (49.6%; 95% CI: 35.8-63.3), and Singapore (47.1%; 95% CI: 42.7-51.6), and the lowest in Congo (12.0%; 95% CI: 5.5-20.5), Algeria (14.0%; 95% CI: 10.0-18.7), and South Korea (17.2%; 95% CI: 7.3-30.1). When stratified by continent, the estimates varied noticeably. In Africa, the proportion was 25.7% (95% CI: 21.6-30.0%); in Asia, the estimate rose to 30.8% (95% CI: 27.1-34.6%); Europe recorded a similar figure at 29.8% (95% CI: 26.9-32.7%); North America had an estimate of 31.1% (95% CI: 25.5-36.9%); and South America demonstrated the highest proportion at 38.8% (95% CI: 34.4-43.3%). Meta-regression analyses identified significant associations between MetS prevalence and key clinical variables, including waist circumference (WC) (β = 0.01; P = 0.01), body mass index (BMI) (β = 0.04; P < 0.01), triglycerides (TG) (β < 0.01; P = 0.04), and fasting blood glucose (FBG) (β < 0.01; P < 0.01), with high-density lipoprotein (HDL) levels showing an inverse association (β = -0.01; P < 0.01). Among various diagnostic criteria, the highest prevalence estimates were obtained with the National Cholesterol Education Program and International Diabetes Federation (NCEP/IDF) criteria (39.2%; 95% CI: 30.6-48.1), followed by the Joint Consensus (JC) criteria (37.2%; 95% CI: 28.0-46.9) and the 2004 revision of the National Cholesterol Education Program ATP III (NCEP 2004) criteria (35.4%; 95% CI: 29.0-42.0). CONCLUSION: The substantial prevalence of MetS among RA patients underscores the need for a proactive, integrated approach to cardiovascular risk management. Clinicians should consider routine screening for MetS components-such as central obesity, hypertension, dysglycemia, and dyslipidemia-particularly given the significant associations with WC, BMI, TG, and FBG levels. CLINICAL TRIAL NUMBER: Not applicable.
• Continuous glucose monitoring and automated insulin delivery systems in the management of diabetes among individuals with chronic kidney disease on dialysis.

  Liarakos, Alexandros; Randhay, Ashveer; Wilmot, Emma

  PURPOSE OF REVIEW: To describe the current evidence and emerging role of continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems in the management of diabetes among individuals with advanced chronic kidney disease (CKD) undergoing dialysis. RECENT FINDINGS: Recent studies have shown that CGM provides accurate and clinically useful glucose data in people with advanced CKD requiring dialysis. CGM enables the detection of glycaemic variability and hypoglycaemia patterns that are often missed by traditional monitoring methods, such as capillary blood glucose testing and haemoglobin A1c. While observational studies show benefits, randomised controlled trial data are limited. Early trials and case series suggest that AID, especially fully closed-loop systems, may improve glycaemia in dialysis-dependent individuals with diabetes, though evidence is currently sparse and primarily focused on type 2 diabetes. Several ongoing and planned studies aim to address these knowledge gaps. SUMMARY: CGM represents a valuable tool for improving glucose management and safety in people with diabetes and advanced CKD, but barriers to widespread use, such as cost, access, and healthcare provider familiarity, remain significant. AID technologies show promise but require further evaluation in this population. Future research should prioritise long-term outcomes, cost-effectiveness, and patient-reported outcomes to support the integration of these technologies into routine care for this high-risk group.
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  Empagliflozin Treatment for Non-alcoholic Fatty Liver Disease in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

  Rahman, Mohammed Abdul

  Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has emerged as a promising therapeutic option for patients with concurrent type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). This systematic review and meta-analysis evaluated the efficacy of empagliflozin on liver enzymes and metabolic parameters in this dual-pathology population. A comprehensive search was conducted across PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases from inception to July 2025. Randomized controlled trials (RCTs) comparing empagliflozin with placebo in adults with T2DM and NAFLD were included. Primary outcomes included changes in liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)), while secondary outcomes comprised systolic blood pressure (SBP) and glycated hemoglobin (HbA1c) levels. Four studies met the inclusion criteria, encompassing 393 participants (206 empagliflozin, 187 control) with follow-up periods ranging from 20 to 24 weeks. Meta-analysis demonstrated significant reductions in ALT (mean difference (MD): -11.61; 95% confidence interval (CI): -19.18 to -4.04), AST (MD: -10.31; 95% CI: -15.41 to -5.21), and GGT levels (MD: -15.19; 95% CI: -18.13 to -12.25) with empagliflozin treatment compared to placebo. However, no statistically significant differences were observed for SBP (MD: -0.87; 95% CI: -7.93 to 6.20) or HbA1c (MD: -0.44; 95% CI: -1.10 to 0.22). Considerable heterogeneity was noted across studies for most outcomes. These findings suggest that empagliflozin offers hepatoprotective benefits in patients with concurrent T2DM and NAFLD, primarily through significant improvements in liver enzyme profiles. However, larger long-term studies with histological endpoints are needed to establish definitive clinical recommendations for this therapeutic approach.
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  A multi-center, prospective, single-arm, open label, 13-month intervention study of a plant-based, high energy and protein enteral tube feed in home enterally tube fed patients.

  Owen, Stephanie

  INTRODUCTION: There is an emerging need for plant-based options for home enteral tube feeding (HETF) patients, however their long-term efficacy and safety needs to be established. METHODS: Forty-one HETF patients (age: 51 years (SD 23); range 19-84 years; 54% male) participated in a multi-center, prospective, single-arm, open label, 13-month intervention study of a plant-based, high energy, high protein (2 kcaL/mL and 10 g protein/100 mL) enteral tube feed with or without added fiber (1.5 g/100 mL). Seventeen patients continued on the plant-based feed beyond day 28 (28 D) with a 6- and 13-month follow-up (6 M and 13 M). Outcomes included gastrointestinal tolerance (GI), anthropometrics, muscle strength and function (handgrip strength, 30-s chair stand test (30SCST)), dietary intake, total daily feed volume and time for feeding, and safety. RESULTS: Compared to patient's baseline feeding regimen, patients using the plant-based feed reported: greater absence of GI symptoms at all time points (+7-12%, p ≤ 0.04); a reduced incidence and intensity of GI symptoms: bloating, burping at 28 D (p < 0.05) and constipation, flatulence at 13 M (p < 0.05); improved physical function between 6 M and 13 M (+2 30SCST repetitions, p = 0.02), with maintenance of body weight, calf circumference and handgrip strength; total protein intake increased at all time points (+0.2-0.3 g/kg/day, p < 0.05); and total daily feed volume (-225 to -264 mL/day, p < 0.05) and estimated time for pump feeding (-2 h/day, p < 0.05) reduced at all time points. DISCUSSION: This longitudinal study highlights that a plant-based (vegan-suitable) high energy, high protein enteral tube feed has good tolerance in HETF patients, positive long-term effects on protein intake and potential benefits on physical function.
• The REDUCE Intervention: The Development of a Person-Centred Cognitive Behavioural Intervention to Improve Ulcer Outcomes in People at Risk of Diabetic Foot Ulceration.

  Game, Frances

  INTRODUCTION: Diabetic foot ulcers (DFUs) affect approximately one-quarter of people living with diabetes. They are chronic, recur frequently and are associated with significant psychological distress and behavioural challenges. The REDUCE intervention is a person-centred, cognitive behavioural intervention designed to reduce the risk of DFU recurrence and support ulcer healing. Here, we describe the iterative development and optimisation of REDUCE, from its inception as a group-based intervention to an individually tailored intervention delivered via video call or telephone. We outline key stages of the intervention development, including the integration and modification of a digital maintenance intervention (DMI) designed to support long-term behaviour change and a mixed-methods external pilot trial which informed a full-scale clinical and cost-effectiveness trial. METHODS: After initial development, the DMI was the subject of nine 'think-aloud' interviews with patient and public contributors. We conducted an external pilot randomised controlled trial, involving 20 patients with recently healed DFUs randomised in a 2:1 ratio (REDUCE + Usual Care vs. Usual Care only). Data collection included patient-reported outcome measures (baseline and 6 weeks and 3 months post-randomisation) and qualitative interviews with participants and facilitators. RESULTS: Think-aloud interviews informed key refinements to the DMI to enhance usability and engagement. The pilot trial demonstrated high acceptability of the intervention format and delivery. Patient-reported outcomes suggested positive trends in psychological well-being, footcare behaviours and mood among intervention participants. Qualitative findings highlighted the value of individualised delivery, the importance of facilitator support and varied engagement with the DMI. These insights informed further refinements to REDUCE ahead of a full-scale effectiveness trial. CONCLUSION: We provide a comprehensive account of the evolution of the REDUCE intervention and share broader learnings regarding the development of complex behavioural health interventions. The example of REDUCE highlights the value of iterative, multidisciplinary methods and patient involvement in intervention design and offers practical insights for designing digital and remote health interventions. PATIENT OR PUBLIC CONTRIBUTION: Patient and public contributors were involved throughout the research described in this manuscript. Key areas of involvement included co-creation of all patient-facing materials, intervention development and informing trial methods.
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  Mood Disturbances in a Patient on Statin Therapy: A Case Report.

  Sajeev, Dabeet

  Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are widely used to treat hyperlipidaemia and significantly reduce the risk of cardiovascular events. While generally well tolerated, emerging evidence suggests that statins may, in rare cases, be associated with neuropsychiatric adverse effects, including mood disturbances and behavioural changes. We report the case of a 54-year-old woman with hypertension, but no personal or family history of psychiatric illness, who developed mood and behavioural changes shortly after initiating atorvastatin 10 mg following the detection of dyslipidaemia on routine blood testing. Her regular medications included bisoprolol and amlodipine, which she had been taking for eight years without any prior neuropsychiatric side effects. Symptoms resolved rapidly upon discontinuation and recurred upon rechallenge, prompting cessation and referral for psychological counselling. The Naranjo Adverse Drug Reaction (ADR) Probability Scale yielded a score of 8, indicating a probable relationship between the statin and the mood disturbances. Although uncommon, statin-induced neuropsychiatric symptoms have been documented in genetic studies and pharmacovigilance databases. Proposed mechanisms include reduced central nervous system cholesterol affecting serotonergic neurotransmission and statin-related modulation of cytokine signalling. This case highlights the importance of clinician awareness of potential mood-related side effects of statins, even in patients without prior psychiatric history or those receiving low doses. Early recognition and timely management can minimise patient distress and support safer long-term adherence to lipid-lowering therapy.
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  Management of Early-Onset Type 2 Diabetes in Adults: Current Evidence and Future Directions.

  Wilmot, Emma

  The global prevalence of early-onset type 2 diabetes (EOT2D) is rising rapidly. Adults with EOT2D represent a high-risk population characterised by increased rates of microvascular and macrovascular complications, adverse psychological wellbeing and psychiatric comorbidities such as depression, and premature mortality compared to those with later-onset type 2 diabetes mellitus. This emerging population faces unique challenges, including high levels of diabetes-related stigma, clinical inertia, and competing life demands, such as starting a family. This review synthesises current evidence on the clinical management of EOT2D. Key therapeutic targets include weight reduction, preservation of β-cell function, cardiometabolic risk management, and psychological support. Overall, there are few randomized controlled trials (RCTs) undertaken specifically in adults with EOT2D. However, we summarise early data from the few RCTs that do report outcomes specific in young adults, with bariatric surgery, tirzepatide and intensive lifestyle interventions emerging as particularly effective treatments. There is a strong rationale that technology-based inventions and structured education programs may prove to be effective treatments but data from RCTs is lacking. We provide broad recommendations for future research and clinical practice based on the current evidence. In conclusion, substantial further research is required to inform tailored, evidence-based guidelines and improve long-term outcomes in this underserved population.
• Metformin for Central Centrifugal Cicatricial Alopecia: Emerging Antifibrotic Evidence and Mechanistic Insights.

  Aboluwarin, Oluwamayowa
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  Efficacy and Safety of Vitamin E in Adults With Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

  Rahman, Mohammed Abdul

  This systematic review and meta-analysis evaluated the efficacy and safety of vitamin E supplementation in adults with metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH). A comprehensive search of PubMed, Cochrane Library, Embase, and Scopus databases was conducted from inception to May 25, 2025, identifying randomized controlled trials comparing vitamin E versus placebo in MASH patients. After screening 752 records, three high-quality randomized controlled trials were included in the final analysis. The pooled analysis demonstrated that vitamin E significantly reduced serum alanine aminotransferase levels compared to placebo (mean difference (MD): -12.27, 95% confidence interval (CI): -16.66 to -7.89) and aspartate aminotransferase levels (MD: -7.08; 95% CI: -14.93 to 0.76). Vitamin E was associated with significantly higher odds of fibrosis improvement (odds ratio (OR): 1.96, 95% CI: 1.25-3.09) with no heterogeneity observed across studies. However, MASH resolution showed no statistically significant difference between groups (OR: 1.71, 95% CI: 0.69-4.27) with substantial heterogeneity, though sensitivity analysis excluding one study revealed a significant benefit. The studies varied in vitamin E dosing from 300 to 800 mg daily, with two conducted in the United States and one in China. These findings suggest that vitamin E supplementation provides biochemical and histological benefits in MASH patients, particularly in reducing liver enzyme levels and improving fibrosis. However, the limited number of trials and varying outcome definitions highlight the need for larger, standardized multinational studies to establish optimal dosing recommendations and long-term safety profiles.
• Evolution of multidisciplinary obesity treatments: past, present, and future role of nutrition.

  Atherton, P

  Obesity is a complex chronic disease requiring lifelong comprehensive treatment. In addition to lifestyle counseling that improves nutrition and physical activity, a promising new generation of obesity medications has been added to bariatric procedures as therapeutic options to achieve weight reduction and improve health outcomes. With the promise of effective and safe treatments comes the need to emphasize maximal reduction of body fat and minimal loss of vital body components, including skeletal muscle and bone. Nutrition is a critical aspect of obesity care and is leveraged to support preservation of lean tissues, such as skeletal muscle, through adequate, daily, high-quality protein intake and intake of key micronutrients. More targeted nutrition approaches that promote muscle protein synthesis include amino acid supplementation with leucine and its metabolite β-hydroxy β-methylbutyrate. Another potential target for support is the gut microbiome, as its adequate function is increasingly seen as playing a role in human health and metabolism. Obesity is a heterogenous disease, and there is considerable interest in specific metabolic phenotypes that might be used to tailor nutrition strategies. As research advances on these and other fronts, there is the potential to identify precision nutrition strategies for individualized, more effective approaches to lifelong obesity management.
• Understanding recovery after acute kidney injury.

  Torr, Leah

  Acute kidney injury (AKI) is not an isolated event, however, is often the start of a long-term risk trajectory for patients. While in many cases kidney function improves, dysfunction is common and carries a heightened risk of chronic kidney disease (CKD), as well as cardiovascular morbidity and mortality. Central to improving outcomes is a clear, practical understanding of what constitutes true ‘recovery’ from AKI. Yet, current definitions are inconsistent, ranging from simplistic biochemical thresholds to more nuanced, qualitative judgments. To better understand how AKI recovery is defined in practice within the UK, the UK Kidney Association (UKKA) Special Interest Group and the Association of Nephrology Nurses UK (ANN UK) AKI Community of Practice surveyed nurses working in specialist AKI roles. The survey was sent to all AKI nurses from the ANN UK AKI CoP group via email. This group were chosen as a convenience sample of specialist practitioners who were caring for people with AKI and aimed to gain an insight into how nurses working in AKI care viewed and used AKI recovery. The survey received responses from 18 AKI nurses across 16 NHS Trusts within the UK. The survey explored how these clinicians define baseline renal function, assess recovery and approach follow-up, while also reviewing awareness and use of terms such as acute kidney disease.
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  Toward Standardized Performance Metrics in the Cardiovascular ICU: A Systematic Review of Quality Indicators.

  Ibrahim, Ensaf

  The cardiovascular intensive care unit (CVICU) requires robust quality indicators (QIs) to standardize performance measurement and improve patient outcomes. However, heterogeneity in QI definitions, measurement tools, and implementation practices persists. This systematic review synthesizes evidence on CVICU QIs, evaluates their methodological rigor, and proposes a framework for standardization. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we searched PubMed, Embase, Scopus, Web of Science, and CINAHL for relevant studies. Eight studies met the inclusion criteria, encompassing retrospective cohorts, predictive models, and mixed-methods designs. Quality assessment employed the Newcastle-Ottawa Scale (NOS) for cohort studies and the Mixed Methods Appraisal Tool (MMAT) for non-randomized studies. Narrative synthesis categorized QIs by Donabedian domains (structure, process, outcome). Included studies (n=8) predominantly focused on outcome QIs (5/8 studies), particularly mortality prediction using machine learning. Risk of bias was moderate to high, with most studies lacking prospective validation or objective measurements. Structural QIs were especially underrepresented, and although Delphi methods were employed, they lacked external validation and reproducibility, limiting generalizability. Process QIs relied on subjective surveys, while structural QIs lacked robust measurement frameworks. Alignment with Donabedian and Institute of Medicine (IOM) frameworks was reported in 6/8 studies, yet consistency in application was limited. CVICU QIs prioritize outcome measurement through artificial intelligence (AI)-driven tools but lack standardization in the development, validation, and operationalization of process and structural indicators. Future work should (1) validate predictive models in multicenter, prospective settings, (2) develop objective and reproducible process metrics, and (3) expand structural QIs for global applicability, accounting for resource constraints, variability in infrastructure, and cultural differences in care delivery. Given the limited number of studies, findings should be interpreted cautiously and considered hypothesis-generating rather than definitive. This review informs efforts to harmonize CVICU performance measurement.
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  Mannitol for cerebral oedema after acute intracerebral haemorrhage (MACE-ICH): protocol for a prospective, randomised, open-label, blinded-endpoint phase IIb trial.

  England, Timothy J.

  BACKGROUND: Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an osmotic diuretic, is used to treat cerebral oedema after traumatic brain injury, but its safety and efficacy in ICH is unclear. We aim to assess the feasibility of a phase II randomised, controlled trial of mannitol in patients with ICH with, or at risk of, cerebral oedema to inform a definitive trial. METHODS: The mannitol for cerebral oedema after acute intracerebral haemorrhage trial (MACE-ICH) aims to include 45 ICH participants from 10 UK sites with estimated largest diameter of haematoma volume >2 cm, presenting within 72 hours of onset with, or at risk of, cerebral oedema (limited Glasgow Coma Scale (GCS)<9, including motor and visual components only, and National Institutes of Health Stroke Scale>8) with or without mass effect. Participants will be randomised (1:1:1) to 1 g/kg 10% single-dose intravenous mannitol, 1 g/kg 10% mannitol followed by a second dose at 24 hours, or standard care alone. Outcome assessors will be masked to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, participants receiving allocated treatment, recruitment rate, treatment adherence and follow-up. Secondary outcomes include serum electrolytes and osmolality at days 1-2; change in ICH and oedema volume at day 5; number of participants who developed urinary tract infection, GCS and National Institutes of Health Stroke Scale at day 5±2; length of hospital stay, discharge destination and death up to day 28; death and death or dependency by day 180 and disability (Barthel Index), quality of life (EuroQol, 5-D) and cognition (telephone mini-mental state examination) at day 180. ETHICS AND DISSEMINATION: MACE-ICH received ethics approval from the East Midlands-Leicester Central research ethics committee (22/EM/0242). The trial is funded by a National Institute for Health and Care Research RfPB grant (203080). The results will be published in an academic journal and disseminated through academic conferences and patient support groups. Reporting will be in line with Consolidated Standards of Reporting Trials recommendations. TRIAL REGISTRATION NUMBERS: ISRCTN15383301; EUDRACT 2022-000283-22.
• The Implications of Type 1 Diabetes Mellitus Associated with Coeliac Disease.

  Holmes, Geoffrey

  T1D and CD commonly occur together. This association has received increasing attention from researchers and is considered in detail in this review. Since CD is over-represented in T1D, it may cause ill health with attendant complications, but because there is an effective dietary treatment, screening has been recommended in children and adults. However, there are many unknowns regarding this association, and understanding the why, when, and how with regard to screening and managing those with dual diagnoses requires thorough consideration when introducing the concept of screening to patients. It is important that patients and, where appropriate, carers are put at the heart of the decision-making process with careful discussion of the issues involved before undertaking screening that might uncover a second life-changing diagnosis, for which, without preparatory preparation and support, individuals may be ill-prepared, causing mental health issues. For some patients, an initial policy of monitoring rather than moving to immediate small bowel biopsy and exposure to a gluten-free diet (GFD) will be appropriate. The correct management of patients will ultimately improve their quality of life medically and socially.
• Personalized Care in CKD: Moving Beyond Traditional Biomarkers.

  Taal, Maarten

  BACKGROUND: Traditional biomarkers, such as estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (uACR), have long been central to chronic kidney disease (CKD) diagnosis and management, leading to a standardized CKD classification system. However, these biomarkers are non-specific and fail to capture the heterogeneity within CKD and the nuances of an individual's disease mechanism, limiting personalized treatment approaches. There is an increasing need for novel biomarkers that reflect the diverse pathophysiological processes underlying CKD progression, enabling more precise risk prediction and treatment strategies. SUMMARY: This review examines the limitations of current CKD biomarkers and classification systems, highlighting the need for a precision medicine approach. While traditional markers like eGFR and uACR are foundational, they inadequately capture CKD's complexity. Emerging biomarkers offer insights into specific disease processes, such as inflammation, oxidative stress, fibrosis, and tubular injury, which are crucial for personalized care. The article discusses the potential benefits of integrating these novel biomarkers into clinical practice, including more accurate risk prediction, tailored treatments, and personalized clinical trial designs, as well as the barriers to their implementation. Furthermore, advancements in multi-omics and high-throughput techniques offer opportunities to identify novel causative proteins with druggable targets, pushing CKD care towards greater precision. KEY MESSAGES: Current CKD classification systems, based on non-specific biomarkers, fail to capture CKD's heterogeneity. Incorporating biomarkers reflecting diverse pathophysiological mechanisms can enhance risk prediction, customized treatments, and personalized clinical trials. High-throughput multi-omic techniques present a promising path towards precision medicine in nephrology.

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