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BMJ (Clinical research ed.)
Advances in the drug treatment of Alzheimer's disease: pathophysiology and mechanisms of action
Nowell J, Crook H, de Leon MJ et al. · 2026 Apr 20
Study Type: Narrative review
Key Question: What are the current and emerging drug treatments for Alzheimer's disease and their mechanisms of action?
Key Findings: - Anti-amyloid beta therapies have demonstrated clinical efficacy and gained licensing in several countries, though amyloid-related imaging abnormalities remain a significant safety concern
- Cognitive decline may continue after amyloid clearance, suggesting amyloid-independent pathological mechanisms drive disease progression
- Future effective treatment will likely require combination therapies targeting multiple pathways including tau aggregation, neuroinflammation, synaptic loss, and metabolic dysfunction
Clinical Relevance: UK acute medicine clinicians may increasingly encounter patients on anti-amyloid therapies requiring monitoring for imaging abnormalities, and should understand the multifactorial nature of Alzheimer's disease as combination treatments emerge.
Limitations: As a narrative review, this provides expert opinion rather than systematic evidence synthesis of therapeutic efficacy.
Anesthesia and analgesia
Pulse Oximeter Performance and Skin Pigment: Comparison of 34 Oximeters Using Current and Emerging Regulatory Frameworks
Hughes C, Chen D, Law T et al. · 2026 Apr 20
Study Type: Laboratory-based controlled desaturation study
Key Question: How do 34 pulse oximeters perform across different skin pigmentations under current and proposed regulatory frameworks?
Key Findings: - Using current standards, 82% (28/34) passed 2017 ISO criteria and 65% (22/34) passed 2013 FDA guidance
- Under proposed stricter regulations, only 62% (21/34) would pass anticipated ISO standards and just 3% (1/34) would pass anticipated FDA criteria
- Only 11/34 oximeters showed the expected pattern of more positive bias in darker-skinned participants (median difference 1.42% SpO2)
Clinical Relevance: UK anaesthetists should be aware that most pulse oximeters in current use may not meet emerging regulatory standards for skin pigmentation bias, potentially affecting patient safety monitoring across diverse populations.
Limitations: Laboratory conditions with controlled desaturation may not reflect real-world clinical performance and patient acuity.
Circulation
JNK2 Is a Stress Integrator Driving Atrial Fibrillation Pathogenesis in Aging via Gut-Heart Crosstalk
Yan J, Carrillo E, Kohli A et al. · 2026 Apr 20
Study Type: Experimental study using multiple mouse models
Key Question: Does cardiac JNK2 kinase integrate stress signals from gut barrier dysfunction to drive atrial fibrillation pathogenesis in aging?
Key Findings: - Leaky gut significantly activated atrial JNK2, increasing AF inducibility in aged, dextran sulfate sodium-treated, and occludin knockdown mice
- Restoration of gut barrier function reduced AF susceptibility, while JNK2 inhibition or TNF-α blockade abolished leaky gut-associated AF risk
- Gut-derived inflammatory cytokines (TNF-α, IL-17A) and lipopolysaccharide activated cardiac JNK2, promoting arrhythmogenic calcium handling abnormalities including diastolic SR calcium leak and delayed afterdepolarisations
Clinical Relevance: This identifies a novel gut-heart axis mechanism for age-related AF, potentially explaining why anti-inflammatory therapies have shown inconsistent results and suggesting JNK2 as a therapeutic target for AF prevention in elderly patients.
Limitations: Animal model findings may not directly translate to human AF pathophysiology and clinical outcomes.
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
A Novel Pulsatile Excised Porcine Lung Model for Realistic Anatomic Lung Resection Training: A Pilot Study
Kawamura T, Yanagihara T, Sugai K et al. · 2026 Apr 01
Study Type: Pilot study
Key Question: Can a novel pulsatile porcine lung model with microbead-filled pulmonary arteries provide realistic anatomic lung resection training without pulmonary oedema?
Key Findings: - Microbead infusion reduced pulmonary oedema significantly (mean weight gain 16.4g vs 457.0g in controls, P=0.027)
- Eight trainees showed significant improvement in lobectomy time from first to second attempt (39 min 17s to 32 min 52s, P=0.012)
- 75% rated vascular manipulation as realistic; 100% found training beneficial
Clinical Relevance: This training model could enhance surgical education for UK cardiothoracic trainees by providing realistic pulsatile vessel simulation for lobectomy and vascular repair skills development.
Limitations: Very small pilot study with only 8 trainees limits generalisability of findings.
JAMA dermatology
Stapokibart for the Treatment of Refractory Palmoplantar Pustulosis
Liu X, Wu Y, Liu Z et al. · 2026 Apr 22
Study Type: Cannot be determined - abstract text not provided.
Key Question: Cannot be determined without the abstract content.
Key Findings: - Abstract text is missing, preventing extraction of study findings
- Only title indicates this relates to stapokibart treatment for refractory palmoplantar pustulosis
Clinical Relevance: Cannot assess clinical relevance without access to the study methodology, results, and conclusions from the abstract.
Limitations: Cannot evaluate study limitations as the abstract content is not available for review.
Note: To provide a meaningful clinical summary, the full abstract text is required. The title suggests this study examines stapokibart (likely a novel therapeutic agent) for treating refractory palmoplantar pustulosis, a challenging inflammatory skin condition affecting palms and soles that often responds poorly to conventional therapies.
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine
Multi-Factorial and Multi-Component Fall Prevention Interventions Initiated From the Emergency Department: A Systemic Review and Meta-Analysis
Southerland LT, Mowbray FI, Tarnovsky IA et al. · 2026 Apr
Study Type: Systematic review and meta-analysis
Key Question: Do multi-factorial and multi-component fall prevention interventions initiated from the emergency department reduce falls in older adults aged ≥60 years?
Key Findings: - No reduction in fall risk at 3, 6, or 12 months (risk differences ranging from -0.02 to 0.07, with confidence intervals crossing null)
- No change in ED revisits at 1, 3, or 12 months, nor in mortality or hospitalisation rates
- Functional status improved in 4 of 5 studies that measured this outcome
Clinical Relevance: Despite national guideline endorsement, ED-initiated comprehensive fall prevention programmes do not appear to reduce falls or healthcare utilisation in older adults, challenging current UK emergency medicine practice recommendations.
Limitations: High heterogeneity in intervention types, settings, and outcome timing limits the ability to draw definitive conclusions about specific intervention components.
Diabetes care
The Importance of C-Peptide for Developing T1D Disease-Modifying Therapies
Fleming GA, Mathieu C, Skyler JS · 2026 Apr 20
Study Type: Commentary
Key Question: Should C-peptide be reinstated as a regulatory endpoint for full approval of type 1 diabetes disease-modifying therapies?
Key Findings: - Preserved β-cell function (measured by C-peptide) correlates with better glycaemic control, fewer microvascular complications, and reduced hypoglycaemia risk in T1D
- The FDA accepted C-peptide as a primary efficacy endpoint from 2008-2023 but subsequently removed it from the Surrogate Endpoint Table for unclear reasons
- Current regulatory pathways requiring clinical endpoints create lengthy approval processes that may delay access to potentially beneficial therapies
Clinical Relevance: This advocacy piece addresses a key barrier to developing new T1D treatments that could benefit patients managed in NHS diabetes services by potentially accelerating regulatory approval timelines.
Limitations: This is an opinion piece rather than original research, providing advocacy arguments without new empirical evidence.
Gastroenterology
AGA Clinical Practice Update on Risk Stratification and Emerging Surveillance Strategies for Hepatocellular Carcinoma: Expert Review
Rich NE, Villanueva A, Marrero JA et al. · 2026 Apr 15
Study Type: Expert review and clinical practice update
Key Question: What are the best practices for hepatocellular carcinoma risk stratification and surveillance strategies in at-risk populations?
Key Findings: - Current surveillance (6-monthly ultrasound plus α-fetoprotein) remains standard but has suboptimal sensitivity, with <25% of cirrhotic patients receiving appropriate surveillance
- Novel biomarkers like GALAD are commercially available but lack sufficient validation for routine use and should not replace guideline-recommended tests
- For chronic hepatitis B without cirrhosis, PAGE-B and REAL-B scores can effectively stratify HCC risk, but surveillance is not recommended for non-cirrhotic patients with other liver disease aetiologies
Clinical Relevance: Provides updated guidance for UK gastroenterologists on HCC surveillance implementation, particularly relevant given rising HCC burden in non-viral liver disease (MASLD, alcohol-related) within NHS patient populations.
Limitations: Expert opinion-based without systematic literature review, so recommendations lack formal evidence quality ratings.
BMJ (Clinical research ed.)
Advances in the drug treatment of Alzheimer's disease: pathophysiology and mechanisms of action
Nowell J, Crook H, de Leon MJ et al. · 2026 Apr 20
Study Type: Narrative review
Key Question: What are the current advances and future directions in drug treatments for Alzheimer's disease beyond amyloid-targeting therapies?
Key Findings: - Anti-amyloid beta therapies have demonstrated clinical efficacy and gained licensing in several countries, though amyloid-related imaging abnormalities remain a key safety concern
- Cognitive decline continues after amyloid clearance, suggesting amyloid-independent pathological mechanisms drive disease progression
- Future treatment approaches are shifting toward combination therapies targeting multiple pathways including tau aggregation, neuroinflammation, synaptic loss, and metabolic dysfunction
Clinical Relevance: UK GPs should understand that Alzheimer's treatment is evolving beyond single-target approaches, with implications for patient counselling about emerging therapies and potential referral pathways as multimodal treatments become available through NHS specialist services.
Limitations: As a narrative review, this does not provide systematic evaluation of treatment efficacy or safety data.
Annals of surgery
Metabolic and Bariatric Surgery vs Glucagon-like peptide-1 Receptor Agonist Therapy: A Head-to-Head Comparison in Improvement of Cardiometabolic Risk Profiles
Ghusn W, Vierkant RA, Jawhar N et al. · 2026 Apr 20
Study Type: Retrospective cohort study
Key Question: How do metabolic and bariatric surgery and GLP-1 receptor agonists compare for reducing cardiovascular risk in adults with obesity?
Key Findings: - Both treatments reduced 10-year ASCVD risk similarly (-0.8% vs -1.1%, p=0.36), but bariatric surgery achieved significantly greater lifetime ASCVD risk reduction (-8.6% vs -1.7%, p<0.001)
- Bariatric surgery produced superior weight loss (-27.8% vs -11.1%, p<0.001) and more favourable lipid profile changes
- After adjustment, bariatric surgery remained independently associated with greater lifetime ASCVD risk reduction (β -6.92, 95% CI -9.22 to -4.62)
Clinical Relevance: This evidence supports bariatric surgery as the more effective long-term cardiovascular risk reduction strategy for obese patients, informing MDT discussions and referral decisions within NHS obesity services.
Limitations: Retrospective design with potential selection bias, as GLP-1RA patients were older with higher baseline cardiovascular risk.
Age and ageing
Heat-related deaths in social care in England: can the Care Quality Commission ratings system be used to identify care homes that would benefit most from heat adaptation measures?
Hajat S, Hussein S, Li K et al. · 2026 Apr 04
Study Type: Time-series regression analysis using national data
Key Question: What is the risk of heat-related mortality in English care homes, and can CQC ratings identify facilities needing priority heat adaptation measures?
Key Findings: - During July 2022 heatwave, nursing home deaths increased by 34.1% (95% CI 21.1-48.2%) and residential care deaths by 13.0% (0.1-27.0%)
- On 25°C days versus 16°C days (2022-24), death risk was 2.09 times higher in nursing homes (95% CI 1.68-2.60) and 1.56 times higher in residential care (1.24-1.96)
- Poorer CQC ratings showed gradient of increasing heat mortality risk, with highest risks in West Midlands and London
Clinical Relevance: This demonstrates substantial heat vulnerability among care home residents across England, providing evidence for urgent implementation of heat adaptation strategies in social care settings serving our frailest older adults.
Limitations: Study period limited to recent years may not capture longer-term temperature-mortality relationships or account for evolving care practices.
Blood
Molecular mechanism of cleavage at R271 during prothrombin activation revealed by cryo-EM
Stojanovski B, Mohammed BM, Basore K et al. · 2026 Apr 20
Study Type: Structural biology study using cryo-electron microscopy
Key Question: How does the prothrombinase complex achieve the second proteolytic cleavage at R271 to convert meizothrombin to active thrombin?
Key Findings: - Cryo-EM structure at 3.8 Å resolution revealed the molecular mechanism of R271 cleavage in meizothrombin activation
- Cleavage site switching from R320 to R271 requires significant reorientation (>20 Å movement) of the protease domain rather than conformational changes
- Molecular contacts primarily involve protease domains of meizothrombin and factor Xa, validating previous biochemical studies
Clinical Relevance: This structural insight into thrombin generation could inform development of more targeted anticoagulants or procoagulant therapies for bleeding disorders managed in UK haematology services.
Limitations: The study used a truncated form of meizothrombin which may not fully represent the native activation process.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Impact of intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine, and their combination on infant outcomes: A randomized controlled trial
Nankabirwa JI, Kakuru A, Nguyen AT et al. · 2026 Apr 20
Study Type: Randomized controlled trial
Key Question: Do different intermittent preventive treatment regimens for malaria in pregnancy affect infant outcomes up to 12 months of age?
Key Findings: - Clinical malaria incidence in infants was similar across all three maternal treatment groups (IPTp-SP, IPTp-DP, and IPTp-DP+SP), with incidence rate ratios of 1.04 and 0.93 respectively compared to IPTp-SP
- Infants born to mothers receiving dihydroartemisinin-piperaquine (alone or combined) had higher prevalence of wasting at birth (RR 2.25-2.30) compared to sulfadoxine-pyrimethamine
- Growth differences resolved by 3-6 months of age with no long-term impact on infant development
Clinical Relevance: This evidence supports that while IPTp-DP may cause transient neonatal growth effects, it does not compromise long-term infant health outcomes, relevant for UK clinicians advising pregnant women travelling to malaria-endemic areas.
Limitations: Study conducted in a single high-transmission setting, limiting generalisability to different malaria transmission intensities.
Critical care (London, England)
EEG for bedside monitoring: the intensivist's point of view
Taccone FS, Ozkaya T, Baggiani M et al. · 2026 Apr 17
Study Type: Commentary
Key Question: How can EEG monitoring be better integrated into routine ICU practice for critically ill patients with acute brain injury?
Key Findings: - EEG remains underutilised in ICU despite being safe, non-invasive and relatively inexpensive
- Implementation barriers include lack of continuous monitoring capacity for all patients and dependence on specialised personnel for interpretation
- Successful integration requires tailored EEG montages for specific clinical questions and stratified information presentation adapted to different healthcare professional expertise levels
Clinical Relevance: This addresses a key gap in UK ICUs where EEG monitoring could enable earlier detection of reversible brain insults and seizures, potentially improving outcomes for patients with acute brain injury through multimodal monitoring approaches.
Limitations: As a commentary rather than original research, it provides expert opinion but lacks empirical evidence to support the proposed implementation strategies.
American journal of kidney diseases : the official journal of the National Kidney Foundation
Risks of Hypocalcemia and Other Bone Mineral Disorders for Denosumab Versus Zoledronate Across the Spectrum of Kidney Function: A Target Trial Emulation
Xiao R, Faucon AL, He N et al. · 2026 Apr 18
Study Type: Observational cohort study with active comparator (target trial emulation)
Key Question: Does denosumab versus zoledronate carry different risks of hypocalcaemia and bone mineral disorders across varying levels of kidney function?
Key Findings: - Denosumab increased hypocalcaemia risk vs zoledronate (HR 2.10, 95% CI 1.28-4.33; absolute risk difference 0.72%), with events occurring mainly within first two weeks
- Risk differences were substantially higher in patients with eGFR <60 mL/min/1.73m² compared to those with eGFR ≥60: hypocalcaemia (2.12% vs 0.19%) and secondary hyperparathyroidism (4.84% vs 0.03%)
- Similar patterns observed for hypophosphataemia, though interaction with eGFR was less pronounced
Clinical Relevance: UK nephrology services should implement enhanced biochemical monitoring protocols for CKD patients receiving denosumab, particularly those with eGFR <60 mL/min/1.73m², given substantially elevated risks of clinically significant bone mineral disorders.
Limitations: Observational design with potential residual confounding and limited generalisability beyond Swedish healthcare setting.
Annals of neurology
Developing a Virtual Research Environment in the Parkinson's Progression Markers Initiative: myPPMI
Stanley CE, Fabrizio K, McMahon BA et al. · 2026 Apr 21
Study Type: Technology development/implementation study
Key Question: How can a virtual research environment enhance participant engagement and data collection efficiency in Parkinson's disease research?
Key Findings: - myPPMI platform integrates education, screening, e-consent, motor/non-motor assessments, and biospecimen referral into a single virtual environment
- Platform enables precision recruitment with real-time eligibility matching and standardized low-burden data capture across multiple studies
- Cloud-native architecture supports multi-country deployment with daily analytics and tiered support model
Clinical Relevance: This virtual research framework could inform development of similar platforms for UK neurological research, potentially improving patient recruitment and reducing research participation burden within NHS trusts.
Limitations: No quantitative outcomes or comparative effectiveness data provided to assess platform performance versus traditional research methods.
Acta neurochirurgica
History and evolution of the far-lateral approach in neurosurgery
Hasen MA, de Lotbiniere-Bassett M, Couldwell WT · 2026 Apr 20
Study Type: Narrative review
Key Question: How has the far-lateral approach (FLA) evolved as a surgical technique for accessing the craniovertebral junction and foramen magnum region?
Key Findings: - The FLA developed from early limitations of midline posterior and transoral approaches, which caused significant brainstem retraction and high complication rates
- Technical refinements include consistent C1 posterior arch resection, selective condyle/jugular tubercle drilling, and endoscope-assisted visualization to improve exposure while preserving neurovascular structures
- Three main anatomical variants (transcondylar, supracondylar, paracondylar) provide modular exposure options tailored to specific lesion locations and pathology types
Clinical Relevance: UK neurosurgeons managing skull base pathology should understand FLA evolution and variants, as this approach offers superior access to ventrolateral craniovertebral junction lesions with lower complication rates than traditional approaches.
Limitations: This is a narrative review without systematic methodology or quantitative analysis of outcomes data.
American journal of obstetrics and gynecology
Reducing the long-term impact of cesarean scar defects: a focus on prevention
Walker SP, Bartels HC, Jurkovic D et al. · 2026 Apr 20
Study Type: Narrative review
Key Question: How can optimized cesarean section surgical techniques reduce the formation and long-term complications of cesarean scar defects?
Key Findings: - Emerging evidence suggests unlocked, interrupted, purse-string, and endometrium-free sutures with monofilament or barbed materials may reduce scar formation compared to continuous locked techniques
- Surgical repair of existing scar defects improves chronic gynecological symptoms and subfertility outcomes
- Evidence for preventing obstetric complications through scar repair remains limited, with theoretical concerns about increasing dehiscence/rupture risk
Clinical Relevance: With rising cesarean rates, UK obstetricians need evidence-based surgical techniques to prevent long-term complications including abnormal placentation, subfertility, and chronic pelvic pain that burden both patients and NHS resources.
Limitations: Substantial heterogeneity in existing studies regarding techniques, outcome measures, and follow-up prevents definitive surgical recommendations.
Annals of oncology : official journal of the European Society for Medical Oncology
Including tumor-infiltrating lymphocytes into the PREDICT prognostic model for triple-negative breast cancer survival
Wang Y, Drubay D, Jonas SF et al. · 2026 Apr 21
Study Type: Retrospective cohort study with model development and internal-external validation
Key Question: Can incorporating stromal tumor-infiltrating lymphocytes (sTILs) into the PREDICT prognostic model improve chemotherapy decision-making for women with early-stage triple-negative breast cancer?
Key Findings: - PREDICT_sTILs demonstrated good calibration (O/E ratios 0.98-0.99) and discrimination (AUC 0.74) at 5 and 10 years in 3698 TNBC patients
- Compared to standard PREDICT, the enhanced model identified 19-60 additional net true low-risk patients per 1000 chemotherapy-naïve patients at 10-year mortality risk thresholds of 8-15%
- Model particularly improved identification of low-risk patients who could safely avoid chemotherapy
Clinical Relevance: This could help UK oncologists make more personalised chemotherapy decisions in early-stage TNBC, potentially sparing some patients unnecessary treatment toxicity while maintaining prognostic accuracy.
Limitations: Retrospective design with patients diagnosed over a 38-year period may not reflect contemporary treatment practices and outcomes.
American journal of ophthalmology
Validation of the "FIRST-ROP" Algorithm at a Neonatal Intensive Care Unit Tertiary Center over Three Decades
Malek DA, Altamirano F, Chaaya C et al. · 2026 Apr 17
Study Type: Retrospective diagnostic comparison study
Key Question: Can the FIRST-ROP algorithm safely defer initial ROP screening to 34 weeks postmenstrual age in medium-risk preterm infants (≥27 weeks gestation, ≥800g birth weight)?
Key Findings: - Among 3,641 medium-risk infants over 30 years, no cases requiring treatment occurred before 34 weeks PMA, with median treatment age at 40.0 weeks (IQR 37.1-41.4)
- FIRST-ROP algorithm reduced screening examinations by 17% per patient compared to standard protocols (p<0.001)
- Algorithm maintained 100% sensitivity for treatment-warranted ROP detection (95% CI 99.3-100%)
Clinical Relevance: This large-scale validation supports adopting delayed ROP screening protocols in medium-risk infants, potentially reducing healthcare burden and infant stress in UK neonatal units while maintaining safety.
Limitations: Single-centre retrospective study may limit generalisability to other populations and healthcare systems.
Clinical orthopaedics and related research
S1P Modulation via S1P Lyase Inhibition Enhances Bone Regeneration in a Murine Critical-size Defect Model of Atrophic Nonunion
Reinkemeier F, Korte R, Bakri A et al. · 2026 Apr 08
Study Type: Experimental animal study (murine model)
Key Question: Does systemic S1P lyase inhibition enhance bone regeneration in a critical-size bone defect model of atrophic nonunion?
Key Findings: - DOP treatment significantly increased histologic bone formation (80,000 vs 52,000 pixels, p=0.03) and micro-CT bone volume (20.6% vs 8.8%, p=0.004) compared to controls
- Enhanced osteoblast differentiation markers (RUNX2 and osteocalcin both p<0.01) and increased osteoclast activity, indicating active bone remodeling
- Improved cellular proliferation and angiogenesis (PECAM-1 expression 23,000 vs 13,700, p=0.009)
Clinical Relevance: This preclinical work identifies S1P modulation as a potential non-invasive adjunctive therapy for managing atrophic nonunions, which currently have limited treatment options beyond revision surgery in NHS practice.
Limitations: Murine model findings require validation in large animal studies and clinical trials to establish optimal dosing, duration, and safety profile in humans.
JAMA pediatrics
First Antibiotic Prophylaxis Prescription Among Children With Sickle Cell Disease
Shi JS, LaFon E, Sutaria A et al. · 2026 Apr 20
Study Type: Insufficient information provided - abstract content not included.
Key Question: Cannot be determined from the title alone, though this appears to examine antibiotic prophylaxis prescribing patterns in paediatric sickle cell disease patients.
Key Findings: - No abstract provided - unable to determine specific findings
- Study appears to focus on first antibiotic prophylaxis prescriptions in children with sickle cell disease
- No data available on outcomes, prescribing patterns, or clinical results
Clinical Relevance: Antibiotic prophylaxis timing and prescribing practices are clinically important for UK paediatric sickle cell patients, as these children require pneumococcal prophylaxis from early infancy according to national guidelines.
Limitations: Cannot assess study limitations without access to the full abstract and methodology.
Note: This summary is incomplete as only the article title was provided. The abstract content would be needed to provide meaningful clinical insights about study design, sample size, outcomes, and clinical implications for UK paediatric practice.
BMJ supportive & palliative care
Informal caregiver burden and psychological distress among primary family caregivers of patients who had a stroke
Yılmaz S, Dalkıran B · 2026 Apr 22
Study Type: Cross-sectional descriptive study
Key Question: What is the burden and psychological distress experienced by primary family caregivers of hospitalised stroke patients, and what factors influence these outcomes?
Key Findings: - 294 stroke caregivers (54.4% female) showed medium caregiver burden (mean score 69.38±12.21) but high psychological distress (mean score 24.28±9.76)
- Strong correlation found between caregiver burden and psychological distress levels
- Gender and socioeconomic status affected burden; age, education, children number, socioeconomic status, and marital status influenced distress
Clinical Relevance: This identifies stroke caregivers as a high-risk group for psychological distress in acute hospital settings, highlighting the need for systematic caregiver assessment and support interventions that could be integrated into NHS stroke pathways.
Limitations: Cross-sectional design prevents determination of causality between burden, distress, and associated factors.
Histopathology
Glomerular plasmalemma vesicle-associated protein-1 as an endothelial remodelling marker complementing C4d in chronic active antibody-mediated rejection
Igarashi Y, Shimokawa M, Kawanishi K et al. · 2026 Apr 21
Study Type: Retrospective cohort study
Key Question: Does glomerular plasmalemma vesicle-associated protein-1 (PV-1) complement C4d staining in identifying active endothelial injury in chronic active antibody-mediated rejection?
Key Findings: - Analysis of 429 caABMR biopsies showed PV-1 specifically identifies endothelial remodelling (particularly in double-contour lesions) while C4d reflects cumulative complement activation
- PV-1 demonstrated dynamic reduction following B-cell-directed therapy, whereas C4d showed persistent staining in ABO-incompatible grafts
- In multivariable Cox models, changes in PV-1 (ΔPV-1) remained independently associated with death-censored graft survival, while changes in C4d (ΔC4d) did not
Clinical Relevance: Combined PV-1 and C4d assessment could refine histopathological evaluation of renal transplant biopsies by capturing distinct aspects of microvascular pathology and potentially improving monitoring of treatment response in antibody-mediated rejection.
Limitations: Retrospective design limits ability to establish causality and standardise treatment protocols across the study period.
Aesthetic surgery journal
Effect of Botulinum Toxin Injection Intervals on the Irreversibility of Targeted Muscle Paralysis: An Electromyographic Study
Ahmed MB, Al Aloosi M, Cohen JA et al. · 2026 Apr 21
Study Type: Randomized controlled trial
Key Question: Does prolonged short-interval botulinum toxin A administration to glabellar muscles induce irreversible or semi-permanent paralysis as measured by electromyography?
Key Findings: - 21 women received BoNT-A injections (20U) at 6-, 9-, or 12-week intervals for 108 weeks, with 48-week follow-up
- All groups showed sustained EMG suppression that persisted 48 weeks after treatment cessation, remaining well below baseline levels
- Shorter injection intervals (6-9 weeks) demonstrated greater sustained chemodenervation effect compared to 12-week intervals
Clinical Relevance: This suggests that frequent BoNT-A treatments may produce longer-lasting effects than traditional 3-4 month intervals, potentially reducing treatment frequency and costs for aesthetic patients in UK practice.
Limitations: Small sample size (21 patients) limits generalizability and requires larger studies with longer follow-up to confirm clinical significance of these electrophysiological findings.
JAMA psychiatry
Dialectical Behavior Therapy vs Schema Therapy for Patients With Borderline Personality Disorder: The BOOTS Multicenter Randomized Clinical Trial
Wibbelink CJM, Kamphuis JH, Sinnaeve R et al. · 2026 Apr 22
Study Type: Multicenter randomized controlled trial
Key Question: How does dialectical behavior therapy (DBT) compare to schema therapy (ST) for effectiveness in treating borderline personality disorder?
Key Findings: - No significant difference between DBT and ST in reducing BPD severity over 3 years (p=0.27, Cohen's d=0.15, 95% CI -0.17 to 0.47)
- Both treatments showed large, substantial improvements across all outcome measures including BPD symptoms, functioning, and quality of life
- Dropout rates were similar between groups (DBT: 52% at 2 years; ST: 46% at 2 years)
Clinical Relevance: This provides robust evidence that both DBT and ST are equally effective for BPD treatment, giving UK clinicians flexibility in choosing between these evidence-based approaches based on patient preferences, therapist expertise, or service capacity.
Limitations: High dropout rates (approximately 50% at 2 years) limit the generalizability of findings and reflect real-world treatment challenges in BPD populations.
American journal of public health
Challenges and Opportunities in Estimating the Mortality Burden Related to Heat Exposure: Maricopa County, Arizona, 2019-2023
Leahy HL, Vaidyanathan A, Hondula DM et al. · 2026 Apr 23
Study Type: Retrospective analysis using distributed lag nonlinear modelling
Key Question: What is the mortality burden attributable to heat exposure during Arizona's heat season, and how does this compare to routine surveillance estimates?
Key Findings: - At 99°F (95th percentile temperature), all-cause mortality increased by 11% (95% CI: 7-16%) compared to 77°F baseline
- Statistical modelling attributed 3,036 deaths (95% empirical CI: 968-4,887) to heat exposure over 2019-2023
- Heat-attributable deaths were 57% higher than those identified through standard epidemiological surveillance methods
Clinical Relevance: Demonstrates that routine heat surveillance significantly underestimates mortality burden, suggesting UK heat-health warning systems may similarly undercount heat-related deaths and miss opportunities for preventive interventions.
Limitations: Limited to one US county with extreme heat conditions, potentially limiting generalisability to UK climate and population characteristics.
AJR. American journal of roentgenology
Interreader Agreement for Individual Ancillary Features in LI-RADS CT/MRI Version 2018: A Systematic Review and Meta-Analysis
Jung YJ, Choi SH, Heo S et al. · 2026 Apr 22
Study Type: Systematic review and meta-analysis
Key Question: What is the interreader agreement for individual ancillary features in LI-RADS CT/MRI version 2018?
Key Findings: - Analysis of 47 studies (11,891 patients, 13,695 observations) showed variable agreement across 18 reported ancillary features, with kappa values ranging from 0.26 to 0.84
- Features favouring malignancy demonstrated higher agreement (kappa 0.58-0.84) than those favouring benignity (kappa 0.26-0.73)
- Enhancement paralleling blood pool showed poorest agreement (kappa 0.26), while hepatobiliary-phase hypointensity showed best agreement (kappa 0.84)
Clinical Relevance: This evidence highlights significant interpretation variability in LI-RADS ancillary features that UK radiologists rely upon for hepatocellular carcinoma diagnosis, potentially impacting diagnostic confidence and patient management decisions.
Limitations: Three ancillary features were not reported in any included studies, limiting the comprehensiveness of the agreement assessment.
Chest
Effects of antifungal treatment in COVID-19-associated pulmonary aspergillosis: A European multicenter cohort study
Reizine F, Feys S, Seidel D et al. · 2026 Apr 17
Study Type: Multicenter retrospective cohort study
Key Question: Is antifungal treatment associated with lower 60-day mortality in patients with probable or proven COVID-19-associated pulmonary aspergillosis (CAPA)?
Key Findings: - Among 259 CAPA patients, antifungal treatment was associated with significantly reduced 60-day mortality (weighted HR 0.28, 95% CI: 0.13-0.58, p<0.001)
- 91.5% received antifungals (mostly azoles), with baseline characteristics similar between treated and untreated groups
- Age, immunosuppressive treatment, and remdesivir were independently associated with increased mortality, while male sex and antifungal treatment reduced mortality risk
Clinical Relevance: This provides the largest evidence base to date supporting antifungal treatment for CAPA, reinforcing the importance of active screening and early treatment in UK ICUs managing COVID-19 patients, particularly immunocompromised individuals.
Limitations: Retrospective design with potential unmeasured confounding factors affecting treatment allocation decisions.
Annals of the rheumatic diseases
The evolving landscape of complement therapeutics in rheumatology
Holers VM · 2026 Apr 18
Study Type: Narrative review
Key Question: What is the current evidence for complement-targeted therapies in rheumatological diseases, particularly ANCA-associated vasculitis and rheumatoid arthritis?
Key Findings: - In ANCA-associated vasculitis, oral C5a receptor antagonists demonstrated substantial corticosteroid-sparing effects with initial clinical benefit
- In rheumatoid arthritis, C5 and C5aR1 inhibitors showed only modest benefit despite strong biomarker and preclinical evidence
- Both diseases appear driven by complement alternative pathway C5a generation causing target organ damage
Clinical Relevance: UK rheumatologists should be aware of emerging complement therapeutics, particularly for ANCA-associated vasculitis where steroid-sparing strategies are clinically valuable and could reduce long-term treatment burden.
Limitations: This narrative review format limits systematic assessment of evidence quality and may reflect author selection bias in study inclusion.
BJU international
Deep learning for fluorescence confocal microscopy image interpretation in radical prostatectomy
Fang L, Mayor N, Light A et al. · 2026 Apr 19
Study Type: Prospective deep learning model development and validation study
Key Question: Can a deep learning model accurately interpret fluorescence confocal microscopy images for real-time surgical margin assessment during radical prostatectomy?
Key Findings: - Internal validation (n=57): sensitivity 87.5%, specificity 97.9%, AUC 0.93 for detecting positive margins
- External validation (n=46): sensitivity 91.3%, specificity 73.9%, AUC 0.83, demonstrating generalisability across centres
- Model provides interpretable predictions in <2 seconds with visual explanations via Grad-CAM mapping
Clinical Relevance: This technology could enable real-time intraoperative margin assessment during radical prostatectomy without requiring immediate frozen section pathology support, potentially improving surgical outcomes whilst reducing theatre delays.
Limitations: Small dataset with only 275 total images and pronounced class imbalance (37 tumour vs 238 benign images) limits model robustness.