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Psoriasis is a common, chronic, immune-mediated skin disease affecting more than 40 million individuals worldwide. Psoriasis, along with psoriatic arthritis, are part of a broader psoriatic disease spectrum, and present with inflammatory skin and musculoskeletal manifestations driven by shared genetic, environmental, and immunological mechanisms. Skin psoriasis presents with diverse clinical phenotypes, including chronic plaque psoriasis, guttate, palmoplantar, erythrodermic, and pustular forms. Beyond cutaneous manifestations, psoriasis is associated with a substantial psychosocial burden and a wide range of comorbidities, including mental health disorders and cardio-metabolic diseases. Key psoriasis risk factors include genetic polymorphisms (most notably HLA-C*06:02), obesity, and environmental factors such as trauma, infections, and specific medications. Advances in understanding the key role of the IL-23-IL-17 inflammatory axis and related immunogenetic pathways have redefined psoriasis as a complex immune disorder, leading to the development of highly effective targeted biologic and small-molecule therapies that modulate cytokine signalling and intracellular pathways, offering improved disease control across cutaneous and musculoskeletal domains.
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Coronary artery bypass grafting (CABG) is a common but invasive operation traditionally performed through a median sternotomy. Minimally invasive cardiac surgery (MICS) CABG via small thoracotomy might improve postoperative recovery, but randomised evidence has been scarce. We aimed to compare patient-reported recovery after MICS CABG versus sternotomy CABG in patients with multivessel coronary artery disease and to describe clinical and safety outcomes. MIST was an investigator-initiated, international, open-label, randomised controlled trial done at seven centres (four academic hospitals and three community hospitals) in Canada, India, China, Germany, the USA, and Japan. Patients referred to participating surgeons for CABG were eligible if they were aged 18 years or older; had angiographically confirmed multivessel coronary artery disease, defined as lesions of at least 70% stenosis in at least two major epicardial vessels and at least two separate coronary artery territories (left anterior descending artery, left circumflex artery, or right coronary artery) or left main coronary stenosis of 50% or more; and were suitable for coronary surgery both with sternotomy CABG and MICS CABG. Patients who were haemodynamically compromised, had contraindications to either approach, had had previous cardiac surgery, or required concomitant procedures were excluded. Eligible patients were randomly assigned (1:1) to MICS CABG or sternotomy CABG by a central, web-based system, stratified by centre, with block sizes of four and six. The primary endpoint was patient-reported physical recovery at 1 month, assessed by the 36-item Short Form Health Survey Physical Component Summary (SF-36 PCS) score. The primary analysis was by intention to treat; safety analyses were done according to treatment received. Missing 1-month questionnaire data were handled by multiple imputation. The trial was registered with ClinicalTrials.gov (NCT03447938), and is closed to recruitment. Between Aug 24, 2018, and Nov 26, 2024, 176 patients were enrolled, 170 of whom were randomly assigned to MICS CABG (n=86) or sternotomy CABG (n=84). The median age of patients was 67·0 years (IQR 61·0-72·0), 154 (91%) patients were male, and 16 (9%) were female. At 1 month after surgery, SF-36 PCS scores were significantly higher in the MICS CABG group than in the sternotomy CABG group (mean 45·1 [SD 8·0] vs 42·2 [9·1]; mean difference 2·9 [95% CI 0·3-5·5]; p=0·031). Clinical and safety follow-up at 1 month was complete in all patients; 12-month clinical and safety follow-up was complete in all except three patients in the sternotomy CABG group. Up to 12 months after surgery, there were no deaths or strokes in either group; one major adverse cardiac or cerebrovascular event occurred in the MICS CABG group before 1 month and none in the sternotomy CABG group. For selected patients with multivessel coronary artery disease, MICS CABG performed by experienced teams improved patient-reported physical recovery at 1 month compared with sternotomy CABG, with no apparent safety penalty through to 12 months. These findings support consideration of MICS CABG in appropriately selected patients treated by experienced teams, and further studies of implementation, recovery pathways, and long-term outcomes. Medtronic.
Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL. This open-label, randomised, phase 3 trial was conducted across 56 university and academic non-university hospitals with established transplantation facilities in five European countries. Eligible for inclusion were untreated, immunocompetent patients with B-cell PCNSL, aged 18-65 years regardless of Eastern Cooperative Oncology Group (ECOG) performance status, or 66-70 years with ECOG performance status 0-2. Pretreatment corticosteroids were permitted. Exclusion criteria included lymphoma manifestation outside the CNS, and congenital or acquired immunodeficiency. Patients received four cycles of MATRix induction (comprising rituximab, high-dose cytarabine, and thiotepa, in addition to high-dose methotrexate). Patients reaching at least partial response were randomly assigned (1:1) to two cycles of R-DeVIC (rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin) or HCT-ASCT with carmustine and thiotepa. The primary endpoint was progression-free survival, assessed in the full analysis set (excluding patients with major violations of entry criteria). The safety analysis set contained all randomised patients who initiated therapy. This study is registered with ClinicalTrials.gov (NCT02531841) and the EU Clinical Trials Register (EudraCT number 2012-000620-17). The study is completed. Between July 16, 2014, and Aug 31, 2019, 368 patients were enrolled. 346 (94%) patients started induction treatment, and 230 were randomly assigned; 229 patients were analysed (R-DeVIC group, n=115; HCT-ASCT group, n=114). After a median follow-up of 45·3 months, 3-year progression-free survival was significantly superior in the HCT-ASCT group (hazard ratio 0·43 [95% CI 0·27-0·68]; p=0·0003). The 3-year progression-free survival was 78% (95% CI 69-85) in the HCT-ASCT group compared with 51% (41-60) in the R-DeVIC group. The mean number of adverse events per patient was 9·3 (SD 4·4) in the R-DeVIC group and 14·6 (5·8) in the HCT-ASCT group. Fatal serious adverse events following consolidation treatment occurred in two patients in the R-DeVIC group (both acute myeloid leukaemia) and in five patients in the HCT-ASCT group (infections and infestations [n=4], pulmonary embolism [n=1]); all of these events apart from the pulmonary embolism were judged to be possibly related to treatment. In the largest randomised trial in untreated PCNSL to date, HCT-ASCT significantly improved progression-free and overall survival compared with non-myeloablative consolidation in patients who had completed induction treatment, establishing it as the preferred consolidation strategy in fit patients. German Federal Ministry of Research, Technology and Space; Swiss Cancer Research Foundation; and Riemser Pharma.
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Self-management approaches in people with Parkinson's disease (PD) have potential to improve patient outcomes and reduce complications leading to hospital admissions. We aimed to evaluate the clinical and cost-effectiveness of the UCL Live Well with Parkinson's toolkit, a facilitated self-management intervention for people with PD. This two-arm randomised controlled trial in England (Trial Registration: ISRCTN92831552) recruited community-dwelling people with PD from NHS sites and self-referral. They were randomly assigned to the intervention or treatment as usual (TAU), and assessed at baseline, 6- and 12-month follow-up. The primary outcome was the PDQ-39 score, a PD-specific health-related quality of life measure, at 12-months with planned subgroup analyses. Secondary outcomes included non-motor and motor activities of daily living (MDS-UPDRS part I&II), utility values and QALYs derived from the EQ-5D-5L, and total health and social care costs over 12-months. The economic evaluation was based on cost-utility analysis using cost per QALY. All assessors were blinded to group allocation. Analysis was by intention to treat. 166 participants were randomised to the intervention and 180 to TAU, with 12-month follow-up assessments available in 141 (84.9%) and 164 (91.1%), respectively. The primary endpoint (PDQ-39 score) was similar for patients in the intervention and TAU groups (-1.03; 95% CI (-3.03 to 0.97)). Subgroup analyses of PDQ-39 scores in underserved groups however favoured the intervention (-4.0; 95% CI (-6.8 to -1.1)). The combined MDS-UPDRS part I + II score was improved in the intervention compared to the TAU group (-2.61; 95% CI (-4.58 to -0.64)). QALYs were not different between groups (0.018; 95% CI (-0.006 to 0.042) but total health and social care costs over 12-months were lower in the intervention group compared to TAU (-£1282; 95% CI (-£2700 to -£118)), driven mainly by reduced unplanned hospital admissions. Adverse events were similar in both groups. The Live Well with Parkinson's intervention alongside TAU was 99% cost-effective compared to TAU at a decision threshold of £20,000 per QALY and 98% at £30,000. The UCL Live Well with Parkinson's toolkit did not significantly improve health-related quality of life scores overall but improved activities of daily living and reduced health-care costs in comparison to TAU, mainly through reduced unplanned hospital admissions. National Institute for Health and Care Research RP-PG-1016-20001.
Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021-30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). In 2023, there were 50·9 million (95% UI 46·1-56·1) road injury incident cases, 1·34 million (1·04-1·58) deaths, and 75·3 million (59·8-89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10-39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9-39·7) and mortality decreased by 32·3% (6·1-49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7-56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1-7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9-947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. Gates Foundation.
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Duchenne muscular dystrophy (DMD) is an X-linked genetic disease of skeletal and cardiac muscle that leads to loss of ambulation and premature death due to progressive myopathy and cardiomyopathy. Deramiocel, a heart-derived cellular therapy consisting of human allogeneic cardiosphere-derived cells, improved cardiac and skeletal muscle function in phase 1-2 studies of DMD. Our aim was to assess the efficacy and safety of deramiocel in advanced DMD and support the findings of HOPE-2. HOPE-3, a phase 3, multicentre, randomised (1:1), double-blind, placebo-controlled study, included participants aged 10 years or older with DMD. Investigational product was infused intravenously every 3 months in outpatient settings. Skeletal and cardiac function was evaluated at 12 months. The primary endpoint was total Performance of the Upper Limb 2.0 (PUL2.0) percentage change from baseline. The trial is registered with ClinicalTrials.gov (NCT05126758). Between June 22, 2022, and May 28, 2024, 139 participants were screened, of whom 106 were randomly assigned to deramiocel (n=54) or placebo (n=52), and included in the intention-to-treat population. The primary endpoint showed significant improvements in the deramiocel group versus placebo. For total PUL2.0, least-squares mean percentage change at 12 months favoured deramiocel by 4·55% (95% CI 0·47-8·63; p=0·029). The safety profile of deramiocel was similar to that of placebo. Deramiocel safely slows disease progression in advanced DMD, preserving skeletal muscle function. Administered quarterly in a simple outpatient regimen, deramiocel is a promising treatment for DMD, agnostic to the precise underlying genetic lesion. Capricor Therapeutics.
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