皇家自由医院

BACKGROUND:Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS:We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS:The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS:In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).

Postpartum haemorrhage (PPH) is common, affecting an estimated 13% of women having vaginal birth and 31% of women having caesarean birth. Successful management of PPH requires early and accurate diagnosis and effective treatment. A systematic review found that subjective visual estimation of blood loss misses 52% of PPH diagnoses at vaginal birth (pooled sensitivity 48%, 95% CI 44-53), and probably more at caesarean birth. The WHO-International Federation of Gynecology and Obstetrics-International Confederation of Midwives consolidated guidelines on PPH therefore recommend objective quantification of blood loss with products such as a calibrated blood collection drape. When supported by a robust implementation strategy and a first-response treatment bundle, objective measurement of blood loss and monitoring of vital signs has been shown to diagnose PPH accurately and early, and improve clinical outcomes. Refractory PPH can progress to life-threatening PPH, which should be managed by a multidisciplinary team providing aggressive resuscitation and targeted treatment. Saving the life of a woman with excessive postpartum bleeding is a race against time. The six delays to avoid are: (1) in the diagnosis (by use of objective cumulative blood loss measurement and early trigger criteria), (2) in the first-response treatment (by authorising midwives to administer all components of a standardised bundle of interventions), (3) in the escalation (by use of explicit escalation criteria and red flags), (4) in the use of temporising measures (eg, non-pneumatic anti-shock garment), (5) in the identification and targeted management of any specific causes of bleeding, and (6) in the provision of blood and blood products. Quick actions to avoid these delays can mean the difference between life and death for a woman with PPH.

This ENETS guidance paper, developed by a multidisciplinary working group, provides up-to-date and practical advice on the diagnosis and management of lung and thymic carcinoids, based on recent developments and study results. These recommendations aim to provide practical recommendations for the diagnosis, treatment and follow-up of these tumours, and pave the road for more standardised care for our patients expecting improved outcomes. This paper is structured on a question-answer format in order to address common dilemmas encountered in clinical practice, including controversial issues and areas of uncertainty, based on the best available evidence and expert opinion when good quality evidence is not available. Each recommendation will provide a level of evidence and grade of recommendation as per the GRADE system (adapted from the Infectious Disease Society of United States Public Health Service grading system).

Introduction Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in ‘spontaneous’ inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission.Methods and analysis REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination.Ethics and dissemination The protocol was approved by East Midlands—Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration number ISRCTN18217497.

OBJECTIVES:Nintedanib slows progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD), but its tolerability in this patient group is a potential concern. METHODS:This multicentre study evaluated tolerability and treatment-related interruptions in SSc-ILD patients receiving nintedanib. Factors associated with interruption were analysed by logistic regression, with multivariable adjustment for potential confounders. Fisher's exact test was used when complete separation precluded logistic regression. Cox regression assessed time to first interruption. Weight changes before and after treatment were compared using the Wilcoxon signed-rank test. RESULTS:Among 63 patients (mean age 56.5±13.8 years, 22% male), 76% received nintedanib 150 mg twice daily, the remainder 100 mg twice daily; 86% were on mycophenolate. Over a median 22.2-month follow-up (95% CI 18.1-26.2), 51% experienced nintedanib interruptions. Patient-reported reasons for treatment interruption included diarrhoea (33.3%), nausea/vomiting (20.6%), weight loss (9.5%) and reflux (1.6%). Older age (p< 0.03) and BMI <18.5 kg/m2 (p=0.024) were independently associated with interruption. BMI <18.5 kg/m2 was also independently linked to shorter time to interruption. Permanent discontinuation occurred in 20.6%, with no significant predictors identified. Weight loss in the 12±6 months after treatment initiation (mean 2.05 kg) was significantly greater than in the preceding 12±6 months (1.09 kg) (p=0.001). CONCLUSIONS:Adverse effects frequently led to treatment interruptions in SSc-ILD patients. Older age and lower BMI were predictors of interruption, while no clear predictors of permanent discontinuation were identified. Most patients resumed treatment, highlighting the need for close monitoring and supportive care to manage side effects and maintain treatment continuity.