Real‐life effectiveness of carfilzomib in patients with relapsed multiple myeloma receiving treatment in the context of early access: The CARMYN study

Abstract The real‐life retrospective observational study CARMYN aimed at investigating the long‐term efficacy and safety of carfilzomib in combination with dexamethasone and lenalidomide (KRd, 159 patients). These patients (62% in first and 38% in second relapse, median age 62 yo) were treated between 02/2014 and 02/2017. Most had been pre‐exposed to bortezomib (98.2%) and to an IMID (75.4%). At the time of collection, 90% had permanently discontinued carfilzomib. Data collection was conducted from January to July 2021 in 27 participating sites, after a median of 39 months follow‐up. For patients treated with KRd, an overall response rate of 78.4% translated in a median progression free survival (PFS) of 24.0 months (95% CI 18.8–27.6) and a median overall survival (OS) of 51.1 months (95% CI 41.3–not reached). Results were poorer but difficult to interpret in the small cohort of Kd recipients. The study is one of the longest real‐life studies of carfilzomib treatment in patients in first or second relapse. CARMYN confirmed the real‐life long‐term efficacy of carfilzomib in combination with lenalidomide and dexamethasone with results similar to those of clinical trials. The KRd regimen is thus an option to consider for late relapses in the current context of MM management

Effect of nasogastric versus orogastric tube placement on ventilator-associated pneumonia incidence in critically ill patients: a study protocol for a cluster randomised crossover trial in 16 intensive care units in France (SONG trial)

Introduction Patients in intensive care units (ICUs) frequently require mechanical ventilation, with approximately half needing invasive ventilation through an orotracheal tube. For these patients, gastric tube (GT) insertion is routinely performed to administer nutrition and medications or to drain gastric contents. The insertion route (oral or nasal) may affect the incidence of ventilator-associated pneumonia (VAP), a significant ICU care complication. This study aims to compare the impact of oral versus nasal GT insertion on the incidence of VAP in intubated ICU patients.Methods and analysis The SONG trial (NCT 05915663) is a multicentre, open-label, two-period, two-intervention, cluster randomised crossover superiority trial. 16 French ICUs will participate. ICUs will be randomised to periods of nasogastric or orogastric tube placement. The trial includes a practice standardisation period, followed by two 12-month inclusion periods separated by a monitoring and washout period. The primary endpoint is the incidence rate of VAP at day 28, confirmed by three independent physicians. Secondary endpoints include the ease of GT insertion, measured by the number of attempts.Ethics and dissemination This study received approval from a central ethical review board on 12 April 2024 (CPP Sud-est VI, registration number 23.00943.000175). Patients are included after informed consent or, when not possible, from next of kin. If none are available, the investigator will proceed with emergency inclusion, following French law. When consent is initially obtained from the next of kin or through emergency inclusion, the investigator will seek consent from the patient as soon as possible. Data will be anonymised and patient confidentiality maintained. Results will be published in peer-reviewed journals and presented at scientific meetings.Trial registration number NCT05915663

Mean arterial pressure after out-of-hospital cardiac arrest (METAPHORE): study protocol for a multicentre controlled trial with blinded primary outcome assessor

International audienceneurological, cutaneous, digestive and haemorrhagic complications within 7 days after inclusion). Subgroup analyses are planned according to initial cardiac arrest rhythm (shockable or non-shockable), chronic hypertension and Cardiac Arrest Hospital Prognosis score. Outcomes will be analysed on an intention-to-treat basis. Recruitment started in October 2024 in 27 French ICUs, and a sample of 1380 patients is expected by October 2027. Ethics and disseminationThe study received approval from the national ethics review board on 8 February 2024 (Comité de Protection des Personnes Sud-Est V -2023-A00257-38). Patients are included after informed consent has been obtained either from a proxy or through an emergency procedure. Results will be submitted for publication in peerreviewed journals. Trial registration number ClinicalTrials. gov: NCT05486884.</div

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case–control study

Background Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM).Objectives To assess the significance of DH/BS in patients with IM.Methods Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1.Results 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p&lt;0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p&lt;0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p&lt;0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p&lt;0.05).Conclusion In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis)

Mean arterial pressure after out-of-hospital cardiac arrest (METAPHORE): study protocol for a multicentre controlled trial with blinded primary outcome assessor

Introduction Out-of-hospital cardiac arrest is a public health concern with a high mortality rate. Hypoxic ischaemic brain injury is the primary cause of death in patients admitted to the intensive care unit (ICU) after return of spontaneous circulation (ROSC). Several systemic factors, such as hypotension, can exacerbate brain injuries. International guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg. Several observational studies suggest that a higher MAP may be associated with better outcomes, but no randomised trials have shown an effect of higher MAP. The ongoing METAPHORE (mean arterial pressure after out-of-hospital cardiac arrest) trial aims to compare a standard MAP threshold (MAP ≥65 mm Hg) with a high MAP threshold (MAP ≥90 mm Hg) to evaluate whether implementing a higher MAP threshold can improve neurological outcomes in patients admitted to ICU after cardiac arrest.Methods and analysis METAPHORE is a randomised, controlled, multicentre, open-label trial with a blinded primary outcome assessor, comparing two parallel groups of patients 18 years of age or older, receiving invasive mechanical ventilation for coma defined by a Glasgow Coma Score ≤8/15 after out-of-hospital cardiac arrest and sustained ROSC. Eligible patients are randomly assigned in a 1:1 ratio to either a MAP target threshold of 65 mm Hg or higher throughout the ICU stay (control group) or a MAP target threshold of 90 mm Hg or higher during the first 24 hours after randomisation, followed by 65 mm Hg or higher for the remainder of the ICU stay (intervention group). Both groups receive the same general care concerning post-cardiac arrest syndrome management according to international guidelines. The primary endpoint is the proportion of patients with a favourable neurological outcome as defined by a modified Rankin scale (mRS) of 0 to 3 measured on day 180 after inclusion by a psychologist blinded to the allocation of the intervention. Secondary outcomes are the proportion of patients alive at ICU and hospital discharge, at day 28 and day 180; proportion of patients alive at ICU discharge with a mRS of 0 to 3; the EuroQOL-5D-5L at day 180; the Clinical Frailty Scale at day 180; the number of ICU-free days, ventilator-free days, catecholamine-free days and renal replacement therapy-free days at day 28; the proportion of patients with acute kidney injury stage 3 and need for renal replacement therapy within ICU stay and proportion of patients with persistent need for renal replacement therapy at ICU discharge; and safety outcomes (cardiovascular, neurological, cutaneous, digestive and haemorrhagic complications within 7 days after inclusion). Subgroup analyses are planned according to initial cardiac arrest rhythm (shockable or non-shockable), chronic hypertension and Cardiac Arrest Hospital Prognosis score. Outcomes will be analysed on an intention-to-treat basis. Recruitment started in October 2024 in 27 French ICUs, and a sample of 1380 patients is expected by October 2027.Ethics and dissemination The study received approval from the national ethics review board on 8 February 2024 (Comité de Protection des Personnes Sud-Est V – 2023-A00257-38). Patients are included after informed consent has been obtained either from a proxy or through an emergency procedure. Results will be submitted for publication in peer-reviewed journals.Trial registration number ClinicalTrials.gov: NCT05486884

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup