Author Correction: A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Could conservative iron chelation lead to neuroprotection in amyotrophic lateral sclerosis?

Iron accumulation has been observed in mouse models and both sporadic and familial forms of Amyotrophic lateral sclerosis. Iron chelation could reduce iron accumulation and the related excess of oxidative stress in the motor pathways. However, classical iron chelation would induce systemic iron depletion. We assess the safety and efficacy of conservative iron chelation (i.e. chelation with low risk of iron depletion) in a murine preclinical model and pilot clinical trial. In Sod1G86R mice, deferiprone increased the mean life span as compared with placebo. The safety was good, without anemia after 12 months of deferiprone in the 23 ALS patients enrolled in the clinical trial. The decreases in the ALS Functional Rating Scale and the body mass index (BMI) were significantly smaller for the first 3 months of deferiprone treatment (30 mg/kg/day) than for the first treatment-free period. Iron levels in the cervical spinal cord, medulla oblongata and motor cortex (according to MRI), as well as cerebrospinal fluid levels of oxidative stress and neurofilament light chains were lower after deferiprone treatment. Our observation leads to the hypothesis that moderate iron chelation regimen that avoids changes in systemic iron levels may constitute a novel therapeutic modality of neuroprotection for ALS

Improving the wellbeing of caregivers of patients with COPD using a home-based pulmonary rehabilitation programme

Objectives The aim of this study was to evaluate the effects of a home-based pulmonary rehabilitation (PR) programme on anxiety and depressive symptoms, general fatigue and burden in informal caregivers of patients with COPD. We also evaluated the baseline characteristics of both patients and caregivers that contributed to the change in caregiver's outcomes after PR. Methods In this retrospective study, patients with COPD were referred to an 8-week home-based PR programme consisting of a weekly supervised 90-min session. Informal caregivers were invited to participate in PR according to the patient's preference and its availability. Caregivers received educational support, behavioural therapies and self-management strategies using the same methods as for patients. Burden, anxiety and depressive symptoms, and general fatigue of caregivers were assessed at baseline and at the end of PR. Results 241 patients with COPD and 138 (57.3%) caregivers were included. The majority of the caregivers were women (70.5%) and spouses (90.3%) and had at least three comorbidities (57.3%). A large proportion of caregivers showed baseline high burden, anxiety symptoms and abnormal fatigue (40%, 40% and 45%, respectively). Burden, anxiety and depressive symptoms, and general fatigue of informal caregivers were all improved after PR (p<0.05). Long-term oxygen therapy and/or noninvasive ventilation, coronaropathy and/or peripheral arterial disease and a higher baseline modified Medical Research Council Dyspnoea scale score in patients with COPD were associated with a decrease in caregiver's burden after PR. Conclusion A large proportion of caregivers of patients with COPD showed anxiety symptoms, fatigue and a high burden. These outcomes were improved by integrating the caregiver into a home-based PR programme

Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model.

In spinal cord injury, onset of detrusor overactivity (DO) is detrimental for quality of life (incontinence) and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques.To assess the efficacy of early fesoterodine fumarate (FF) administration in preventing bladder overactivity in a spinal cord transected (SCT) rat model.33 Sprague-Dawley rats were allocated to 6 groups-Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP), baseline pressure, threshold pressure (Pthres) and maximum pressure (Pmax). Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn's tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05.Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls.Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols

Activated Clotting Time Monitoring during Atrial Fibrillation Catheter Ablation: Does the Anticoagulant Matter?

Atrial fibrillation (AF) catheter ablation is performed in patients receiving direct oral anticoagulants (DOACs) with intra-procedural unfractionated heparin (UFH) administration to achieve activated clotting time (ACT) at 300 s, as for vitamin K antagonist (VKA). We determined whether ACT monitoring might be transposed from VKA to DOAC-treated patients. Blood was taken from 124 patients receiving uninterrupted dabigatran, rivaroxaban, apixaban, or VKA or being untreated. DOAC concentration or INR (VKA) were measured. ACT was determined at baseline, and after spiking with UFH doses equivalent to 1000, 2500, 5000 and 10000 IU in vivo. At baseline, anticoagulants prolonged ACT differently, ACT was longer with dabigatran and shorter with apixaban despite similar concentrations. ACT strongly correlated with INR and dabigatran concentration, but not with apixaban or rivaroxaban concentrations. Moreover, UFH effects on ACT prolongation depended on the anticoagulant: dose-response curves in samples with VKA and dabigatran were parallel whereas ACT prolongation in response to UFH was significantly smaller with rivaroxaban and especially apixaban. Therefore, UFH to achieve ACT at 300 s might be transposed from VKA to uninterrupted dabigatran-treated patients but not to patients receiving FXa-inhibitors, especially apixaban. Targeting 300 s might expose to UFH overdosing and bleeding, questioning the current anticoagulation strategy

Respiratory changes of the inferior vena cava diameter predict fluid responsiveness in spontaneously breathing patients with cardiac arrhythmias

Abstract Background Whether the respiratory changes of the inferior vena cava diameter during a deep standardized inspiration can reliably predict fluid responsiveness in spontaneously breathing patients with cardiac arrhythmia is unknown. Methods This prospective two-center study included nonventilated arrhythmic patients with infection-induced acute circulatory failure. Hemodynamic status was assessed at baseline and after a volume expansion of 500 mL 4% gelatin. The inferior vena cava diameters were measured with transthoracic echocardiography using the bi-dimensional mode on a subcostal long-axis view. Standardized respiratory cycles consisted of a deep inspiration with concomitant control of buccal pressures and passive exhalation. The collapsibility index of the inferior vena cava was calculated as [(expiratory–inspiratory)/expiratory] diameters. Results Among the 55 patients included in the study, 29 (53%) were responders to volume expansion. The areas under the ROC curve for the collapsibility index and inspiratory diameter of the inferior vena cava were both of 0.93 [95% CI 0.86; 1]. A collapsibility index ≥ 39% predicted fluid responsiveness with a sensitivity of 93% and a specificity of 88%. An inspiratory diameter < 11 mm predicted fluid responsiveness with a sensitivity of 83% and a specificity of 88%. A correlation between the inspiratory effort and the inferior vena cava collapsibility was found in responders but was absent in nonresponder patients. Conclusions In spontaneously breathing patients with cardiac arrhythmias, the collapsibility index and inspiratory diameter of the inferior vena cava assessed during a deep inspiration may be noninvasive bedside tools to predict fluid responsiveness in acute circulatory failure related to infection. These results, obtained in a small and selected population, need to be confirmed in a larger-scale study before considering any clinical application

Cystometric parameters–comparison of Group 2 to Group 1.

<p>Cystometric parameters–comparison of Group 2 to Group 1.</p

Maximum pressure (Groups 2–6).

<p>Pmax: Maximum pressure SCT control (Group 2): untreated SCT rats; FF 0.18 (Group 3): SCT rats treated with FF 0.18 mg/kg/day; FF 0.12 (Group 4): SCT rats treated with FF 0.12 mg/kg/day; FF 0.18 + WOP (Group 5): SCT rats treated with FF 0.18 mg/kg/day + 72-h wash-out period; FF 0.12 + WOP (Group 6): SCT rats treated with FF 0.12 mg/kg/day + 72-h wash-out period.</p

Intermicturition pressure (Groups 2–6).

<p>IMP: intermicturition pressure SCT control (Group 2): untreated SCT rats; FF 0.18 (Group 3): SCT rats treated with FF 0.18 mg/kg/day; FF 0.12 (Group 4): SCT rats treated with FF 0.12 mg/kg/day; FF 0.18 + WOP (Group 5): SCT rats treated with FF 0.18 mg/kg/day + 72-h wash-out period; FF 0.12 + WOP (Group 6): SCT rats treated with FF 0.12 mg/kg/day + 72-h wash-out period.</p