Churg‐Strauss syndrome with poor‐prognosis factors: A prospective multicenter trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in forty‐eight patients

Objective

To compare long and short durations of adjunctive cyclophosphamide for the treatment of severe Churg‐Strauss syndrome (CSS).

Methods

In this prospective multicenter therapeutic trial, 48 patients with CSS with at least 1 poor‐prognosis factor at baseline were treated with glucocorticoids and either 12 or 6 intravenous cyclophosphamide pulses.

Results

At 8 years, complete remission rates and severe side effects of therapy were comparable for both groups. The overall difference in relapses was not significant between the 12‐pulse and the 6‐pulse regimens (P = 0.07), but when considering only the number of mild relapses this difference became statistically significant (P < 0.02). Although the total number of inclusions was not reached, the study was stopped prematurely in response to the superiority of the 12‐pulse regimen.

Conclusion

We concluded that 12 cyclophosphamide pulses were better able to control severe CSS than a 6‐pulse regimen. The optimal duration of therapy remains to be determined.     

Correction to: Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review

Journal of Neurology - The original version of this article unfortunately contained a mistake. Fifth sentence of the fourth paragraph in the section “Non-nAChR autoantibody targets in...     

Suicidal behaviours in the peripartum period: a systematic scoping review of data linkage studies

Archives of Women's Mental Health - The purpose of this scoping review was to summarize research that uses linked data to examine peripartum suicidal behaviours and critically appraise studies...     

The UBIAD1 Prenyltransferase Links Menaquione‐4 Synthesis to Cholesterol Metabolic Enzymes

Schnyder corneal dystrophy (SCD) is an autosomal dominant disease characterized by germline variants in UBIAD1 introducing missense alterations leading to deposition of cholesterol in the cornea, progressive opacification, and loss of visual acuity. UBIAD1 was recently shown to synthesize menaquinone‐4 (MK‐4, vitamin K₂), but causal mechanisms of SCD are unknown. We report a novel c.864G>A UBIAD1 mutation altering glycine 177 to glutamic acid (p.G177E) in six SCD families, including four families from Finland who share a likely founder mutation. We observed reduced MK‐4 synthesis by UBIAD1 altered by SCD mutations p.N102S, p.G177R/E, and p.D112N, and molecular models showed p.G177‐mutant UBIAD1 disrupted transmembrane helices and active site residues. We show UBIAD1 interacts with HMGCR and SOAT1, enzymes catalyzing cholesterol synthesis and storage, respectively, using yeast two‐hybrid screening and immunoprecipitation. Docking simulations indicate cholesterol binds to UBIAD1 in the substrate‐binding cleft and substrate‐binding overlaps with GGPP binding, an MK‐4 substrate, suggesting potential competition between these metabolites. Impaired MK‐4 synthesis is a biochemical defect identified in SCD suggesting UBIAD1 links vitamin K and cholesterol metabolism through physical contact between enzymes and metabolites. Our data suggest a role for endogenous MK‐4 in maintaining cornea health and visual acuity.     

Hyperoxia in patients with cardiogenic shock after myocardial infarction supported with venoarterial extracorporeal membrane oxygenation

BackgroundVenoarterial extracorporeal membrane oxygenation (V-A ECMO) improves perfusion and oxygenation in patients with cardiogenic shock. However, it can also result in supranormal oxygen exposure. Recent evidence suggests hyperoxia may be harmful, particularly in critically ill patients. The aim of this study was to describe oxygen exposure in patients receiving V-A ECMO after acute myocardial infarction and to investigate the association between hyperoxia and in-hospital mortality.Methods and designWe conducted a retrospective, cohort study of consecutive patients receiving V-A ECMO at a single tertiary level ECMO centre. We compared the mean and peak arterial oxygen tensions over the first 72 h after V-A ECMO initiation (n = 30) with those from a convenience sample of patients treated with an intra-aortic balloon pump (IABP) (n = 30) for cardiogenic shock.ResultsSixty patients admitted between January 2012 and March 2018 were included in the study. Patients on V-A ECMO had significantly higher arterial oxygen tensions during the first three days than those with an IABP, at 0–24 h; V-A ECMO: 286.51 mmHg (135.76) vs IABP: 103.48 mmHg (15.22), p < 0.01.Thirteen of 30 (44.8%) patients in the V-A ECMO cohort manifested extreme hyperoxia (PaO₂ ≥300 mmHg) in the first 24 hrs, compared with none in the IABP population. Within the V-A ECMO group, there was no significant association between extreme hyperoxia and in-hospital mortality (P = 0.19), duration of mechanical ventilation (P = 0.63), or troponin levels (P = 0.16) in the first 24 hrs.ConclusionSevere hyperoxia is common in patients receiving V-A ECMO after acute myocardial infarction, and this continues for at least 72 h. We found no association between extreme hyperoxia and clinical outcomes.     

Experience of targeting subsidies on insecticide-treated nets: what do we know and what are the knowledge gaps?

Widespread coverage of vulnerable populations with insecticide-treated nets (ITNs) constitutes an important component of the Roll Back Malaria (RBM) strategy to control malaria. The Abuja Targets call for 60% coverage of children under 5 years of age and pregnant women by 2005; but current coverage in Africa is unacceptably low. The RBM 'Strategic Framework for Coordinated National Action in Scaling-up Insecticide-Treated Netting Programmes in Africa' promotes coordinated national action and advocates sustained public provision of targeted subsidies to maximise public health benefits, alongside support and stimulation of the private sector. Several countries have already planned or initiated targeted subsidy schemes either on a pilot scale or on a national scale, and have valuable experience which can inform future interventions. The WHO RBM 'Workshop on mapping models for delivering ITNs through targeted subsidies' held in Zambia in 2003 provided an opportunity to share and document these country experiences. This paper brings together experiences presented at the workshop with other information on experiences of targeting subsidies on ITNs, net treatment kits and retreatment services (ITN products) in order to describe alternative approaches, highlight their similarities and differences, outline lessons learnt, and identify gaps in knowledge. We find that while there is a growing body of knowledge on different approaches to targeting ITN subsidies, there are significant gaps in knowledge in crucial areas. Key questions regarding how best to target, how much it will cost and what outcomes (levels of coverage) to expect remain unanswered. High quality, well-funded monitoring and evaluation of alternative approaches to targeting ITN subsidies is vital to develop a knowledge base so that countries can design and implement effective strategies to target ITN subsidies.     

Speech‐perception training for older adults with hearing loss impacts word recognition and effort

The current pupillometry study examined the impact of speech‐perception training on word recognition and cognitive effort in older adults with hearing loss. Trainees identified more words at the follow‐up than at the baseline session. Training also resulted in an overall larger and faster peaking pupillary response, even when controlling for performance and reaction time. Perceptual and cognitive capacities affected the peak amplitude of the pupil response across participants but did not diminish the impact of training on the other pupil metrics. Thus, we demonstrated that pupillometry can be used to characterize training‐related and individual differences in effort during a challenging listening task. Importantly, the results indicate that speech‐perception training not only affects overall word recognition, but also a physiological metric of cognitive effort, which has the potential to be a biomarker of hearing loss intervention outcome.