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Objective: Current treatments for Friedreich's ataxia, a neurodegenerative disorder characterized by decreased intramitochondrial frataxin, do not address low frataxin concentrations. Nomlabofusp (previously CTI-1601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin deficiency. Phase 1 studies assessed the safety, pharmacokinetic, and pharmacodynamic profiles of subcutaneously administered nomlabofusp in adults with Friedreich's ataxia., Methods: Patients were enrolled in two Phase 1, double-blind, placebo-controlled studies. The single ascending-dose (SAD) study (NCT04176991) evaluated single doses of nomlabofusp (25, 50, 75, or 100 mg) or placebo. The multiple ascending-dose (MAD) study (NCT04519567) evaluated nomlabofusp (25 mg daily for 4 days then every third day, 50 mg daily for 7 days then every 2 days, or 100 mg daily) or placebo for 13 days., Results: Patients aged 19-69 years were enrolled (SAD, N = 28; MAD, N = 27). Nomlabofusp was generally well tolerated through 13 days. Most adverse events were mild and resolved quickly. No serious adverse events or deaths were reported. Peak nomlabofusp plasma concentrations occurred 15 min after subcutaneous administration. Nomlabofusp plasma exposures increased with increasing doses and daily administration and decreased with reduced dosing frequency. Increased frataxin concentrations were observed in buccal cells, skin, and platelets with higher and more frequent nomlabofusp administration., Interpretation: Results from this study support a favorable safety profile for nomlabofusp. Subcutaneous nomlabofusp injections were quickly absorbed; higher doses and daily administration resulted in increased tissue frataxin concentrations. Future studies will evaluate longer-term safety and possible efficacy of nomlabofusp., (© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: To correct with post-processing effects of incomplete recovery of the longitudinal magnetization before a new inversion pulse in the Modified Look-Locker Inversion recovery sequence (MOLLI) sequence., Theory and Methods: We model such effects as a temporal shift ([Formula: see text]) of the signal of the Look-Locker block following next inversion pulses. After using the following equation [Formula: see text], a temporal registration of [Formula: see text] is applied to the signal of the affected block to adjust the sampling time of the recovery signal and correct the underlying effect on quantitative T1. To test our approach, simulations, phantoms, and five volunteers' data were used while applying different MOLLI sampling schemes at different heart rates and compared to the reference three-parameter fit., Results: The temporal registration of the affected signals allows to reach higher accuracy on long T1 when compared to the reference three parameters fit (10.15 vs 22.12% for T1 = 1785 ms; 8.22 vs 14.65% for T1 = 1278 ms), and lower average variation in case of rest-period deletion (62 vs 231 ms)., Conclusion: The proposed approach leads to more accurate T1 in case of incomplete recovery. It is less sensitive to parameters affecting the recovery such as the rest period or the sampling scheme; and, therefore, supports multi-center studies with different MOLLI protocols.

Background : In Reunion Island, influenza is not considered a serious illness despite significant mortality in intensive care unit (ICU). We assess the post-pandemic mortality of influenza by comparing it to other community-acquired pneumonia in our ICU. Methods : Retrospective, descriptive, and single-centre cohort study. The main aim was to determine the standardized mortality ratio (SMR) for influenza based on the quartiles of the SAPSII score in the reference population of 954 patients hospitalized for community-acquired pneumonia. Another aim was to analyze the risk factors for mortality in influenza patients. Results : 127 consecutive patients were hospitalized in our ICU with a positive influenza PCR, from January 2013 to December 2017. The mortality rate of these patients was 31% (CI 95%: 23-39%). In patients hospitalized for community-acquired pneumonia, the SMR of patients with influenza was 1.24 (CI 95%: 0.89-1.70). At admission, thirty-nine patients (31%) had superinfections, in 17 caused by methicillin-susceptible Staphylococcus aureus . Need for renal replacement therapy (RR 2.53 [1.29-4.93]) or ECMO (RR 2.35 [1.16-4.74]) were associated with mortality. Twenty-four patients underwent ECMO, 17 with VV-ECMO. Conclusions : Mortality in patients with influenza pneumonia was higher than the expected mortality in community-acquired pneumonia. Although generally considered benign, influenza is a deadly infection in ICU patients in Reunion Island.

Rationale: Patients repatriated from foreign hospitals are sources of extensively drug-resistant (XDR) bacteria outbreaks. Thus, an individual benefit potential for the patient opposes a collective ecological risk potential. These ethical issues have not been well studied., Patient Concerns: We report the case of a 74-year-old patient repatriated from Mauritius to the French island of Reunion who presented mesenteric infarction evolving over several days, and who suffered a cardiac arrest before transfer., Diagnoses: In Reunion Island, a CT-scan revealed a multisegmental enlarged parietal enlargement associated with free peritoneal effusion and a suboccluded aspect of the superior mesenteric artery., Interventions: Surgical exploration showed a severe mesenteric infarction with peritonitis, and a resection of 120cm of the small intestine was conducted. This patient was infected with a vanA glycopeptide-resistant Enterococcus faecium and a carbapenem-resistant Klebsiella pneumoniae which produced carbapenemases NDM-1 and OXA-181, which required specific care and could have led to a local epidemic., Outcomes: The patient died after 9 days after being admitted to the ICU., Lessons: Repatriation of critically ill patients from abroad should be considered according to ethical criteria, evaluating, if possible, the expected benefits, and ecological risks incurred. Limiting unnecessary transfers could be an effective measure to limit the spread of XDR bacteria.

Background: Iatrogenic tracheal rupture is a rare but life-threatening complication. If suspected by clinical examination or chest radiograph, a computed tomography scan can confirm the diagnosis, but the criterion standard is a bronchoscopy. There is no consensus on its management., Case Report: A 52-year-old woman was intubated in a prehospital setting after cardiac arrest. A gradual appearance of subcutaneous emphysema was observed after intubation. A computed tomography scan revealed a complicated tracheal rupture, pneumomediastinum, and pneumothorax. The management was surgical. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intubation in emergency conditions increases the risk of tracheal rupture and a delay in management is an important prognostic factor., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Melioidosis is a disease caused by bacteria called B. pseudomallei. Infections can develop after contact with standing water. This disease can reach all the organs and especially the lungs. It is associated with a high mortality rate (up to 50%). Melioidosis is endemic in northern Australia and in Southeast Asia. Nevertheless, B. pseudomallei may be endemic in the Indian Ocean region and in Madagascar in particular, so clinicians and microbiologists should consider acute melioidosis as a differential diagnosis in the Indian Ocean region, in particular from Madagascar.

The authors describe three cases of severe accidental poisoning by plants used as part of a traditional treatment in Mayotte. The established, or suspected, toxicity of Thevetia peruviana (Yellow oleander), Cinchona pubescens (Red quinine-tree), Melia azaderach (Persian lilac, also called china berry) and Azadirachta indica (Neem), is discussed. The clinical presentation is cardiac (atrioventricular block) and well known for Thevetia and Cinchona intoxications. Neurological signs and multi-organ failure are found for Azadirachta and Melia. The identification of the plants is never easy, nor is the evidence of their accountability. In the three cases reported, no other cause than the traditional treatment has been found to explain the clinical presentation. The outcome was favorable in all cases. The authors emphasize the difficulties to investigate these accidents, the poor medical knowledge of these practices in tropical areas, and in Mayotte particularly. The need for cooperation with local botanists, familiar with traditional medicine, is also underlined.