Abstract
Background
Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In ...March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxicity. No data are available regarding the toxicity of this treatment in haemodialysis patients.
Methods
We report the use of HCQ and AZI in a cohort of COVID-19 haemodialysis patients with focus on safety concerns.
Results
Twenty-one patients received 200 mg HCQ thrice daily during 10 days, and AZI 500 mg on Day 1, and 250 mg on the four following days. HCQ plasma concentrations were within the recommended range (0.1–1.0 µg/mL) in all patients except one, in which maximum concentration was 1.1 µg/mL. HCQ concentration raised until the third day and remained stable thereafter. No cardiac event occurred in spite of progressive lengthening of corrected QT interval (QTc) during the treatment. One patient experienced a long QTc syndrome (QTc >500 ms) without any arrhythmia episode, although HCQ concentration was in the target range. Five (23.8%) patients experienced hypoglycaemia, a well-known HCQ side-effect. SARS-CoV-2 RNA remained detectable in nasopharyngeal swabs for a long time in haemodialysis patients (mean time 21 days).
Conclusions
HCQ and AZI are safe in haemodialysis patients at these doses but can lead to long QTc syndrome and hypoglycaemia. HCQ concentrations were not correlated with side effects. We recommend monitoring of the QTc length throughout treatment, as well as glycaemia. SARS-CoV-2 could persist for longer in haemodialysis patients than in the general population.
The enteropathogen Shigella flexneri invades epithelial cells, leading to inflammation and tissue destruction. We report that Shigella infection of epithelial cells induces an early genotoxic stress, ...but the resulting p53 response and cell death are impaired due to the bacterium's ability to promote p53 degradation, mainly through calpain protease activation. Calpain activation is promoted by the Shigella virulence effector VirA and dependent on calcium flux and the depletion of the endogenous calpain inhibitor calpastatin. Further, although VirA-induced calpain activity is critical for regulating cytoskeletal events driving bacterial uptake, calpain activation ultimately leads to necrotic cell death, thereby restricting Shigella intracellular growth. Therefore, calpains work at multiple steps in regulating Shigella pathogenesis by disrupting the p53-dependent DNA repair response early during infection and regulating both formation and ultimate death of the Shigella epithelial replicative niche.
► Genotoxic stress and p53 response are induced early during Shigella epithelial infection ► Shigella virulence effector VirA activates calpain proteases in a Ca2+-dependent manner ► Calpain degrades p53 and impairs the DNA repair response and apoptotic cell death ► Calpain restricts Shigella intracellular proliferation by inducing late necrosis
During the 2009/10 pandemic, a national surveillance system for severe influenza cases was set up in France. We present results from the system's first four years. All severe influenza cases admitted ...to intensive care units (ICU) were reported to the Institut de Veille Sanitaire using a standardised form: data on demographics, immunisation and virological status, risk factors, severity (e.g. acute respiratory distress syndrome (ARDS) onset, mechanical ventilation, extracorporeal life support) and outcome. Multivariate analysis was performed to identify factors associated with ARDS and death. The number of confirmed influenza cases varied from 1,210 in 2009/10 to 321 in 2011/12. Most ICU patients were infected with A(H1N1)pdm09, except during the 2011/12 winter season when A(H3N2)-related infections predominated. Patients' characteristics varied according to the predominant strain. Based on multivariate analysis, risk factors associated with death were age ≥ 65 years, patients with any of the usual recommended indications for vaccination and clinical severity. ARDS occurred more frequently in patients who were middle-aged (36-55 years), pregnant, obese, or infected with A(H1N1)pdm09. Female sex and influenza vaccination were protective. These data confirm the persistent virulence of A(H1N1)pdm09 after the pandemic and the heterogeneity of influenza seasons, and reinforce the need for surveillance of severe influenza cases.
Home mechanical ventilation is classically used to treat neuromuscular patients with chronic respiratory insufficiency. Since the heart and lungs are localized in the thorax, intrathoracic pressure ...may directly affect heart function. Here, we report the direct cyclic effects of mechanical ventilation on the right and left ventricular systolic and diastolic function in serial cases. These cases highlight the importance of performing Doppler echocardiography in patients with neuromuscular disorders, focusing on the right and left ventricular systolic and diastolic functions in the context of ventilation setting modifications or introduction.
We report 2 cases of fatal rhabdomyolysis in children carrying an LPIN1 mutations preceded by similar electrocardiogram changes, including diffuse symmetrical high-amplitude T waves. Our report ...underlines the severity of this disease and the need for active management of episodes of rhabdomyolysis in a pediatric intensive care unit.
Kawasaki disease is an acute vasculitis, that has a classic complication of acquired coronary artery aneurysm. Severe forms with multi‐organ involvement or neurological dysfunction are rare. Cerebral ...vascular involvement has been related to large‐vessel injury or cardioembolism, leading to focal brain infarction. A 4‐year‐old female presented with unusual, rapidly catastrophic Kawasaki disease with refractory shock, acute renal failure, and coma, requiring intensive haemodynamic management. The observation of diffuse micro‐haemorrhages (T2*‐weighted sequence) associated with white matter injury on brain magnetic resonance imaging (MRI) pointed towards lesions of the medium/small blood vessels. Cerebral vasculitis was suspected and the immunosuppressive treatment was increased Subsequently, the patient’s recovery was rapid. On follow‐up severe, bilateral vitritis was evident and surgery improved visual outcome. Early recognition of severe or unusual forms of Kawasaki disease could lead to more favourable outcome using appropriate treatment strategies. Diffuse cerebral micro‐haemorrhages on T2* brain MRI sequences might be a key sign for the diagnosis of medium or small cerebral vessel involvement.
In cardiac surgery, patients are at risk of phrenic nerve injury, which leads to diaphragm dysfunction and acute respiratory failure. Diaphragm dysfunction (DD) is relatively frequent in cardiac ...surgery and particularly affects patients after coronary artery bypass graft. The onset of DD affects patients' prognosis in term of weaning from mechanical ventilation and hospital length of stay. The authors present a narrative review about diaphragm physiology, techniques used to assess diaphragm function, and the clinical application of diaphragm ultrasound in patients undergoing cardiac surgery.
Acute flaccid myelitis (AFM) is an acute paralysis syndrome defined by a specific inflammation of the anterior horn cells of the spinal cord. From 2014, worrying waves of life-threatening AFM ...consecutive to enterovirus infection (EV-D68 and EV-A71) have been reported. We describe 10 children displaying an AFM with an EV infection, the treatments performed and the 1 to 3-years follow-up. Two groups of patients were distinguished: 6 children ("
") had severe motor disability whereas 4 other children ("
") displayed severe brainstem weakness requiring ventilation support. Electrodiagnostic studies (
= 8) support the presence of a motor neuronopathy associated to myelitis. The best prognosis factor seems to be the motor recovery after the first 4 weeks of the disease.
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