Leptospirosis followed by Kawasaki-like disease: case report from an adult Swiss patient and review of the literature

Kawasaki disease (KD) is a vasculitis that mostly occurs in children, but rare cases in adults have been reported. We describe the case of a 43-year-old Swiss male who developed symptoms compatible with KD 7 weeks after leptospirosis, which was presumably acquired after swimming in a creek in the Swiss Alps. We performed a literature review and identified 10 other cases (all in children), in which Kawasaki-like disease was diagnosed in the context of leptospirosis. Outcome was favourable in most cases, including our patient. This exceptional case demonstrates both the possibility of autochthonous cases of leptospirosis in Switzerland as well as a possible association of leptospirosis with Kawasaki-like disease

High-Flow Oxygen with Capping or Suctioning for Tracheostomy Decannulation

9 p.BACKGROUND When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS Basing the decision to decannulate on suctioning frequency plus continuous highflow oxygen therapy rather than on 24-hour capping trials plus intermittent highflow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.

A New Peptide Ligand for Targeting Human Carbonic Anhydrase IX, Identified through the Phage Display Technology

Carbonic anhydrase IX (CAIX) is a transmembrane enzyme found to be overexpressed in various tumors and associated with tumor hypoxia. Ligands binding this target may be used to visualize hypoxia, tumor manifestation or treat tumors by endoradiotherapy

Neuron-specific proteotoxicity of mutant ataxin-3 in C. elegans: rescue by the DAF-16 and HSF-1 pathways

The risk of developing neurodegenerative diseases increases with age. Although many of the molecular pathways regulating proteotoxic stress and longevity are well characterized, their contribution to disease susceptibility remains unclear. In this study, we describe a new Caenorhabditis elegans model of Machado–Joseph disease pathogenesis. Pan-neuronal expression of mutant ATXN3 leads to a polyQ-length dependent, neuron subtype-specific aggregation and neuronal dysfunction. Analysis of different neurons revealed a pattern of dorsal nerve cord and sensory neuron susceptibility to mutant ataxin-3 that was distinct from the aggregation and toxicity profiles of polyQ-alone proteins. This reveals that the sequences flanking the polyQ-stretch in ATXN3 have a dominant influence on cell-intrinsic neuronal factors that modulate polyQ-mediated athogenesis. Aging influences the ATXN3 phenotypes which can be suppressed by the nregulation of the insulin/insulin growth factor-1-like signaling pathway and activation of heat shock factor-1.This work was supported by grants from Fundacão Ciência eTecnologia (FCT) to P.M. (PTDC/SAU-GMG/64076/2006, PTDC/SAU-GMG/112617/2009, SFRH/BD/27258/2006 to A.T.C., UMINHO/BI/052/2010 to A.J. and SFRH/BD/51059/2010 to A.N.C.), from the National Ataxia Foundation to PM and from the National Institutes of Health (NIGMS, NIA and NINDS) to R.M. This work was also granted by the Hospital San Rafael (Coruna) with the Rafael Hervada prize on Biomedical Research (2010)

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders?A successful strategy for clinical research of rare diseases

BACKGROUND: To improve our understanding of urea cycle disorders (UCDs) prospectively followed by two North American (NA) and European (EU) patient cohorts. AIMS: Description of the NA and EU patient samples and investigation of the prospects of combined and comparative analyses for individuals with UCDs. METHODS: Retrieval and comparison of the data from 1095 individuals (NA: 620, EU: 475) from two electronic databases. RESULTS: The proportion of females with ornithine transcarbamylase deficiency (fOTC-D), particularly those being asymptomatic (asfOTC-D), was higher in the NA than in the EU sample. Exclusion of asfOTC-D resulted in similar distributions in both samples. The mean age at first symptoms was higher in NA than in EU patients with late onset (LO), but similar for those with early (</= 28 days) onset (EO) of symptoms. Also, the mean age at diagnosis and diagnostic delay for EO and LO patients were similar in the NA and EU cohorts. In most patients (including fOTC-D), diagnosis was made after the onset of symptoms (59.9%) or by high-risk family screening (24.7%), and less often by newborn screening (8.9%) and prenatal testing (3.7%). Analysis of clinical phenotypes revealed that EO patients presented with more symptoms than LO individuals, but that numbers of symptoms correlated with plasma ammonium concentrations in EO patients only. Liver transplantation was reported for 90 NA and 25 EU patients. CONCLUSIONS: Combined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilizing differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies

HIV interactions with monocytes and dendritic cells: viral latency and reservoirs

HIV is a devastating human pathogen that causes serious immunological diseases in humans around the world. The virus is able to remain latent in an infected host for many years, allowing for the long-term survival of the virus and inevitably prolonging the infection process. The location and mechanisms of HIV latency are under investigation and remain important topics in the study of viral pathogenesis. Given that HIV is a blood-borne pathogen, a number of cell types have been proposed to be the sites of latency, including resting memory CD4+ T cells, peripheral blood monocytes, dendritic cells and macrophages in the lymph nodes, and haematopoietic stem cells in the bone marrow. This review updates the latest advances in the study of HIV interactions with monocytes and dendritic cells, and highlights the potential role of these cells as viral reservoirs and the effects of the HIV-host-cell interactions on viral pathogenesis

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion