[Kidney disease in antiphospholipid antibody syndrome]. / Manifestations rénales du syndrome des anticorps antiphospholipides.

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events. Renal complications occur in 3 % of patients. Renal artery stenosis is the most common, and APS-related nephropathy is the predominant microvascular complication. APS nephropathy has heterogeneous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension and multi-organ failure caused by catastrophic antiphospholipid antibody syndrome. Anticoagulation and thromboprophylaxis are key to management. Immunosuppression has been used with some success but lacks randomized controlled trial validation for their use.

Le syndrome des anticorps antiphospholipides (SAPL) est une maladie auto-immune rare caractérisée par des événements thromboemboliques artériels et veineux récurrents. Les complications rénales surviennent chez 3 % des patients. La sténose de l'artère rénale est la plus courante et la néphropathie liée au SAPL représente la complication microvasculaire principale. La maladie rénale liée au SAPL se traduit par des manifestations hétérogènes allant de l'hématurie et de la protéinurie non néphrotique à l'hypertension jusqu'à la défaillance multi-organique causée par le syndrome catastrophique des anticorps antiphospholipides (SCAPL). L'anticoagulation et la thromboprophylaxie sont clés dans la prise en charge. L'immunosuppression a été utilisée avec un certain succès, mais manque de validation par des essais contrôlés randomisés pour leur utilisation.

Therapeutic considerations for APOE and TOMM40 in Alzheimers disease: A tribute to Allen Roses MD.

Introduction: Four years ago this Autumn, pioneering neurologist Prof. Allen. D. Roses passed away. Hence, we have taken time to reflect on his work and legacy in Alzheimer's disease (AD) research. Prof. Roses rejected the widely accepted amyloid hypothesis, which identifies amyloid beta (Aß) protein accumulation within the brain as the cause of AD. Instead, he proposed that the epsilon type 4 allele of apolipoprotein (APOE- Ɛ4) and translocase of outer mitochondrial membrane 40 homolog (TOMM40) were preeminent factors in the pathogenesis and progression of AD, particularly in late-onset AD (LOAD). This rejection of the amyloid hypothesis has generated new investigations into APOE and TOMM40 as risk factors for AD. Areas covered: We discuss the contributions of Prof. Roses to AD research, describe how APOE-Ɛ4 and TOMM40 have been posited to trigger neuropathological changes leading to AD, and explore paths to future clinical applications built on the foundations of his research. Expert opinion: The unconventional methodology of targeting APOE and TOMM40 offers great potential for the development of effective preventive and disease-modifying AD interventions. Future preclinical and clinical investigations will greatly benefit from the groundbreaking scientific discoveries of Prof. Roses.

Dementia with Lewy bodies: emerging drug targets and therapeutics.

Introduction: Dementia with Lewy bodies (DLB) is characterized by the toxic accumulation of α-synuclein protein inside neural cells; this results in neurodegeneration which is clinically accompanied by behavioral and psychological changes. DLB shares features with Parkinson's disease (PD) and Parkinson's disease dementia (PDD), but also overlaps neurochemically and pathologically with Alzheimer's disease. Symptomatic treatments for LBD differ in their effectiveness while disease-modifying and curative approaches are much needed.Areas covered: We explore emerging therapeutics for DLB through the lens of repurposing approved drugs and survey their potential for disease modifying actions in DLB. Given the complexity of DLB with multiple pathologies, potential therapeutic targets that could affect Lewy body pathology, or metabolism or neurotransmitters or immunomodulation were surveyed. We queried PubMed and ClinicalTrials.gov searches 2017-2020.Expert opinion: DLB is not simply aredux ofAD or PD; hence, treatments should not be exclusively duplicative ofAD or PD directed treatments. This opens amyriad of possibilities for therapeutic approaches that are disease specific or repurposed.

What Promises the CJD Diagnosis in a Case of Rapidly Progressive Dementia?

BACKGROUND: Developing methods for accurately diagnosing prion diseases has been a challenge in the search for successful diagnosis and treatment of rapidly progressive dementia. prion diseases are rare. However, they should be considered in the differential diagnosis. Despite their rarity, several other conditions are often misdiagnosed as prion diseases. Most Alzheimer's (AD) and Lewy Body Disease (LBD) patients also meet Creutzfeldt-Jakob Disease (CJD) criteria. The similarities in symptomology and pathology between these two patient groups complicates diagnosis and can compromise patient care. Prevalent methods for the diagnosis of CJD lack the heightened sensitivity to conclusively detect CJD. Of all currently available methods, real-time quaking induced conversion (RT-QuIC) analysis provides the highest sensitivity necessary to allow for an accurate diagnosis and yields early, quantitative results. CLINICAL CASE: A 75-year-old woman with rapidly progressing dementia, for which CJD could not be ruled out, appeared for care at a neurological center. Laboratory test results, Magnetic Resonance Imaging (MRI), Cerebrospinal Fluid (CSF) studies, Positron Emission Tomography (PET), and an Electroencephalogram (EEG) proved inadequate to confirm CJD. In addition to AD, LBD, or CJD, other potential, yet improbable, pathologies could have caused the patient's symptoms. The patient's diagnosis ultimately was limited to either LBD or prion disease. Spongiform encephalogy was confirmed by a brain biopsy, and further testing confirmed sporadic CJD. CONCLUSION: RT-QuIC offers higher sensitivity than currently prevalent diagnostic methods and appears most promising for CJD diagnosis.

A community outbreak of Legionnaires' disease in Geneva, Switzerland, June to September 2017.

PURPOSE: Eight confirmed cases of Legionnaires’ disease were identified at the Geneva University Hospitals between 28 July 2017 and 02 August 2017, leading to a detailed outbreak investigation. METHODS: Legionnaires’ disease cases were defined according to Swiss and European (ELDSNet) consensus guidelines. An outbreak investigation task force was put in place. Patients were interviewed, when feasible, with a standard questionnaire. A Legionella pneumophila urinary antigen test was performed in all cases. Lower respiratory tract (LRT) specimens were collected for culture, polymerase chain-reaction (PCR) assay, monoclonal antibody subtyping and sequenced-based typing (SBT). Multiple environmental samples were collected. Case geographical mapping was performed and local meteorological data were obtained. RESULTS: Thirty-four confirmed cases of Legionnaires’ disease were identified between 20 June 2017 and 16 September 2017, including 28 patients living in the Canton of Geneva and 6 cases in neighbouring cantons and France. The case fatality rate was 8.8%. The urinary antigen test was positive in 32/34 (94.1%) cases. Among the 17/34 (50%) cases with available LRT specimens, 8 (47.1%) were culture/PCR positive, 5 (29.4%) were PCR positive only, and 4 (23.5%) were culture/PCR negative. Monoclonal antibody subtyping and SBT on 12 samples allowed subtype identification of 8 samples, with a predominance of L. pneumophila serogroup-1 subtype-France/Allentown ST23 among clinical isolates. A specific city area was identified as a possible outbreak epicentre in 25/34 (73.5%) cases, although molecular analysis of clinical and environmental specimens revealed heterogeneous subtypes of L. pneumophila. CONCLUSIONS: In this largest documented outbreak of Legionnaires’ disease in Switzerland, we report prompt outbreak identification, leading to timely initiation of a detailed, well-orchestrated clinical and epidemiological investigation.