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We describe detection of the previously rarely reported gram-positive bacterium Auritidibacter ignavus in 3 cases of chronic ear infections in Germany. In all 3 cases, the patients had refractory otorrhea. Although their additional symptoms varied, all patients had an ear canal stenosis and A. ignavus detected in microbiologic swab specimens. A correct identification of A. ignavus in the clinical microbiology laboratory is hampered by the inability to identify it by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Also, the bacterium might easily be overlooked because of its morphologic similarity to bacterial species of the resident skin flora. We conclude that a high index of suspicion is warranted to identify A. ignavus and that it should be particularly considered in patients with chronic external otitis who do not respond clinically to quinolone ear drop therapy.
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Micrococcaceae , Otite Externa , Humanos , Bactérias , Otite Externa/diagnóstico , Otite Externa/tratamento farmacológico , Otite Externa/microbiologia , Meato Acústico ExternoRESUMO
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a Hodgkin lymphoma expressing functional B-cell receptors (BCR). Recently, we described a dual stimulation model of IgD+ lymphocyte-predominant cells by Moraxella catarrhalis antigen RpoC and its superantigen MID/hag, associated with extralong CDR3 and HLA-DRB1*04 or HLADRB1* 07 haplotype. The aim of the present study was to extend the antigen screening to further bacteria and viruses. The fragment antibody-binding (Fab) regions of seven new and 15 previously reported cases were analyzed. The reactivity of non-Moraxella spp.-reactive Fab regions against lysates of Rothia mucilaginosa was observed in 5/22 (22.7%) cases. Galactofuranosyl transferase (Gltf) and 2,3-butanediol dehydrogenase (Bdh) of R. mucilaginosa were identified by comparative silver- and immuno-staining in two-dimensional gels, with subsequent mass spectrometry and validation by western blots and enzyme-linked immunosorbent assay. Both R. mucilaginosa Gltf and Bdh induced BCR pathway activation and proliferation in vitro. Apoptosis was induced by recombinant Gltf/ETA'-immunotoxin conjugates in DEV cells expressing recombinant R. mucilaginosa-reactive BCR. Reactivity against M. catarrhalis RpoC was confirmed in 3/7 newly expressed BCR (total 10/22 reactive to Moraxella spp.), resulting in 15/22 (68.2%) cases with BCR reactivity against defined bacterial antigens. These findings strengthen the hypothesis of bacterial trigger contributing to subsets of NLPHL.
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Doença de Hodgkin , Micrococcaceae , Humanos , Doença de Hodgkin/patologia , Receptores de Antígenos de Linfócitos B , Linfócitos/patologiaRESUMO
Invasive infections caused by carbapenemase-producing bacteria are associated with excess mortality. We applied a rapid diagnostic test (RDT) on clinical samples with an elevated likelihood of carbapenemase-producing bacteria and documented its impact on antibiotic treatment decisions. Among 38 patients, twelve tested positive for infections caused by carbapenemase-producing bacteria (31.6%), mainly in blood cultures. KPC (n = 10) was more frequent than OXA-48 (n = 2). RDT-based carbapenemase detection led to a treatment modification to ceftazidime/avibactam-containing regimens in all patients before detailed antibiotic testing results became available. Eleven patients (92%) survived the acute infection, whereas one patient with a ceftazidime/avibactam- and colistin-resistant OXA-48-positive isolate died.
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Hemocultura/métodos , Testes Diagnósticos de Rotina/métodos , Infecções por Enterobacteriaceae/diagnóstico , Enterobacteriaceae/isolamento & purificação , Testes Imediatos , Idoso , Proteínas de Bactérias , Enterobacteriaceae/enzimologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , beta-LactamasesRESUMO
The development of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is often associated with neoplasia or infectious diseases as antibodies against neurons or synaptic proteins surface. A 30-year-old male patient was admitted to our department because of neurocognitive symptoms, particularly memory difficulties which had appeared a year prior and since then had been increasing. He had a medical history of smoking and hypertension. On examination, there were no focal neurological deficits. However, neuropsychological tests confirmed a lack of concentration and short-term memory impairment. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) remained unremarkable. Cerebrospinal fluid (CSF) analysis revealed a low lymphocytic pleocytosis without oligoclonal bands. Serum testing for human immunodeficiency virus (HIV) was positive with 420,000 HIV-1-RNA copies/ml. On a more detailed physical examination, a large number of purple patches were found on the entire body, which a biopsy confirmed to be Kaposi sarcoma (KS). A positive serum and CSF NMDA receptor antibody titer (serum 1:280; CSF 1:8) confirmed the diagnosis of an AIDS-associated anti-NMDA receptor encephalitis; therefore, we treated him with antiretroviral and immunosuppressive therapy. After 12 months, the KS lesions faded and the cognitive deficits improved slightly. Our case highlights that a detailed clinical examination and searching for neoplasia and/or an infection are helpful, though often neglected, tools for detecting an anti-NMDA receptor encephalitis.
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Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Infecções por HIV/complicações , Encefalite Límbica/imunologia , Sarcoma de Kaposi/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , HIV-1 , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Encefalite Límbica/tratamento farmacológico , Masculino , Sarcoma de Kaposi/tratamento farmacológicoRESUMO
BACKGROUND: Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. METHODS: Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. RESULTS: The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. CONCLUSIONS: ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.
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Antibacterianos/análise , Monitoramento de Medicamentos/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Terapia de Substituição Renal/estatística & dados numéricos , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Ceftazidima/administração & dosagem , Ceftazidima/análise , Ceftazidima/sangue , Monitoramento de Medicamentos/instrumentação , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Alemanha , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Linezolida/administração & dosagem , Linezolida/análise , Linezolida/sangue , Masculino , Meropeném/administração & dosagem , Meropeném/análise , Meropeném/sangue , Pessoa de Meia-Idade , Combinação Piperacilina e Tazobactam/administração & dosagem , Combinação Piperacilina e Tazobactam/análise , Combinação Piperacilina e Tazobactam/sangue , Estudos Prospectivos , Terapia de Substituição Renal/métodosRESUMO
Background: Diagnostic pathways for patients presenting with cognitive complaints may vary across geographies. Objective: To describe diagnostic pathways of patients presenting with cognitive complaints across 6 countries. Methods: This real-world, cross-sectional study analyzed chart-extracted data from healthcare providers (HCPs) for 6,744 patients across China, France, Germany, Spain, UK, and the US. Results: Most common symptoms at presentation were cognitive (memory/amnestic; 89.86%), followed by physical/behavioral (87.13%). Clinical/cognitive tests were used inâ>â95%, with Mini-Mental State Examination being the most common cognitive test (79.0%). Blood tests for APOE É4/other mutations, or to rule out treatable causes, were used in half of the patients. Clinical and cognitive tests were used at higher frequency at earlier visits, and amyloid PET/CSF biomarker testing at higher frequency at later visits. The latter were ordered at low rates even by specialists (across countries, 5.7% to 28.7% for amyloid PET and 5.0% to 27.3% for CSF testing). Approximately half the patients received a diagnosis (52.1% of which were Alzheimer's disease [AD]). Factors that influenced risk of not receiving a diagnosis were HCP type (higher for primary care physicians versus specialists) and region (highest in China and Germany). Conclusion: These data highlight variability in AD diagnostic pathways across countries and provider types. About 45% of patients are referred/told to 'watch and wait'. Improvements can be made in the use of amyloid PET and CSF testing. Efforts should focus on further defining biomarkers for those at risk for AD, and on dismantling barriers such low testing capacity and reimbursement challenges.
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We analyzed consecutive clinical cases of infections due to carbapenemase-producing gram-negative bacteria detected in war-wounded patients from Ukraine who were treated at one university medical center in southwest Germany between June and December 2022. The isolates of multiresistant gram-negative bacteria were subjected to a thorough microbiological characterization and whole genome sequencing (WGS). We identified five war-wounded Ukrainian patients who developed infections with New Delhi metallo-ß-lactamase 1-positive Klebsiella pneumoniae. Two isolates also carried OXA-48 carbapenemases. The bacteria were resistant to novel antibiotics, such as ceftazidime/avibactam and cefiderocol. The used treatment strategies included combinations of ceftazidime/avibactam + aztreonam, colistin, or tigecycline. WGS suggested transmission during primary care in Ukraine. We conclude that there is an urgent need for thorough surveillance of multiresistant pathogens in patients from war zones.
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Ceftazidima , Refugiados , Humanos , Ceftazidima/uso terapêutico , Ucrânia/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , beta-Lactamases/genética , Proteínas de Bactérias/genética , Compostos Azabicíclicos/uso terapêutico , Combinação de Medicamentos , Bactérias Gram-Negativas/genética , Testes de Sensibilidade Microbiana , Klebsiella pneumoniae/genéticaRESUMO
An approach is developped to gain control over the polarity of neuronal networks at the cellular level by physically constraining cell development by the use of micropatterns. It is demonstrated that the position and path of individual axons, the cell extension that propagates the neuron output signal, can be chosen with a success rate higher than 85%. This allows the design of small living computational blocks above silicon nanowires.
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Axônios/metabolismo , Dendritos/metabolismo , Nanofios/química , Neurônios/metabolismo , Silício/química , Animais , Axônios/ultraestrutura , Células Cultivadas , Dendritos/ultraestrutura , Camundongos , Microscopia Eletrônica de Varredura , Nanotecnologia/métodos , Neurônios/ultraestruturaRESUMO
The immunological response against Clostridioides difficile (C. difficile) is crucial for an improved understanding of disease mechanisms and the development of novel therapeutic strategies. From April 2014 to February 2015, adult patients with C. difficile infection (CDI) were recruited, and the clinical course and treatment response were carefully monitored. On day 1, 3, and 6 after diagnosis, patient plasma samples were screened for anti-GDH (glutamate dehydrogenase), anti-TcdA, anti-TcdB, and anti-CWP84 (cell-wall protein 84) antibodies by ELISA. Additionally, neutralization assays of toxins from conditioned media of clinical isolates (RT010, RT014, and RT027) were performed. Most patients with CDI (n = 46) had antibodies against GDH (85%) and CWP84 (61%), but only few had antibodies against TcdA (11%) and TcdB (28%). We found patients with neutralizing antibodies against C. difficile toxins (conditioned media) produced by RT027 (26%). A subgroup of these samples could neutralize both toxins from RT027 and RT014 [11%, (5/46)]; however, no single sample neutralized only RT014. Overall, neutralizing antibody titers were low (≤1:16). In a one week follow-up of acute infection, we never observed an early booster effect with seroconversion or antibody increases, irrespective of disease severity. No correlation was found between the presence of antigen-specific (ELISA) or neutralizing antibodies and the clinical course of disease. Anti-TcdB but not anti-TcdA antibodies correlated with the occurrence of neutralizing antibodies. In conclusion, natural antibody titers against C. difficile toxins were absent or low and were not associated with disease severity. The correlation between the anti-TcdB with toxin neutralization confirms the importance of TcdB for virulence of CDI. Alternative sensitization strategies, e.g., through vaccine development, are required to overcome the regular low-titer antibody production following natural intestinal C. difficile exposure.
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Burkitt lymphoma (BL) represents the most aggressive B-cell-lymphoma. Beside the hallmark of IG-MYC-translocation, surface B-cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra-nodal sites suggest antigenic triggers. To explore this hypothesis, BCRs of BL cell lines and cases were screened for reactivities against a panel of bacterial lysates, lysates of Plasmodium falciparum, a custom-made virome array and against self-antigens, including post-translationally modified antigens. An atypically modified, SUMOylated isoform of Bystin, that is, SUMO1-BYSL was identified as the antigen of the BCR of cell line CA46. SUMO1-BYSL was exclusively expressed in CA46 cells with K139 as site of the SUMOylation. Secondly, an atypically acetylated isoform of HSP40 was identified as the antigen of the BCR of cell line BL41. K104 and K179 were the sites of immunogenic acetylation, and the acetylated HSP40 isoform was solely present in BL41 cells. Functionally, addition of SUMO1-BYSL and acetylated HSP40 induced BCR pathway activation in CA46 and BL41 cells, respectively. Accordingly, SUMO1-BYSL-ETA' immunotoxin, produced by a two-step intein-based conjugation, led to the specific killing of CA46 cells. Autoantibodies directed against SUMO1-BYSL were found in 3 of 14 (21.4%), and autoantibodies against acetylated HSP40 in 1/14(7.1%) patients with sporadic Burkitt-lymphoma. No reactivities against antigens of the infectious agent spectrum could be observed. These results indicate a pathogenic role of autoreactivity evoked by immunogenic post-translational modifications in a subgroup of sporadic BL including two EBV-negative BL cell lines.
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The SARS-CoV-2 pandemic has highlighted the need for improved technologies to help control the spread of contagious pathogens. While rapid point-of-need testing plays a key role in strategies to rapidly identify and isolate infectious patients, current test approaches have significant shortcomings related to assay limitations and sample type. Direct quantification of viral shedding in exhaled particles may offer a better rapid testing approach, since SARS-CoV-2 is believed to spread mainly by aerosols. It assesses contagiousness directly, the sample is easy and comfortable to obtain, sampling can be standardized, and the limited sample volume lends itself to a fast and sensitive analysis. In view of these benefits, we developed and tested an approach where exhaled particles are efficiently sampled using inertial impaction in a micromachined silicon chip, followed by an RT-qPCR molecular assay to detect SARS-CoV-2 shedding. Our portable, silicon impactor allowed for the efficient capture (>85%) of respiratory particles down to 300 nm without the need for additional equipment. We demonstrate using both conventional off-chip and in-situ PCR directly on the silicon chip that sampling subjects' breath in less than a minute yields sufficient viral RNA to detect infections as early as standard sampling methods. A longitudinal study revealed clear differences in the temporal dynamics of viral load for nasopharyngeal swab, saliva, breath, and antigen tests. Overall, after an infection, the breath-based test remains positive during the first week but is the first to consistently report a negative result, putatively signalling the end of contagiousness and further emphasizing the potential of this tool to help manage the spread of airborne respiratory infections.
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Técnicas Biossensoriais , COVID-19 , COVID-19/diagnóstico , Humanos , Estudos Longitudinais , RNA Viral/análise , Aerossóis e Gotículas Respiratórios , SARS-CoV-2 , SilícioRESUMO
CONTEXT: Pro-opiomelanocortin (POMC) and the melanocortin-4 receptor (MC4R) play a pivotal role in the leptin-melanocortin pathway. Mutations in these genes lead to monogenic types of obesity due to severe hyperphagia. In addition to dietary-induced obesity, a cardiac phenotype without hypertrophy has been identified in MC4R knockout mice. OBJECTIVE: We aimed to characterize cardiac morphology and function as well as tissue Na+ content in humans with mutations in POMC and MC4R genes. METHODS: A cohort of 42 patients (5 patients with bi-allelic POMC mutations, 6 heterozygous MC4R mutation carriers, 19 obese controls without known monogenic cause, and 12 normal weight controls) underwent cardiac magnetic resonance (CMR) imaging and 23Na-MRI. RESULTS: Monogenic obese patients with POMC or MC4R mutation respectively had a significantly lower left ventricular mass/body surface area (BSA) than nonmonogenic obese patients. Left ventricular end-diastolic volume/BSA was significantly lower in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. Subcutaneous fat and skin Na+ content was significantly higher in POMC- and MC4R-deficient patients than in nonmonogenic obese patients. In these compartments, the water content was significantly higher in patients with POMC and MC4R mutation than in control groups. CONCLUSION: Patients with POMC or MC4R mutations carriers had a lack of transition to hypertrophy, significantly lower cardiac muscle mass/BSA, and stored more Na+ within the subcutaneous fat tissue than nonmonogenic obese patients. The results point towards the role of the melanocortin pathway for cardiac function and tissue Na+ storage and the importance of including cardiologic assessments into the diagnostic work-up of these patients.
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Hipertrofia Ventricular Esquerda/etiologia , Mutação , Pró-Opiomelanocortina/genética , Receptor Tipo 4 de Melanocortina/genética , Sódio/metabolismo , Função Ventricular Esquerda/fisiologia , Adolescente , Água Corporal/metabolismo , Feminino , Humanos , Hipertrofia Ventricular Esquerda/genética , Imageamento por Ressonância Magnética , Masculino , Obesidade/complicações , Fenótipo , Pró-Opiomelanocortina/fisiologia , Receptor Tipo 4 de Melanocortina/fisiologiaRESUMO
The natural history of paroxysmal nocturnal hemoglobinuria (PNH) clinical subcategories (classic PNH and aplastic anemia [AA]/PNH syndrome) is still unknown. We retrospectively studied 460 PNH patients diagnosed in 58 French hematologic centers from 1950 to 2005. The median (SE) follow-up time was 6.8 (0.5) years. The median survival time (SE) was 22 (2.5) years. We identified 113 patients with classic PNH, 224 patients with AA-PNH syndrome, and 93 (22%) intermediate patients who did not fit within these 2 categories. At presentation, classic PNH patients were older, with more frequent abdominal pain and displayed higher levels of GPI-AP-deficient granulocytes. A time-dependent improved survival was observed. In classic PNH, diagnoses before 1986 (hazard ratio [HR]: 3.6; P = .01) and increasing age (P < .001) were associated with worse survival prognoses, whereas use of androgens within the first year after diagnosis was protective (HR, 0.17; P = .01). Transfusions before 1996 (HR, 2.7; P = .007) led to lower survival rates in patients with AA-PNH syndrome, whereas immunosuppressive treatment was associated with better outcomes (HR, 0.33; P = .03). Evolution to thrombosis affected survival in both subcategories (classic PNH: HR, 7.8 [P < .001]; AA-PNH syndrome: HR, 33.0 [P < .001]). Evolution to bicytopenia or pancytopenia for classic PNH (HR, 7.3, P < .001) and malignancies for AA-PNH syndrome (HR, 48.8; P < .001) were associated with worse outcomes. Although clinical presentation and prognosis factors are different, classic PNH and AA-PNH syndrome present roughly similar outcomes, affected mainly by complications.
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Hemoglobinúria Paroxística/classificação , Hemoglobinúria Paroxística/diagnóstico , Adulto , Feminino , Hematologia/métodos , Hemoglobinúria Paroxística/complicações , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Risco , Trombose/genética , Fatores de Tempo , Resultado do TratamentoRESUMO
Corynebacterium kroppenstedtii is an emerging cause of granulomatous mastitis and recurrent breast abscesses in women, but data on its clinical relevance in nongynecological disease conditions are limited. Here, we report the first case of a late-onset endocarditis of a native aortic valve in a 73-year-old male patient who presented with symptomatic aortic insufficiency. Echocardiography and cardiac computed tomography revealed the perforation of the noncoronary cusp and a large perivalvular abscess cavity. Hence, the surgical replacement of the aortic valve and aortic root were performed. Intraoperatively obtained tissue specimens grew C. kroppenstedtii and the patient made a full recovery after a 6-week course of antibiotic treatment. We briefly review the literature pertaining to antimicrobial susceptibility patterns of C. kroppenstedtii and available treatment recommendations. Our report calls for further studies to assess the role of this bacterium as a causative agent of infections other than granulomatous mastitis.
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Valvopatia Aórtica/microbiologia , Infecções por Corynebacterium/complicações , Corynebacterium , Idoso , Antibacterianos/uso terapêutico , Valvopatia Aórtica/diagnóstico , Valvopatia Aórtica/tratamento farmacológico , Infecções por Corynebacterium/diagnóstico , Infecções por Corynebacterium/microbiologia , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Humanos , MasculinoRESUMO
Patients with pre-existing comorbidities and immunosuppression are at greater risk for SARS-CoV-2 infection and severe manifestations of COVID-19. This also includes cancer patients, who are shown to have a poor prognosis after infection. Here, we describe the case of a 72-year old male patient with B-cell depletion after maintenance treatment with rituximab for non-Hodgkin-lymphoma who had a prolonged COVID-19 course and initial false negative test results. Our case highlights the diagnostic pitfalls in diagnosing COVID-19 in B-cell depleted patients and discuss the role of B-cell depletion in the course and treatment of COVID-19. Furthermore, we investigated peripheral blood monocytes and SARS-CoV-2 specific T cells in our patient. In conclusion, our case report can help physicians to avoid diagnostic pitfalls for COVID-19 in hemato-oncological patients under chemoimmunotherapy and tries to explain the role of B-cell depletion and SARS-CoV-2 specific T cells in this context.
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OBJECTIVE: We aimed to investigate the combined effects of arterial hypertension, bicuspid aortic valve disease (BAVD) and age on the distensibility of the ascending and descending aortas in patients with aortic coarctation. DESIGN: Cross-sectional study. SETTING: The study was conducted at two university medical centres, located in Berlin and London. PARTICIPANTS: A total of 121 patients with aortic coarctation (ages 1-71 years) underwent cardiac MRI, echocardiography and blood pressure measurements. OUTCOME MEASURES: Cross-sectional diameters of the ascending and descending aortas were assessed to compute aortic area distensibility. Findings were compared with age-specific reference values. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology statement and reporting guidelines. RESULTS: Impaired distensibility (below fifth percentile) was seen in 37% of all patients with coarctation in the ascending aorta and in 43% in the descending aorta. BAVD (43%) and arterial hypertension (72%) were present across all ages. In patients >10 years distensibility impairment of the ascending aorta was predominantly associated with BAVD (OR 3.1, 95% CI 1.33 to 7.22, p=0.009). Distensibility impairment of the descending aorta was predominantly associated with arterial hypertension (OR 2.8, 95% CI 1.08 to 7.2, p=0.033) and was most pronounced in patients with uncontrolled hypertension despite antihypertensive treatment. CONCLUSION: From early adolescence on, both arterial hypertension and BAVD have a major impact on aortic distensibility. Their specific effects differ in strength and localisation (descending vs ascending aorta). Moreover, adequate blood pressure control is associated with improved distensibility. These findings could contribute to the understanding of cardiovascular complications and the management of patients with aortic coarctation.
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Envelhecimento/patologia , Aorta/patologia , Coartação Aórtica/patologia , Doença da Válvula Aórtica Bicúspide/patologia , Hipertensão/patologia , Adolescente , Adulto , Coartação Aórtica/epidemiologia , Doença da Válvula Aórtica Bicúspide/epidemiologia , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Adulto JovemRESUMO
Background: Liberal PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to contain the coronavirus disease 2019 (COVID-19) pandemic. Combined multi-sample testing in pools instead of single tests might enhance laboratory capacity and reduce costs, especially in low- and middle-income countries. Objective: The purpose of our study was to assess the value of a simple questionnaire to guide and further improve pooling strategies for SARS-CoV-2 laboratory testing. Methods: Pharyngeal swabs for SARS-CoV-2 testing were obtained from healthcare and police staff, hospital inpatients, and nursing home residents in the southwestern part of Germany. We designed a simple questionnaire, which included questions pertaining to a suggestive clinical symptomatology, recent travel history, and contact with confirmed cases to stratify an individual's pre-test probability of having contracted COVID-19. The questionnaire was adapted repeatedly in face of the unfolding pandemic in response to the evolving epidemiology and observed clinical symptomatology. Based on the response patterns, samples were either tested individually or in multi-sample pools. We compared the pool positivity rate and the number of total PCR tests required to obtain individual results between this questionnaire-based pooling strategy and randomly assembled pools. Findings: Between March 11 and July 5, 2020, we processed 25,978 samples using random pooling (n = 6,012; 23.1%) or questionnaire-based pooling (n = 19,966; 76.9%). The overall prevalence of SARS-CoV-2 was 0.9% (n = 238). Pool positivity (14.6% vs. 1.2%) and individual SARS-CoV-2 prevalence (3.4% vs. 0.1%) were higher in the random pooling group than in the questionnaire group. The average number of PCR tests needed to obtain the individual result for one participant was 0.27 tests in the random pooling group, as compared to 0.09 in the questionnaire-based pooling group, leading to a laboratory capacity increase of 73% and 91%, respectively, as compared to single PCR testing. Conclusions: Strategies that combine pool testing with a questionnaire-based risk stratification can increase laboratory testing capacities for COVID-19 and might be important tools, particularly in resource-constrained settings.
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Teste para COVID-19/métodos , Teste para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Serviços de Laboratório Clínico/estatística & dados numéricos , Serviços de Laboratório Clínico/provisão & distribuição , Alemanha/epidemiologia , Humanos , Faringe/virologia , Prevalência , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de RiscoRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Early-onset obesity is known to culminate in type 2 diabetes, arterial hypertension and subsequent cardiovascular disease. The role of sodium (Na+) homeostasis in this process is incompletely understood, yet correlations between Na+ accumulation and hypertension have been observed in adults. We aimed to investigate these associations in adolescents. A cohort of 32 adolescents (13-17 years), comprising 20 obese patients, of whom 11 were hypertensive, as well as 12 age-matched controls, underwent 23Na-MRI of the left lower leg with a standard clinical 3T scanner. Median triceps surae muscle Na+ content in hypertensive obese (11.95 mmol/L [interquartile range 11.62-13.66]) was significantly lower than in normotensive obese (13.63 mmol/L [12.97-17.64]; p = 0.043) or controls (15.37 mmol/L [14.12-16.08]; p = 0.012). No significant differences were found between normotensive obese and controls. Skin Na+ content in hypertensive obese (13.33 mmol/L [11.53-14.22] did not differ to normotensive obese (14.12 mmol/L [13.15-15.83]) or controls (11.48 mmol/L [10.48-12.80]), whereas normotensive obese had higher values compared to controls (p = 0.004). Arterial hypertension in obese adolescents is associated with low muscle Na+ content. These findings suggest an early dysregulation of Na+ homeostasis in cardiometabolic disease. Further research is needed to determine whether this association is causal and how it evolves in the transition to adulthood.