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2.
Environ Sci Technol ; 58(13): 5716-5726, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38503264

RESUMEN

Mitochondria play a key role in the energy production of cells, but their function can be disturbed by environmental toxicants. We developed a cell-based mitochondrial toxicity assay for environmental chemicals and their mixtures extracted from water samples. The reporter gene cell line AREc32, which is frequently used to quantify the cytotoxicity and oxidative stress response of water samples, was multiplexed with an endpoint of mitochondrial toxicity. The disruption of the mitochondrial membrane potential (MMP) was quantified by high-content imaging and compared to measured cytotoxicity, predicted baseline toxicity, and activation of the oxidative stress response. Mitochondrial complex I inhibitors showed highly specific effects on the MMP, with minor effects on cell viability. Uncouplers showed a wide distribution of specificity on the MMP, often accompanied by specific cytotoxicity (enhanced over baseline toxicity). Mitochondrial toxicity and the oxidative stress response were not directly associated. The multiplexed assay was applied to water samples ranging from wastewater treatment plant (WWTP) influent and effluent and surface water to drinking and bottled water from various European countries. Specific effects on MMP were observed for the WWTP influent and effluent. This new MitoOxTox assay is an important complement for existing in vitro test batteries for water quality testing and has potential for applications in human biomonitoring.


Asunto(s)
Contaminantes Químicos del Agua , Calidad del Agua , Humanos , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Mitocondrias/química , Estrés Oxidativo , Bioensayo/métodos
3.
Anal Bioanal Chem ; 416(12): 2983-2993, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38556595

RESUMEN

Liquid chromatography (LC) or gas chromatography (GC) coupled to high-resolution mass spectrometry (HRMS) is a versatile analytical method for the analysis of thousands of chemical pollutants that can be found in environmental and biological samples. While the tools for handling such complex datasets have improved, there are still no fully automated workflows for targeted screening analysis. Here we present an R-based workflow that is able to cope with challenging data like noisy ion chromatograms, retention time shifts, and multiple peak patterns. The workflow can be applied to batches of HRMS data recorded after GC with electron ionization (GC-EI) and LC coupled to electrospray ionization in both negative and positive mode (LC-ESIneg/LC-ESIpos) to perform peak annotation and quantitation fully unsupervised. We used Orbitrap HRMS data of surface water extracts to compare the Automated Target Screening (ATS) workflow with data evaluations performed with the vendor software TraceFinder and the established semi-automated analysis workflow in the MZmine software. The ATS approach increased the overall evaluation performance of the peak annotation compared to the established MZmine module without the need for any post-hoc corrections. The overall accuracy increased from 0.80 to 0.86 (LC-ESIpos), from 0.77 to 0.83 (LC-ESIneg), and from 0.67 to 0.76 (GC-EI). The mean average percentage errors for quantification of ATS were around 30% compared to the manual quantification with TraceFinder. The ATS workflow enables time-efficient analysis of GC- and LC-HRMS data and accelerates and improves the applicability of target screening in studies with a large number of analytes and sample sizes without the need for manual intervention.


Asunto(s)
Flujo de Trabajo , Espectrometría de Masas/métodos , Programas Informáticos , Automatización , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Contaminantes Químicos del Agua/análisis
4.
Artículo en Alemán | MEDLINE | ID: mdl-37985511

RESUMEN

BACKGROUND: The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients. AIMS, MATERIALS AND METHODS: The following review aims to show the importance of gastrointestinal dysfunction. Multimodal therapy for gastroparesis and paralytic ileus is discussed. CONCLUSION: Erythromycin and metoclopramide are options for gastroparesis, while neostigmine is commonly used for paralytic ileus.

5.
Environ Sci Technol ; 57(48): 19363-19373, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37987701

RESUMEN

Human biomonitoring studies are important for understanding adverse health outcomes caused by exposure to chemicals. Complex mixtures of chemicals detected in blood - the blood exposome - may serve as proxies for systemic exposure. Ideally, several analytical methods are combined with in vitro bioassays to capture chemical mixtures as diverse as possible. How many and which (bio)analyses can be performed is limited by the sample volume and compatibility of extraction and (bio)analytical methods. We compared the extraction efficacy of three extraction methods using pooled human plasma spiked with >400 organic chemicals. Passive equilibrium sampling (PES) with polydimethylsiloxane (PDMS) followed by solid phase extraction (PES + SPE), SPE alone (SPE), and solvent precipitation (SolvPrec) were compared for chemical recovery in LC-HRMS and GC-HRMS as well as effect recovery in four mammalian cell lines (AhR-CALUX, SH-SY5Y, AREc32, PPARγ-BLA). The mean chemical recoveries were 38% for PES + SPE, 27% for SPE, and 61% for SolvPrec. PES + SPE enhanced the mean chemical recovery compared to SPE, especially for neutral hydrophobic chemicals. PES + SPE and SolvPrec had effect recoveries of 100-200% in all four cell lines, outperforming SPE, which had 30-100% effect recovery. Although SolvPrec has the best chemical recoveries, it does not remove matrix like inorganics or lipids, which might pose problems for some (bio)analytical methods. PES + SPE is the most promising method for sample preparation in human biomonitoring as it combines good recoveries with cleanup, enrichment, and potential for high throughput.


Asunto(s)
Neuroblastoma , Animales , Humanos , Compuestos Orgánicos , Bioensayo/métodos , Extracción en Fase Sólida/métodos , Mamíferos
6.
Endoscopy ; 55(10): 940-944, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37160261

RESUMEN

BACKGROUND : Outbreaks of multidrug-resistant bacteria due to contaminated duodenoscopes and infection risks during the COVID-19 pandemic have driven the development of single-use endoscopes. The first single-use gastroscope is now available in Europe. Besides waste disposal and cost issues, the infection risk and performance remain unclear. We aimed to evaluate a single-use gastroscope in patients with signs of upper gastrointestinal bleeding. METHODS : 20 consecutive patients presenting with clinical signs of upper gastrointestinal bleeding between October and November 2022 were included in this case series. The primary aim was technical success, defined as access to the descending duodenum and adequate assessment of the upper gastrointestinal tract for the presence of a bleeding site. RESULTS : The primary aim was achieved in 19/20 patients (95 %). The bleeding site was identified in 18 patients. A therapeutic intervention was performed in six patients (two cap-mounted clips, one standard hemostatic clip, two variceal band ligations, one hemostatic powder, two adrenaline injections); technical and clinical success were achieved in all six patients. Two crossovers to a standard gastroscope occurred. CONCLUSIONS : Use of single-use gastroscopes may be feasible for patients presenting for urgent endoscopic evaluation and treatment of upper gastrointestinal bleeding.


Asunto(s)
COVID-19 , Hemostasis Endoscópica , Hemostáticos , Humanos , Gastroscopios , Estudios de Factibilidad , Pandemias , Resultado del Tratamiento , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Hemostasis Endoscópica/métodos
7.
Environ Int ; 171: 107680, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36502700

RESUMEN

Modern society continues to pollute the environment with larger quantities of chemicals that have also become more structurally and functionally diverse. Risk assessment of chemicals can hardly keep up with the sheer numbers that lead to complex mixtures of increasing chemical diversity including new chemicals, substitution products on top of still abundant legacy compounds. Fortunately, over the last years computational tools have helped us to identify and prioritize chemicals of concern. These include toxicokinetic models to predict exposure to chemicals as well as new approach methodologies such as in-vitro bioassays to address toxicodynamic effects. Combined, they allow for a prediction of mixtures and their respective effects and help overcome the lack of data we face for many chemicals. In this study we propose a high-throughput approach using experimental and predicted exposure, toxicokinetic and toxicodynamic data to simulate mixtures, to which a virtual population is exposed to and predict their mixture effects. The general workflow is adaptable for any type of toxicity, but we demonstrated its applicability with a case study on neurotoxicity. If no experimental data for neurotoxicity were available, we used baseline toxicity predictions as a surrogate. Baseline toxicity is the minimal toxicity any chemical has and might underestimate the true contribution to the mixture effect but many neurotoxicants are not by orders of magnitude more potent than baseline toxicity. Therefore, including baseline-toxic effects in mixture simulations yields a more realistic picture than excluding them in mixture simulations. This workflow did not only correctly identify and prioritize known chemicals of concern like benzothiazoles, organochlorine pesticides and plasticizers but we were also able to identify new potential neurotoxicants that we recommend to include in future biomonitoring studies and if found in humans, to also include in neurotoxicity screening.


Asunto(s)
Monitoreo Biológico , Hidrocarburos Clorados , Humanos , Toxicocinética , Medición de Riesgo , Mezclas Complejas
8.
Med Klin Intensivmed Notfmed ; 117(8): 658-666, 2022 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-36214834

RESUMEN

In critically ill patients an intra-abdominal hypertension (IAH) is a frequent phenomenon. An IAH is defined as an intra-abdominal pressure (IAP) persistently ≥ 12 mm Hg and an abdominal compartment syndrome is defined as an IAP with a persistent pressure ≥ 20 mm Hg in combination with newly occurring organ failure. The bladder pressure serves as a surrogate parameter for the IAP, which should be measured noninvasively in a standardized manner. An undetected and untreated IAH worsens the prognosis of critically ill patients.


Asunto(s)
Enfermedad Crítica , Hipertensión Intraabdominal , Humanos , Estudios Prospectivos , Hipertensión Intraabdominal/diagnóstico , Hipertensión Intraabdominal/terapia , Pronóstico
9.
Gut ; 71(12): 2388-2390, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36109151

RESUMEN

In this study, we aimed to develop an artificial intelligence clinical decision support solution to mitigate operator-dependent limitations during complex endoscopic procedures such as endoscopic submucosal dissection and peroral endoscopic myotomy, for example, bleeding and perforation. A DeepLabv3-based model was trained to delineate vessels, tissue structures and instruments on endoscopic still images from such procedures. The mean cross-validated Intersection over Union and Dice Score were 63% and 76%, respectively. Applied to standardised video clips from third-space endoscopic procedures, the algorithm showed a mean vessel detection rate of 85% with a false-positive rate of 0.75/min. These performance statistics suggest a potential clinical benefit for procedure safety, time and also training.


Asunto(s)
Aprendizaje Profundo , Resección Endoscópica de la Mucosa , Humanos , Inteligencia Artificial , Endoscopía Gastrointestinal
10.
Mod Pathol ; 35(8): 1013-1021, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35365771

RESUMEN

The rate of SARS-CoV-2 infections in vaccinees has become a relevant serious issue. This study aimed to determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types for deceased individuals with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Twenty-nine consecutively collected cases were analyzed and compared to 141 nonvaccinated control cases. Autopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within organ systems in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008) mainly with Ct-values of higher than 25 in non-respiratory samples. However, vaccinated cases also showed high viral loads, reaching Ct-values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors, such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. The virus dissemination observed in our case study may indicate that patients with an impaired immune system have a decreased ability to eliminate the virus. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies. Fatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions.


Asunto(s)
COVID-19 , Anciano , Autopsia , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2 , Carga Viral
11.
Minim Invasive Ther Allied Technol ; 31(5): 704-711, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34342252

RESUMEN

INTRODUCTION: Risk stratification in upper gastrointestinal bleeding (UGIB) currently relies on clinical parameters and risk scores. HemoPill® acute (Ovesco Endoscopy, Tuebingen, Germany) is a pill-shaped, orally administered sensor capsule for real-time blood detection. The aim of this study was to evaluate the system in clinical routine. MATERIAL AND METHODS: Sixty-one consecutive patients in whom the HemoPill® had been used at 12 international hospitals between July 2019 and March 2020 were retrospectively analysed. Indications for application were the clinical suspicion of UGIB, small bowel bleeding, of rebleeding after hemostasis. Primary endpoints were technical success and bleeding detection/exclusion. Secondary endpoints included adverse events and change of clinical course. RESULTS: The capsule was used in 45 (73%) patients with UGIB, in 12 (20%) patients with small bowel bleeding and in four (7%) patients for exclusion of rebleeding. Technical success was 98%. 35/60 (58%) cases were capsule-positive and among these, endoscopy showed bleeding in 20/35 (57%) cases. None of the 25 capsule-negative patients rebled. Emergency endoscopy could be avoided in 18/25 (72%) cases. Serious adverse events did not occur. CONCLUSION: HemoPill®-based blood detection is feasible and safe. Negative capsule results might 'downgrade' the need for urgent endoscopy.


Asunto(s)
Tracto Gastrointestinal Superior , Endoscopía Gastrointestinal , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Estudios Retrospectivos , Factores de Riesgo
13.
Anaesthesist ; 70(11): 977-990, 2021 11.
Artículo en Alemán | MEDLINE | ID: mdl-34709412

RESUMEN

Endoscopy is most frequently performed in intensive care units (ICU) for gastrointestinal bleeding; however, there are other indications for performing an endoscopy on the ICU. This article shows the indications for this, the background and the peri-interventional and postinterventional management. The endoscopic placement of a postpyloric feeding tube is a well-established procedure. For anastomotic leakage in the esophagus and rectum, the endoscopic vacuum therapy is the treatment of choice. Gastrointestinal motility disorders are a frequent phenomenon in critically ill patients and are associated with increased mortality. With a cecal diameter > 9-12 mm, endoscopic decompression can be performed; however, this is associated with an increased risk of perforation and should only be carried out after the failure of conservative treatment.


Asunto(s)
Descompresión Quirúrgica , Vértebras Lumbares , Cuidados Críticos , Enfermedad Crítica , Endoscopía , Humanos , Unidades de Cuidados Intensivos
14.
United European Gastroenterol J ; 9(9): 1081-1090, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34655180

RESUMEN

BACKGROUND: Corona virus disease 2019 (COVID-19) patients are at increased risk for thromboembolic events. It is unclear whether the risk for gastrointestinal (GI) bleeding is also increased. METHODS: We considered 4128 COVID-19 patients enrolled in the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. The association between occurrence of GI bleeding and comorbidities as well as medication were examined. In addition, 1216 patients from COKA registry were analyzed focusing on endoscopy diagnostic findings. RESULTS: A cumulative number of 97 patients (1.8%) with GI bleeding were identified in the LEOSS registry and COKA registry. Of 4128 patients from the LEOSS registry, 66 patients (1.6%) had a GI bleeding. The rate of GI bleeding in patients with intensive care unit (ICU) admission was 4.5%. The use of therapeutic dose of anticoagulants showed a significant association with the increased incidence of bleeding in the critical phase of disease. The Charlson comorbidity index and the COVID-19 severity index were significantly higher in the group of patients with GI bleeding than in the group of patients without GI bleeding (5.83 (SD = 2.93) vs. 3.66 (SD = 3.06), p < 0.01 and 3.26 (SD = 1.69) vs. 2.33 (SD = 1.53), p < 0.01, respectively). In the COKA registry 31 patients (2.5%) developed a GI bleeding. Of these, the source of bleeding was identified in upper GI tract in 21 patients (67.7%) with ulcer as the most frequent bleeding source (25.8%, n = 8) followed by gastroesophageal reflux (16.1%, n = 5). In three patients (9.7%) GI bleeding source was located in lower GI tract caused mainly by diverticular bleeding (6.5%, n = 2). In seven patients (22.6%) the bleeding localization remained unknown. CONCLUSION: Consistent with previous research, comorbidities and disease severity correlate with the incidence of GI bleeding. Also, therapeutic anticoagulation seems to be associated with a higher risk of GI bleeding. Overall, the risk of GI bleeding seems not to be increased in COVID-19 patients.


Asunto(s)
COVID-19/epidemiología , Endoscopía Gastrointestinal , Hemorragia Gastrointestinal/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Niño , Preescolar , Comorbilidad , Enfermedad Crítica , Enfermedades Diverticulares/diagnóstico , Europa (Continente)/epidemiología , Femenino , Reflujo Gastroesofágico/complicaciones , Hemorragia Gastrointestinal/etiología , Hospitalización , Humanos , Lactante , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Úlcera Péptica/diagnóstico , Sistema de Registros , Índice de Severidad de la Enfermedad , Adulto Joven
15.
Zentralbl Chir ; 146(6): 605-611, 2021 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-34706375

RESUMEN

BACKGROUND AND OBJECTIVES: It has been reported that the risk of deep vein thrombosis is greater in patients with COVID-19 infection. We have now investigated whether a standardised therapy can reduce the risk of DVT. MATERIALS AND METHODS: After establishing standard therapy with anticoagulation, steroids and convalescent plasma, we screened 20 patients with COVID-19 pneumonia for DVT by ultrasound examination. The comparison group contained 20 COVID patients with inconsistent therapy, who were examined for the presence of thrombosis during the first wave. RESULTS: In the current patient population with standard therapy, we could not detect any thrombosis, and in the prior patients group only 25% of patients developed DVT. Pulmonary embolism was found in one patient in the first cohort and two in the second. CONCLUSION: The risk of DVT could be reduced through anticoagulation, and administration of steroids and convalescent plasma. The specific significance of the individual components has not yet been clarified. Since bleeding is a rarely observed in SARS-CoV-2 infections, a generous indication for anticoagulation seems to be justified.


Asunto(s)
COVID-19 , Embolia Pulmonar , Trombosis de la Vena , Anticoagulantes/uso terapéutico , COVID-19/terapia , Cuidados Críticos , Humanos , Inmunización Pasiva , SARS-CoV-2 , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/tratamiento farmacológico , Sueroterapia para COVID-19
16.
Chem Res Toxicol ; 34(9): 2100-2109, 2021 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-34357765

RESUMEN

All chemicals can interfere with cellular membranes and this leads to baseline toxicity, which is the minimal toxicity any chemical elicits. The critical membrane burden is constant for all chemicals; that is, the dosing concentrations to trigger baseline toxicity decrease with increasing hydrophobicity of the chemicals. Quantitative structure-activity relationships, based on hydrophobicity of chemicals, have been established to predict nominal concentrations causing baseline toxicity in human and mammalian cell lines. However, their applicability is limited to hydrophilic neutral compounds. To develop a prediction model that includes more hydrophobic and charged organic chemicals, a mass balance model was applied for mammalian cells (AREc32, AhR-CALUX, PPARγ-BLA, and SH-SY5Y) considering different bioassay conditions. The critical membrane burden for baseline toxicity was converted into nominal concentration causing 10% cytotoxicity by baseline toxicity (IC10,baseline) using a mass balance model whose main chemical input parameter was the liposome-water partition constants (Klip/w) for neutral chemicals or the speciation-corrected Dlip/w(pH 7.4) for ionizable chemicals plus the bioassay-specific protein, lipid, and water contents of cells and media. In these bioassay-specific models, log(1/IC10,baseline) increased with increasing hydrophobicity, and the relationship started to level off at log Dlip/w around 2. The bioassay-specific models were applied to 392 chemicals covering a broad range of hydrophobicity and speciation. Comparing the predicted IC10,baseline and experimental cytotoxicity IC10, known baseline toxicants and many additional chemicals were identified as baseline toxicants, while the others were classified based on specificity of their modes of action in the four cell lines, confirming excess toxicity of some fungicides, antibiotics, and uncouplers. Given the similarity of the bioassay-specific models, we propose a generalized baseline-model for adherent human cell lines: log[1/IC10,baseline (M)] = 1.23 + 4.97 × (1 - e-0.236 log Dlip/w). The derived models for baseline toxicity may serve for specificity analysis in reporter gene and neurotoxicity assays as well as for planning the dosing for cell-based assays.


Asunto(s)
Compuestos Orgánicos/toxicidad , Línea Celular Tumoral , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Químicos , Compuestos Orgánicos/química , Relación Estructura-Actividad Cuantitativa
17.
Gastroenterology ; 161(5): 1460-1474.e1, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34371000

RESUMEN

BACKGROUND & AIMS: Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, nonmalignant colorectal polyps. We investigated whether underwater endoscopic mucosal resection (UEMR) is superior to CEMR for large (20-40mm) sessile or flat colorectal polyps. METHODS: In this prospective randomized controlled study, patients with sessile or flat colorectal polyps between 20 and 40 mm in size were randomly assigned to UEMR or CEMR. The primary outcome was the recurrence rate after 6 months. Secondary outcomes included en bloc and R0 resection rates, number of resected pieces, procedure time, and adverse events. RESULTS: En bloc resection rates were 33.3% in the UEMR group and 18.4% in the CEMR group (P = .045); R0 resection rates were 32.1% and 15.8% for UEMR vs CEMR, respectively (P = .025). UEMR was performed with significantly fewer pieces compared to CEMR (2 pieces: 45.5% UEMR vs 17.7% CEMR; P = .001). The overall recurrence rate did not differ between both groups (P = .253); however, subgroup analysis showed a significant difference in favor of UEMR for lesions of >30 mm to ≤40 mm in size (P = .031). The resection time was significantly shorter in the UEMR group (8 vs 14 minutes; P < .001). Adverse events did not differ between both groups (P = .611). CONCLUSIONS: UEMR is superior to CEMR regarding en bloc resection, R0 resection, and procedure time for large colorectal lesions and shows significantly lower recurrence rates for lesions >30 mm to ≤40 mm in size. UEMR should be considered for the endoscopic resection of large colorectal polyps.


Asunto(s)
Pólipos Adenomatosos/cirugía , Pólipos del Colon/cirugía , Colonoscopía , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/métodos , Pólipos Adenomatosos/patología , Adulto , Anciano , Anciano de 80 o más Años , Pólipos del Colon/patología , Colonoscopía/efectos adversos , Neoplasias Colorrectales/patología , Resección Endoscópica de la Mucosa/efectos adversos , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tempo Operativo , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral
18.
Med Klin Intensivmed Notfmed ; 116(6): 491-498, 2021 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-34463792

RESUMEN

BACKGROUND: Severe bleeding under antithrombotic therapy is common and challenging in intensive care medicine; on the one hand, rapid bleeding control must be achieved and, on the other hand, thromboembolic complications must be avoided. AIMS: The paper will provide a brief overview of direct oral anticoagulants, therapeutic options and precise instructions for dealing with severe bleeding. RESULTS: In addition to general measures in direct oral anticoagulant (DOAC)-associated major bleeding, prothrombin complex concentrate (PCC), idarucizumab and andexanet alfa are available as specific antidote therapy. In case of bleeding under heparin therapy, protamine sulfate is available as a possible antidote. CONCLUSIONS: In particular, the importance of andexanet alfa in the treatment of factor Xa inhibitor-associated bleeding requires further investigation.


Asunto(s)
Fibrinolíticos , Hemorragia , Administración Oral , Anticoagulantes/efectos adversos , Antídotos/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Fibrinolíticos/efectos adversos , Hemorragia/tratamiento farmacológico , Hemorragia/terapia , Humanos , Proteínas Recombinantes/uso terapéutico
19.
PLoS One ; 16(7): e0254872, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34280238

RESUMEN

BACKGROUND: COVID-19 is only partly understood, and the level of evidence available in terms of pathophysiology, epidemiology, therapy, and long-term outcome remains limited. During the early phase of the pandemic, it was necessary to effectively investigate all aspects of this new disease. Autopsy can be a valuable procedure to investigate the internal organs with special techniques to obtain information on the disease, especially the distribution and type of organ involvement. METHODS: During the first wave of COVID-19 in Germany, autopsies of 19 deceased patients were performed. Besides gross examination, the organs were analyzed with standard histology and polymerase-chain-reaction for SARS-CoV-2. Polymerase chain reaction positive localizations were further analyzed with immunohistochemistry and RNA-in situ hybridization for SARS-CoV-2. RESULTS: Eighteen of 19 patients were found to have died due to COVID-19. Clinically relevant histological changes were only observed in the lungs. Diffuse alveolar damage in considerably different degrees was noted in 18 cases. Other organs, including the central nervous system, did not show specific micromorphological alterations. In terms of SARS-CoV-2 detection, the focus remains on the upper airways and lungs. This is true for both the number of positive samples and the viral load. A highly significant inverse correlation between the stage of diffuse alveolar damage and viral load was found on a case and a sample basis. Mediastinal lymph nodes and fat were also affected by the virus at high frequencies. By contrast, other organs rarely exhibited a viral infection. Moderate to strong correlations between the methods for detecting SARS-CoV-2 were observed for the lungs and for other organs. CONCLUSIONS: The lung is the most affected organ in gross examination, histology and polymerase chain reaction. SARS-CoV-2 detection in other organs did not reveal relevant or specific histological changes. Moreover, we did not find CNS involvement.


Asunto(s)
COVID-19/virología , Sistema Nervioso Central/virología , Pulmón/virología , Ganglios Linfáticos/virología , Carga Viral , Anciano , Anciano de 80 o más Años , Autopsia/estadística & datos numéricos , COVID-19/epidemiología , COVID-19/patología , Sistema Nervioso Central/patología , Femenino , Humanos , Pulmón/patología , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad
20.
Rofo ; 193(10): 1189-1196, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33694145

RESUMEN

PURPOSE: To evaluate imaging patterns of a COVID-19 infection of the lungs on chest radiographs and their value in discriminating this infection from other viral pneumonias. MATERIALS AND METHODS: All 321 patients who presented with respiratory impairment suspicious for COVID-19 infection between February 3 and May 8, 2020 and who received a chest radiograph were included in this analysis. Imaging findings were classified as typical for COVID-19 (bilateral, peripheral opacifications/consolidations), non-typical (findings consistent with lobar pneumonia), indeterminate (all other distribution patterns of opacifications/consolidations), or none (no opacifications/consolidations). The sensitivity, specificity, as well as positive and negative predictive value for the diagnostic value of the category "typical" were determined. Chi² test was used to compare the pattern distribution between the different types of pneumonia. RESULTS: Imaging patterns defined as typical for COVID-19 infections were documented in 35/111 (31.5 %) patients with confirmed COVID-19 infection but only in 4/210 (2 %) patients with any other kind of pneumonia, resulting in a sensitivity of 31.5 %, a specificity of 98.1 %, and a positive and negative predictive value of 89.7 % or 73 %, respectively. The sensitivity could be increased to 45.9 % when defining also unilateral, peripheral opacifications/consolidations with no relevant pathology contralaterally as consistent with a COVID-19 infection, while the specificity decreases slightly to 93.3 %. The pattern distribution between COVID-19 patients and those with other types of pneumonia differed significantly (p < 0.0001). CONCLUSION: Although the moderate sensitivity does not allow the meaningful use of chest radiographs as part of primary screening, the specific pattern of findings in a relevant proportion of those affected should be communicated quickly as additional information and trigger appropriate protective measures. KEY POINTS: · COVID-19 infections show specific X-ray image patterns in 1/3 of patients.. · Bilateral, peripheral opacities and/or consolidations are typical imaging patterns.. · Unilateral, peripheral opacities and/or consolidations should also raise suspicion of COVID-19 infection.. CITATION FORMAT: · Kasper J, Decker J, Wiesenreiter K et al. Typical Imaging Patterns in COVID-19 Infections of the Lung on Plain Chest Radiographs to Aid Early Triage. Fortschr Röntgenstr 2021; 193: 1189 - 1196.


Asunto(s)
COVID-19/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Radiografía Torácica/métodos , Tomografía Computarizada por Rayos X/métodos , Humanos , SARS-CoV-2 , Triaje
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