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Myocardial injury after noncardiac surgery (MINS) and perioperative myocardial injury are associated with increased morbidity and mortality. Both are diagnosed by a perioperative increase in troponin, yet there is controversy if MINS is a genuine myocardial insult. We applied postoperative cardiovascular magnetic resonance T2 mapping techniques to visualise acute myocardial injury (i.e. oedema) in six patients with multiple cardiovascular risk factors who underwent aortic surgery. The burden of myocardial oedema was substantially higher in four patients with elevated troponin qualifying for MINS, compared with patients without MINS. The data and images suggest that MINS represents genuine myocardial injury.
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Laboratory tests play a central role in medicine, as they help to make diagnoses, assess prognosis and risk of disease, and monitor therapies, thus contributing to 70% of all medical decisions. This crosssectional function offers great potential for technologic and organizational innovation to influence health care as a whole. In recent years, a variety of technologies have emerged and entered the field of medical research, or even medical care. A new generation of biosensors enables laboratory tests to be carried out at the point of care and allows for faster medical decisions. Modern devices allow for patientcentric blood sampling, which eliminates the need for painful blood draws, patient traveling, and limits the workload of health care professionals. Analytical techniques, such as metabolomics, lipidomics, or proteomics can identify biomarkers extremely sensitively, even down to individual cells. Pharmacogenomics allows for determination of genetic polymorphisms that predict a response to chemotherapeutic agents. Machinelearning approaches can handle large amounts of multilayered data for diagnostic applications. However, this enormous diagnostic potential is far from being utilized and only very few applications have been implemented in clinical practice. Why is this the case? In this article, we describe the key technologic fields, discuss their medical potential, and list obstacles to their implementation. In addition, we present a methodologic framework to support researchers, clinicians, and authorities in development and implementation of novel diagnostic approaches.
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Técnicas Biossensoriais , HumanosRESUMO
BACKGROUND: Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models. METHODS: Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type. RESULTS: Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC (P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01). CONCLUSIONS: Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.
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ABSTRACT: New analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n = 32; HIT ruled out, n = 38; and positive heparin/platelet factor 4 [H/PF4] antibodies, n = 28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using enzyme-linked immunosorbent assay (ELISA) in above mentioned patients and an additional second data set (n = 49). HIT was defined as a positive heparin-induced platelet activation assay (washed platelet assay). Among 98 patients of the primary data set, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive H/PF4 antibodies, and 3 in patients without HIT. The median optical density of a polyspecific H/PF4 ELISA were 3.0, 0.9, and 0.3. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver operating characteristic curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.
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Biomarcadores , Heparina , Proteômica , Trombocitopenia , Humanos , Heparina/efeitos adversos , Feminino , Proteômica/métodos , Masculino , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/sangue , Pessoa de Meia-Idade , Idoso , Selectina-P/sangue , Fator Plaquetário 4 , Adulto , Ativação PlaquetáriaRESUMO
Importance: Heparin-induced thrombocytopenia (HIT) is a life-threatening condition that requires urgent diagnostic clarification. However, knowledge of the diagnostic utility of the recommended diagnostic tests is limited in clinical practice. Objective: To evaluate the current diagnostic practice for managing the suspicion of HIT. Design, Setting, and Participants: This prospective diagnostic study was conducted from January 2018 to May 2021 among consecutive patients with suspected HIT from 11 study centers in Switzerland, Germany, and the United States. Detailed clinical data and laboratory information were recorded. Platelet factor 4/heparin antibodies were quantified using an automated chemiluminescent immunoassay (CLIA). A washed-platelet heparin-induced platelet activation (HIPA) test was used as a reference standard to define HIT. Exposures: Suspicion of HIT. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests. Results: Of 1448 patients included between 2018 and 2021, 1318 were available for the current analysis (median [IQR] age, 67 [57-75] years; 849 [64.6%] male). HIPA was positive in 111 patients (prevalence, 8.4%). The most frequent setting was intensive care unit (487 [37.0%]) or cardiovascular surgery (434 [33.0%]). The 4Ts score was low risk in 625 patients (46.8%). By 2 × 2 table, the numbers of patients with false-negative results were 10 (9.0%; 4Ts score), 5 (4.5%; CLIA), and 15 (13.5%; recommended diagnostic algorithm). The numbers of patients with false-positive results were 592 (49.0%; 4Ts score), 73 (6.0%; CLIA), and 50 (4.1%; recommended diagnostic algorithm), respectively. Conclusions and Relevance: In this diagnostic study of patients suspected of having HIT, when the recommended diagnostic algorithm was used in clinical practice, antibody testing was required in half the patients. A substantial number of patients were, however, still misclassified, which could lead to delayed diagnosis or overtreatment. Development of improved diagnostic algorithms for HIT diagnosis should be pursued.
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Trombocitopenia , Humanos , Masculino , Idoso , Feminino , Estudos Prospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Heparina/efeitos adversos , Algoritmos , AlemanhaRESUMO
In many patients referred with significant bleeding phenotype, laboratory testing fails to define any hemostatic abnormalities. Clinical practice with respect to diagnosis and management of this patient cohort poses significant clinical challenges. We recommend that bleeding history in these patients should be objectively assessed using the International Society on Thrombosis and Haemostasis (ISTH) bleeding assessment tool. Patients with increased bleeding assessment tool scores should progress to hemostasis laboratory testing. To diagnose bleeding disorder of unknown cause (BDUC), normal complete blood count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand factor antigen, von Willebrand factor function, coagulation factors VIII, IX, and XI, and platelet light transmission aggregometry should be the minimum laboratory assessment. In some laboratories, additional specialized hemostasis testing may be performed to identify other rare causes of bleeding. We recommend that patients with a significant bleeding phenotype but normal laboratory investigations should be registered with a diagnosis of BDUC in preference to other terminology. Global hemostatic tests and markers of fibrinolysis demonstrate variable abnormalities, and their clinical significance remains uncertain. Targeted genomic sequencing examining candidate hemostatic genes has a low diagnostic yield. Underlying BDUC should be considered in patients with heavy menstrual bleeding since delays in diagnosis often extend to many years and negatively impact quality of life. Treatment options for BDUC patients include tranexamic acid, desmopressin, and platelet transfusions.
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Hemostasia , Humanos , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea/normas , Hemorragia/terapia , Hemorragia/sangue , Hemorragia/diagnóstico , Transtornos Hemorrágicos/diagnóstico , Transtornos Hemorrágicos/terapia , Transtornos Hemorrágicos/sangue , Fenótipo , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Terminologia como AssuntoRESUMO
BACKGROUND: Supplemental oxygen is used during every general anesthesia. However, for the maintenance phase of a general anesthesia, in most cases the longest part of anesthesia, only scarce evidence of dosing supplemental oxygen exists. Oxygen is a well-known coronary vasoconstrictor and thus may contribute to cardiovascular complications especially in vulnerable high-risk patients with coronary artery disease undergoing major non-cardiac surgery. Myocardial biomarkers are early indicators of myocardial injury. Oxygen supply demand mismatches due to coronary artery disease aggravated by hyperoxia might be displayed by changes from the biomarker's baseline-values. This study is designed to detect changes in myocardial biomarkers levels associated with perioperative hyperoxia. METHODS: This prospective randomized controlled interventional trial investigates the impact of maintaining perioperative high oxygen supplementation in high-risk patients undergoing non-cardiac vascular surgery on cardiac biomarkers, myocardial strain and outcome in 110 patients. Patients are allocated to be supplemented with either 0.3 (normal) or 0.8 (high) fraction of inspired oxygen (FiO2) perioperatively. Included is a short crossover phase during which transesophageal echocardiography is used to evaluate myocardial function at FiO2 0.3 and 0.8 by strain analysis in each patient. Patients will be followed up for complications at 30 days and 1 year. CONCLUSION: The trial is designed to evaluate perioperative changes from baseline myocardial biomarkers associated with perioperative FiO2. Furthermore, exploration and correlation of changes in biomarkers, acute early changes in myocardial function and clinical outcomes induced by different FiO2 may be possible.
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Biomarcadores , Hiperóxia , Oxigenoterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anestesia Geral/métodos , Biomarcadores/metabolismo , Ecocardiografia Transesofagiana , Miocárdio/metabolismo , Oxigênio/metabolismo , Oxigenoterapia/métodos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias , Estudos Prospectivos , Procedimentos Cirúrgicos Vasculares/métodos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Inflammation is a common condition of prostate tissue, whose impact on carcinogenesis is highly debated. Microbial colonization is a well-documented cause of a small percentage of prostatitis cases, but it remains unclear what underlies the majority of sterile inflammation reported. Here, androgen- independent fluctuations of PSA expression in prostate cells have lead us to identify a prominent function of the Transient Receptor Potential Cation Channel Subfamily M Member 8 (TRPM8) gene in sterile inflammation. Prostate cells secret TRPM8 RNA into extracellular vesicles (EVs), which primes TLR3/NF-kB-mediated inflammatory signaling after EV endocytosis by epithelial cancer cells. Furthermore, prostate cancer xenografts expressing a translation-defective form of TRPM8 RNA contain less collagen type I in the extracellular matrix, significantly more infiltrating NK cells, and larger necrotic areas as compared to control xenografts. These findings imply sustained, androgen-independent expression of TRPM8 constitutes as a promoter of anticancer innate immunity, which may constitute a clinically relevant condition affecting prostate cancer prognosis.
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Neoplasias da Próstata , Canais de Cátion TRPM , Humanos , Masculino , Androgênios , Inflamação/genética , Fator Regulador 3 de Interferon , Proteínas de Membrana , NF-kappa B/genética , Neoplasias da Próstata/genética , Receptor 3 Toll-Like/genética , Canais de Cátion TRPM/genética , AnimaisRESUMO
Tumor markers (TM) are crucial in the monitoring of cancer treatment. However, inappropriate requests for screening reasons have a high risk of false positive and negative findings, which can lead to patient anxiety and unnecessary follow-up examinations. We aimed to assess the appropriateness of TM testing in outpatient practice in Switzerland. We conducted a retrospective cohort study based on healthcare claims data. Patients who had received at least one out of seven TM tests (CEA, CA19-9, CA125, CA15-3, CA72-4, Calcitonin, or NSE) between 2018 and 2021 were analyzed. Appropriate determinations were defined as a request with a corresponding cancer-related diagnosis or intervention. Appropriateness of TM determination by patient characteristics and prescriber specialty was estimated by using multivariate analyses. A total of 51,395 TM determinations in 36,537 patients were included. An amount of 41.6% of all TM were determined appropriately. General practitioners most often determined TM (44.3%) and had the lowest number of appropriate requests (27.8%). A strong predictor for appropriate determinations were requests by medical oncologists. A remarkable proportion of TM testing was performed inappropriately, particularly in the primary care setting. Our results suggest that a considerable proportion of the population is at risk for various harms associated with misinterpretations of TM test results.
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BACKGROUND: Currently, assessing the diagnostic performance of new laboratory tests assumes a perfect reference standard, which is rarely the case. Wrong classifications of the true disease status will inevitably lead to biased estimates of sensitivity and specificity. OBJECTIVES: Using Bayesian' latent class models (BLCMs), an approach that does not assume a perfect reference standard, we re-analyzed data of a large prospective observational study assessing the diagnostic accuracy of an antigen test for the diagnosis of SARS-CoV-2 infection in clinical practice. METHODS: A cohort of consecutive patients presenting to a COVID-19 testing facility affiliated with a Swiss University Hospital were recruited (n = 1465). Two real-time PCR tests were conducted in parallel with the Roche/SD Biosensor rapid antigen test on nasopharyngeal swabs. A two-test (PCR and antigen test), three-population BLCM was fitted to the frequencies of paired test results. RESULTS: Based on the BLCM, the sensitivities of the RT-PCR and the Roche/SD Biosensor rapid antigen test were 98.5% [95% CRI 94.8;100] and 82.7% [95% CRI 66.8;100]. The specificities were 97.7% [96.1;99.7] and 99.9% [95% CRI 99.6;100]. CONCLUSIONS: Applying the BLCM, the diagnostic accuracy of RT-PCR was high but not perfect. In contrast to previous results, the sensitivity of the antigen test was higher. Our results suggest that BLCMs are valuable tools for investigating the diagnostic performance of laboratory tests in the absence of perfect reference standard.
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Cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are significant complications in patients with relapsed/refractory diffuse large B-cell lymphoma undergoing chimeric antigen receptor T-cell (CAR-T cell) therapy. However, it remains unclear whether CAR-T cell expression itself is clinically relevant. We assessed CAR-T cell mRNA expression and DNA concentration by digital droplet PCR in peripheral blood from 14 sequential CAR-T cell recipients. Patients were grouped according to CAR-T cell peak expression. Patients with high CAR-T cell peak expression (8 patients; 57%) had higher rates of ICANS (p=0.0308) and intensive care unit admission (p=0.0404), longer durations of hospitalization (p=0.0077), and, although not statistically significant, a higher rate of CRS (p=0.0778). There was a correlation of CAR-T cell mRNA expression with DNA concentration, but CAR-T cell expression levels failed to correlate to response or survival. Our data suggest that higher CAR-T cell peak mRNA expression is associated with increased risk for ICANS and possibly CRS, requiring further investigation in larger studies.
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Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Linfócitos T , Receptores de Antígenos Quiméricos/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Imunoterapia Adotiva/efeitos adversos , RNA Mensageiro/genéticaRESUMO
Gallo et al. assessed the impact of implementing a clinical decision support tool in a multi-hospital setting. This is one of three important points to unlock the capabilities of the next-generation of diagnostic instruments: (a) integrating diagnostic information from various sources, (b) ensuring accurate development and validation in well-designed clinical studies and (c) seamlessly integrating them into clinical practice. Commentary on: Gallo et al. Clinical decision support to reduce unnecessary diagnostic testing for heparin-induced thrombocytopenia. Br J Haematol 2023;202:1011-1017.
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Hematologia , Trombocitopenia , Humanos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnósticoRESUMO
A universal calibrator for the determination of all anti-Xa inhibitors would support laboratory processes. We aimed to test the clinical performance of an anti-Xa assay utilizing a universal edoxaban calibrator to determine clinically relevant concentrations of all anti-Xa inhibitors. Following a pilot study, we enrolled 553 consecutive patients taking rivaroxaban, edoxaban, or apixaban from nine study centers in a prospective cross-sectional study. The Technochrom® anti-Xa assay was conducted using the Technoview® edoxaban calibrator. Using ultra-high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), anti-Xa inhibitor drug concentrations were determined. Sensitivities and specificities to detect three clinically relevant drug concentrations (30 µgL-1, 50 µgL-1, 100 µgL-1) were determined. Overall, 300 patients treated with rivaroxaban, 221 with apixaban, and 32 with edoxaban were included. The overall correlation coefficient (rs) was 0.95 (95% CI 0.94, 0.96). An area under the receiver operating characteristic curve of 0.96 for 30 µgL-1, 0.98 for 50 µgL-1, and 0.99 for 100 µgL-1 was found. The sensitivities were 92.3% (95% CI 89.2, 94.6), 92.7% (89.4, 95.1), and 94.8% (91.1, 97.0), respectively (specificities 82.2%, 93.7%, and 94.4%). In conclusion, the clinical performance of a universal, edoxaban-calibrated anti-Xa assay was solid and most drug concentrations were predicted correctly.
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BACKGROUND: Anecdotal reports suggest that the correlation between heparin/platelet factor 4 (PF4) antibody assays for the diagnosis of heparin-induced thrombocytopenia (HIT) is limited. OBJECTIVES: To investigate the correlation between widely used assays and examine possible factors contributing to variability. METHODS: This is a large, prospective cohort study with 10 participating tertiary care hospitals including 1393 patients with suspected HIT in clinical practice. HIT was defined by a positive heparin-induced platelet activation (HIPA) assay (washed platelet reference standard test). Three different immunoassays were used to measure heparin/PF4 antibodies: chemiluminescent immunoassay, enzyme-linked immunosorbent assay, and particle gel immunoassay. Various factors that could influence the assays were examined: sex (male or female), age (<65 years or ≥65 years), unfractionated heparin exposure, presence of thrombosis, cardiovascular surgery, and intensive care unit. Spearman's correlation coefficients were calculated. Z-scores and diagnostic odds ratios were determined in the aforementioned subgroups of patients. RESULTS: Among 1393 patients, 119 were classified as HIT-positive (prevalence, 8.5%). The median 4Ts score was 5 (IQR, 4-6) in patients with HIT compared with 3 (IQR, 2-4) in patients without HIT. Correlations (rs) between immunoassays were weak (0.53-0.65). Inconsistencies between immunoassays could not be explained by further analyses of z-scored test results and diagnostic odds ratios in subgroups of patients. CONCLUSION: The correlation between widely used heparin/PF4 antibody assays was weak, and key factors could not explain this variability. Standardization of immunoassays is requested to improve comparability.
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Heparina , Trombocitopenia , Humanos , Masculino , Feminino , Idoso , Heparina/efeitos adversos , Fator Plaquetário 4 , Estudos Prospectivos , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Anticorpos , Anticoagulantes/efeitos adversosRESUMO
Background: Diagnosing heparin-induced thrombocytopenia (HIT) at the bedside remains challenging, exposing a significant number of patients at risk of delayed diagnosis or overtreatment. We hypothesized that machine-learning algorithms could be utilized to develop a more accurate and user-friendly diagnostic tool that integrates diverse clinical and laboratory information and accounts for complex interactions. Methods: We conducted a prospective cohort study including 1393 patients with suspected HIT between 2018 and 2021 from 10 study centers. Detailed clinical information and laboratory data were collected, and various immunoassays were conducted. The washed platelet heparin-induced platelet activation assay (HIPA) served as the reference standard. Findings: HIPA diagnosed HIT in 119 patients (prevalence 8.5%). The feature selection process in the training dataset (75% of patients) yielded the following predictor variables: (1) immunoassay test result, (2) platelet nadir, (3) unfractionated heparin use, (4) CRP, (5) timing of thrombocytopenia, and (6) other causes of thrombocytopenia. The best performing models were a support vector machine in case of the chemiluminescent immunoassay (CLIA) and the ELISA, as well as a gradient boosting machine in particle-gel immunoassay (PaGIA). In the validation dataset (25% of patients), the AUROC of all models was 0.99 (95% CI: 0.97, 1.00). Compared to the currently recommended diagnostic algorithm (4Ts score, immunoassay), the numbers of false-negative patients were reduced from 12 to 6 (-50.0%; ELISA), 9 to 3 (-66.7%, PaGIA) and 14 to 5 (-64.3%; CLIA). The numbers of false-positive individuals were reduced from 87 to 61 (-29.8%; ELISA), 200 to 63 (-68.5%; PaGIA) and increased from 50 to 63 (+29.0%) for the CLIA. Interpretation: Our user-friendly machine-learning algorithm for the diagnosis of HIT (https://toradi-hit.org) was substantially more accurate than the currently recommended diagnostic algorithm. It has the potential to reduce delayed diagnosis and overtreatment in clinical practice. Future studies shall validate this model in wider settings. Funding: Swiss National Science Foundation (SNSF), and International Society on Thrombosis and Haemostasis (ISTH).
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Transplante de Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Mieloma Múltiplo , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco de Sangue Periférico , Humanos , Mieloma Múltiplo/terapia , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Transplante Autólogo , Fator Estimulador de Colônias de Granulócitos , BenzilaminasRESUMO
Background: Prevention of recurrent venous thromboembolism (VTE) is considered a main goal of VTE management. However, the extent to which physicians adhere to the recommendations from evidence-based guidelines is unknown. Aim: From a large, prospective clinical cohort, we aimed to (1) quantify the adherence of treatment recommendations to evidence-based guidelines and establish its predictors, and (2) estimate its impact on clinical outcomes and costs in patients with VTE. Methods: We included 6'243 consecutive patients with VTE treated at the university outpatient unit. Detailed clinical characteristics and treatment recommendations were recorded. Adherence of treatment recommendations to evidence-based guidelines at risk assessment was assessed in terms of duration of anticoagulant treatment. Data on death were obtained from the Swiss Central Compensation Office. Health care claims data recorded between 2014 and 2019 were retrieved from Helsana, one of the largest Swiss health insurance companies. Results: The adherence to evidence-based guidelines was 36.1%. Among patients with non-adherence, overtreatment was present in 70.1%. Significant patient-related predictors of guideline adherence were (a) age above 50 years, (b) male sex, (c) pulmonary embolism, (d) unprovoked VTE, (e) multiple VTE, (f) laboratory tests not ordered, and (g) various cardiovascular comorbidities. Non-adherence was not significantly associated with mortality, hospitalization, admission to nursing home, and costs. Conclusions: The adherence to evidence-based guidelines was low, and several unrelated predictors appeared. Although these results need to be confirmed in other settings, they highlight the need for implementation of evidence-based guidelines in clinical practice.
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CME: Rational Laboratory Diagnostics in the Context of COVID-19 Abstract. In the management of COVID-19, a variety of laboratory tests are available to the general practitioner. The choice is difficult, and some of these laboratory tests are discussed controversially in the lay press. In this article, we discuss the important clinical questions and the contribution of laboratory tests to answering these questions. We describe the most common test principles and discuss their diagnostic value. In doing so, we provide the practicing physician with a simple overview for the clinical practice.
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COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico , HumanosRESUMO
Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89-100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57-97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.
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The risk of recurrence after discontinuation of anticoagulation for a combined oral contraceptive (COC)-associated venous thromboembolism (VTE) is unclear. Therefore, we conducted a systematic review and meta-analysis to estimate the incidence of recurrent VTE among women with COC-associated VTE, unprovoked VTE and to compare the incidence of recurrent VTE between the two groups. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase Classic +Embase and Medline ALL to July 2020 and citations from included studies were searched. Randomized controlled trials, prospective cohort studies and meta-analyses of these study types were selected. The analysis was conducted by random-effects model. Nineteen studies were identified including 1537 women [5828 person-years (PY)] with COC-associated VTE and 1974 women (7798 PY) with unprovoked VTE. Studies were at low risk of bias. The incidence rate of VTE recurrence was 1.22/100 PY [95% confidence interval (CI) 0.92-1.62, I2 = 6%] in women with COC-associated VTE, 3.89/100 PY (95% CI 2.93-5.17, I2 = 74%) in women with unprovoked VTE and the unadjusted incidence rate ratio was 0.34 (95% CI 0.26-0.46, I2 = 3%). The recurrence risk in women after COC-associated VTE is low and lower than after an unprovoked VTE.