Publications by authors named "Katharina Rentsch"

168 Publications

Direct Comparison of Clinical Characteristics, Outcomes, and Risk Prediction in Patients with COVID-19 and Controls-A Prospective Cohort Study.

J Clin Med 2021 Jun 17;10(12). Epub 2021 Jun 17.

Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Spitalstrasse 2, 4056 Basel, Switzerland.

Most studies investigating early risk predictors in coronavirus disease 19 (COVID-19) lacked comparison with controls. We aimed to assess and directly compare outcomes and risk predictors at time of emergency department (ED) presentation in COVID-19 and controls. Consecutive patients presenting to the ED with suspected COVID-19 were prospectively enrolled. COVID-19-patients were compared with (i) patients tested negative (overall controls) and (ii) patients tested negative, who had a respiratory infection (respiratory controls). Primary outcome was the composite of intensive care unit (ICU) admission and death at 30 days. Among 1081 consecutive cases, 191 (18%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 890 (82%) were tested negative (overall controls), of which 323 (30%) had a respiratory infection (respiratory controls). Incidence of the composite outcome was significantly higher in COVID-19 (23%) as compared with the overall control group (10%, adjusted-HR 2.45 (95%CI, 1.61-3.74), < 0.001) or the respiratory control group (10%, adjusted-HR 2.93 (95%CI, 1.66-5.17), < 0.001). Blood oxygen saturation, age, high-sensitivity troponin, c-reactive protein, and lactate dehydrogenase were identified as the strongest predictors of poor outcome available at time of ED presentation in COVID-19 with highly comparable prognostic utility in overall and respiratory controls. In conclusion, patients presenting to the ED with COVID-19 have a worse outcome than controls, even after adjustment for differences in baseline characteristics. Most predictors of poor outcome in COVID-19 were not restricted to COVID-19, but of comparable prognostic utility in controls and therefore generalizable to unselected patients with suspected COVID-19.
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http://dx.doi.org/10.3390/jcm10122672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234319PMC
June 2021

Comparison of Acute Kidney Injury in Patients with COVID-19 and Other Respiratory Infections: A Prospective Cohort Study.

J Clin Med 2021 May 25;10(11). Epub 2021 May 25.

Department of Cardiology, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.

Previous studies have indicated an association between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) but lacked a control group. The prospective observational COronaVIrus-surviVAl (COVIVA) study performed at the University Hospital, Basel, Switzerland consecutively enrolled patients with symptoms suggestive of COVID-19. We compared patients who tested positive for SARS-CoV-2 with patients who tested negative but with an adjudicated diagnosis of a respiratory tract infection, including pneumonia. The primary outcome measure was death at 30 days, and the secondary outcomes were AKI incidence and a composite endpoint of death, intensive care treatment or rehospitalization at 30 days. Five hundred and seven patients were diagnosed with respiratory tract infections, and of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. The incidence of AKI was higher in patients with COVID-19 (30% versus 12%, < 0.001), more severe (KDIGO stage 3, 22% versus 13%, = 0.009) and more often required renal replacement therapy (4.4% versus 0.93%; = 0.03). The risk of 30-day mortality and a composite endpoint was higher in patients with COVID-19-associated AKI (adjusted hazard ratio (aHR) mortality 3.98, 95% confidence interval (CI) 1.10-14.46, = 0.036; composite endpoint aHR 1.84, 95% CI 1.02-3.31, = 0.042). The mortality risk was attenuated when adjusting for disease severity (aHR 3.60, 95% CI 0.93-13.96, = 0.062). AKI occurs more frequently and with a higher severity in patients with COVID-19 and is associated with worse outcomes.
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http://dx.doi.org/10.3390/jcm10112288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197451PMC
May 2021

Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men.

J Biol Rhythms 2021 08 23;36(4):384-394. Epub 2021 May 23.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Caffeine intake-particularly in high doses and close to bedtime-may also affect circadian-regulated rapid eye movement (REM) sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 ± 4 years old, habitual caffeine intake 478.1 ± 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 × 150 mg caffeine daily for 10 days), a withdrawal (3 × 150 mg caffeine for 8 days then placebo), and a placebo condition. After 10 days of controlled intake and a fixed sleep-wake cycle, we recorded electroencephalography for 8 h starting 5 h after habitual bedtime (i.e., start on average at 04:22 h which is around the peak of circadian REM sleep promotion). A 60-min evening nap preceded each sleep episode and reduced high sleep pressure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM sleep latency was longer after daily caffeine intake compared with both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was delayed, and volunteers reported more difficulties with awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared with placebo. Our data indicate that besides acute intake, also regular daytime caffeine intake affects REM sleep regulation in men, such that it delays circadian REM sleep promotion when compared with placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.
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http://dx.doi.org/10.1177/07487304211013995DOI Listing
August 2021

Probability of pharmacological target attainment with flucloxacillin in Staphylococcus aureus bloodstream infection: a prospective cohort study of unbound plasma and individual MICs.

J Antimicrob Chemother 2021 06;76(7):1845-1854

Division of Internal Medicine, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland.

Objectives: MSSA bloodstream infections (BSIs) are associated with considerable mortality. Data regarding therapeutic drug monitoring (TDM) and pharmacological target attainment of the β-lactam flucloxacillin are scarce.

Patients And Methods: We determined the achievement of pharmacokinetic/pharmacodynamic targets and its association with clinical outcome and potential toxicity in a prospective cohort of 50 patients with MSSA-BSI. Strain-specific MICs and unbound plasma flucloxacillin concentrations (at five different timepoints) were determined by broth microdilution and HPLC-MS, respectively.

Results: In our study population, 48% were critically ill and the 30 day mortality rate was 16%. The median flucloxacillin MIC was 0.125 mg/L. The median unbound trough concentration was 1.7 (IQR 0.4-9.3), 1.9 (IQR 0.4-6.2) and 1.0 (IQR 0.6-3.4) mg/L on study day 1, 3 and 7, respectively. Optimal (100% fT>MIC) and maximum (100% fT>4×MIC) target attainment was achieved in 45 (90%) and 34 (68%) patients, respectively, throughout the study period. Conversely, when using the EUCAST epidemiological cut-off value instead of strain-specific MICs, target attainment was achieved in only 13 (26%) patients. The mean unbound flucloxacillin trough concentration per patient was associated with neurotoxicity (OR 1.12 per 1 mg/L increase, P = 0.02) and significantly higher in deceased patients (median 14.8 versus 1.7 mg/L, P = 0.01).

Conclusions: Flucloxacillin pharmacological target attainment in MSSA-BSI patients is frequently achieved when unbound flucloxacillin concentrations and strain-specific MICs are considered. However, currently recommended dosing regimens may expose patients to excessive flucloxacillin concentrations, potentially resulting in drug-related organ damage.
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http://dx.doi.org/10.1093/jac/dkab089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212765PMC
June 2021

Disposition Decision Support by Laboratory Based Outcome Prediction.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Emergency Department, University Hospital Basel, 4031 Basel, Switzerland.

Disposition is one of the main tasks in the emergency department. However, there is a lack of objective and reliable disposition criteria, and diagnosis-based risk prediction is not feasible at early time points. The aim was to derive a risk score (TRIAL) based on routinely collected baseline (TRIage level and Age) and Laboratory data-supporting disposition decisions by risk stratification based on mortality. We prospectively included consecutive patients presenting to the emergency department over 18 weeks. Data sets of routinely collected baseline (triage level and age) and laboratory data were used for multivariable logistic regression to develop the TRIAL risk score predicting mortality. Routine laboratory variables and disposition cut-offs were chosen beforehand by expert consensus. Risk stratification was based on low risk (<1%), intermediate risk (1-10%), and high risk (>10%) of in-hospital mortality. In total, 8687 data sets were analyzed. Variables identified to develop the TRIAL risk score were triage level (Emergency Severity Index), age, lactate dehydrogenase, creatinine, albumin, bilirubin, and leukocyte count. The area under the ROC curve for in-hospital mortality was 0.93. Stratification according to the TRIAL score showed that 67.5% of all patients were in the low-risk category. Mortality was 0.1% in low-risk, 3.5% in intermediate-risk, and 26.2% in high-risk patients. The TRIAL risk score based on routinely available baseline and laboratory data provides prognostic information for disposition decisions. TRIAL could be used to minimize admission in low-risk and to maximize observation in high-risk patients.
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http://dx.doi.org/10.3390/jcm10050939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957752PMC
March 2021

Insufficient Stability of Clavulanic Acid in Widely Used Child-Appropriate Formulations.

Antibiotics (Basel) 2021 Feb 23;10(2). Epub 2021 Feb 23.

Paediatric Infectious Diseases, University Children's Hospital Basel, 4056 Basel, Switzerland.

Amoxicillin-clavulanic acid (AMC) belongs to the WHO Essential Medicines List for children, but for optimal antimicrobial effectiveness, reconstituted dry powder suspensions need to be stored in a refrigerated environment. Many patients in low- and middle-income countries who are sold AMC suspensions would be expected not to keep to the specified storage conditions. We aimed to assess the stability of both ingredients in liquid formulations and dispersible tablets, combined with nationally representative data on access to appropriate storage. Degradation of amoxicillin (AMX) and clavulanic-acid (CLA) was measured in suspensions and dispersible tablets commercially available in Switzerland at different ambient temperatures (8 °C vs. 28 °C over 7 days, and 23 °C vs. 28 °C over 24 h, respectively). Data on access to refrigeration and electricity were assessed from the USAID-funded Demographic and Health Survey program. In suspensions, CLA degraded to a maximum of 12.9% (95% CI -55.7%, +29.9%) at 8°C and 72.3% (95% CI -82.8%, -61.8%) at a 28 °C ambient temperature during an observation period of 7 days. Dispersible tablets were observed during 24 h and CLA degraded to 15.4% (95% CI -51.9%, +21.2%) at 23 °C and 21.7% (-28.2%, -15.1%) at a 28 °C ambient temperature. There is relevant degradation of CLA in suspensions during a 7-day course. To overcome the stability challenges for all active components, durable child-appropriate formulations are needed. Until then, prescribers of AMC suspensions or pharmacists who sell the drug need to create awareness for the importance of proper storage conditions regarding effectiveness of both antibiotics and this recommendation should be reflected in the WHO Essential Medicines List for children.
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http://dx.doi.org/10.3390/antibiotics10020225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927114PMC
February 2021

Systematic screening on admission for SARS-CoV-2 to detect asymptomatic infections.

Antimicrob Resist Infect Control 2021 02 27;10(1):44. Epub 2021 Feb 27.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

The proportion of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains elusive and the potential benefit of systematic screening during the SARS-CoV-2-pandemic is controversial. We investigated the proportion of asymptomatic inpatients who were identified by systematic screening for SARS-CoV-2 upon hospital admission. Our analysis revealed that systematic screening of asymptomatic inpatients detects a low total number of SARS-CoV-2 infections (0.1%), questioning the cost-benefit ratio of this intervention. Even when the population-wide prevalence was low, the proportion of asymptomatic carriers remained stable, supporting the need for universal infection prevention and control strategies to avoid onward transmission by undetected SARS-CoV-2-carriers during the pandemic.
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http://dx.doi.org/10.1186/s13756-021-00912-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912536PMC
February 2021

The impact of daily caffeine intake on nighttime sleep in young adult men.

Sci Rep 2021 Feb 25;11(1):4668. Epub 2021 Feb 25.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.
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http://dx.doi.org/10.1038/s41598-021-84088-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907384PMC
February 2021

Accuracy of urine flow cytometry and urine test strip in predicting relevant bacteriuria in different patient populations.

BMC Infect Dis 2021 Feb 25;21(1):209. Epub 2021 Feb 25.

University Hospital Basel, Division of Clinical Bacteriology and Mycology, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

Background: Urinary tract infection (UTI) is diagnosed combining urinary symptoms with demonstration of urine culture growth above a given threshold. Our aim was to compare the diagnostic accuracy of Urine Flow Cytometry (UFC) with urine test strip in predicting bacterial growth and in identifying contaminated urine samples, and to derive an algorithm to identify relevant bacterial growth for clinical use.

Methods: Species identification and colony-forming unit (CFU/ml) quantification from bacterial cultures were matched to corresponding cellular (leucocytes/epithelial cells) and bacteria counts per μl. Results comprise samples analysed between 2013 and 2015 for which urine culture (reference standard) and UFC and urine test strip data (index tests, Sysmex UX-2000) were available.

Results: 47,572 urine samples of 26,256 patients were analysed. Bacteria counts used to predict bacterial growth of ≥10 CFU/ml showed an accuracy with an area under the receiver operating characteristic curve of > 93% compared to 82% using leukocyte counts. The relevant bacteriuria rule-out cut-off of 50 bacteria/μl reached a negative predictive value of 98, 91 and 89% and the rule-in cut-off of 250 bacteria/μl identified relevant bacteriuria with an overall positive predictive value of 67, 72 and 73% for microbiologically defined bacteriuria thresholds of 10, 10 or 10 CFU/ml, respectively. Measured epithelial cell counts by UFC could not identify contaminated urine.

Conclusions: Prediction of a relevant bacterial growth by bacteria counts was most accurate and was a better predictor than leucocyte counts independently of the source of the urine and the medical specialty ordering the test (medical, surgical or others).
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http://dx.doi.org/10.1186/s12879-021-05893-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908726PMC
February 2021

Incidence of major adverse cardiac events following non-cardiac surgery.

Eur Heart J Acute Cardiovasc Care 2020 Oct 14. Epub 2020 Oct 14.

Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University Basel, Basel, Switzerland.

Aims: Major adverse cardiac events (MACE) triggered by non-cardiac surgery are prognostically important perioperative complications. However, due to often asymptomatic presentation, the incidence and timing of postoperative MACE are incompletely understood.

Methods And Results: We conducted a prospective observational study implementing a perioperative screening for postoperative MACE [cardiovascular death (CVD), acute heart failure (AHF), haemodynamically relevant arrhythmias, spontaneous myocardial infarction (MI), and perioperative myocardial infarction/injury (PMI)] in patients at increased cardiovascular risk (≥65 years OR ≥45 years with history of cardiovascular disease) undergoing non-cardiac surgery at a tertiary hospital. All patients received serial measurements of cardiac troponin to detect asymptomatic MACE. Among 2265 patients (mean age 73 years, 43.4% women), the incidence of MACE was 15.2% within 30 days, and 20.6% within 365 days. CVD occurred in 1.2% [95% confidence interval (CI) 0.9-1.8] and in 3.7% (95% CI 3.0-4.5), haemodynamically relevant arrhythmias in 1.2% (95% CI 0.9-1.8) and in 2.1% (95% CI 1.6-2.8), AHF in 1.6% (95% CI 1.2-2.2) and in 4.2% (95% CI 3.4-5.1), spontaneous MI in 0.5% (95% CI 0.3-0.9) and in 1.6% (95% CI 1.2-2.2), and PMI in 13.2% (95% CI 11.9-14.7) and in 14.8% (95% CI 13.4-16.4) within 30 days and within 365 days, respectively. The MACE-incidence was increased above presumed baseline rate until Day 135 (95% CI 104-163), indicating a vulnerable period of 3-5 months.

Conclusion: One out of five high-risk patients undergoing non-cardiac surgery will develop one or more MACE within 365 days. The risk for MACE remains increased for about 5 months after non-cardiac surgery.

Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.
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http://dx.doi.org/10.1093/ehjacc/zuaa008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245139PMC
October 2020

Prevalence and outcome of dysnatremia in patients with COVID-19 compared to controls.

Eur J Endocrinol 2021 Mar;184(3):409-418

Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, Switzerland.

Objective: The pandemic of coronavirus disease (COVID-19) has rapidly spread globally and infected millions of people. The prevalence and prognostic impact of dysnatremia in COVID-19 is inconclusive. Therefore, we investigated the prevalence and outcome of dysnatremia in COVID-19.

Design: The prospective, observational, cohort study included consecutive patients with clinical suspicion of COVID-19 triaged to a Swiss Emergency Department between March and July 2020.

Methods: Collected data included clinical, laboratory and disease severity scoring parameters on admission. COVID-19 cases were identified based on a positive nasopharyngeal swab test for SARS-CoV-2, patients with a negative swab test served as controls. The primary analysis was to assess the prognostic impact of dysnatremia on 30-day mortality using a cox proportional hazard model.

Results: 172 (17%) cases with COVID-19 and 849 (83%) controls were included. Patients with COVID-19 showed a higher prevalence of hyponatremia compared to controls (28.1% vs 17.5%, P < 0.001); while comparable for hypernatremia (2.9% vs 2.1%, P = 0.34). In COVID-19 but not in controls, hyponatremia was associated with a higher 30-day mortality (HR: 1.4, 95% CI: 1.10-16.62, P = 0.05). In both groups, hypernatremia on admission was associated with higher 30-day mortality (COVID-19 - HR: 11.5, 95% CI: 5.00-26.43, P < 0.001; controls - HR: 5.3, 95% CI: 1.60-17.64, P = 0.006). In both groups, hyponatremia and hypernatremia were significantly associated with adverse outcome, for example, intensive care unit admission, longer hospitalization and mechanical ventilation.

Conclusion: Our results underline the importance of dysnatremia as predictive marker in COVID-19. Treating physicians should be aware of appropriate treatment measures to be taken for patients with COVID-19 and dysnatremia.
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http://dx.doi.org/10.1530/EJE-20-1374DOI Listing
March 2021

Epidemiology and precision of SARS-CoV-2 detection following lockdown and relaxation measures.

J Med Virol 2021 04 29;93(4):2374-2384. Epub 2020 Dec 29.

Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.

Objectives: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures.

Methods: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively.

Results: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to <1% in FUP-1, reducing single-test positive predictive values from 99.3% to 85.1%. Following relaxation, rates flared up to 4% and 12% in FUP-2 and -3, but infected patients were younger than during lockdown (34 vs. 52 years, p < .001). In 261 patients providing 936 NOPS, SARS-CoV-2 loads declined by three orders of magnitude within 10 days postdiagnosis (p < .001). SARS-CoV-2 loads in NOPS correlated with those in time-matched lower respiratory fluids or in plasma but remained detectable in some cases with negative follow-up NOPS, respectively.

Conclusion: Manual and automated assays significantly correlated qualitatively and quantitatively. Following a successful lockdown, declining positive predictive values require independent dual-target confirmation for reliable assessment. Confirmatory and quantitative follow-up testing should be obtained within <5 days and consider lower respiratory fluids in symptomatic patients with SARS-CoV-2-negative NOPS.
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http://dx.doi.org/10.1002/jmv.26731DOI Listing
April 2021

LC-MS/MS method for nine different antibiotics.

Clin Chim Acta 2020 Dec 5;511:360-367. Epub 2020 Nov 5.

Laboratory Medicine, University Hospital Basel, University Basel, Petersgraben 4, 4031 Basel, Switzerland. Electronic address:

Background And Aims: TDM of antibiotics can bring benefits to patients and healthcare systems by providing better treatment and saving healthcare resources. We aimed to develop a multi-analyte method for several diverse antibiotics using LC-MS/MS.

Materials And Methods: Sample preparation consisted of protein precipitation with methanol, dilution and online extraction using a Turboflow Cyclone column. Separation was performed on a Synergi 4 µm Max RP column and deuterated forms of three antibiotics were used as internal standards.

Results: We present a LC-MS/MS method for the quantitative determination of nine antibiotics, including five cephalosporins, the carbapenem ertapenem, the fluoroquinolone ciprofloxacin as well as the combination drug trimethoprim-sulfamethoxazole from plasma. Additionally, unbound ertapenem and cefazolin were analyzed in plasma water after ultrafiltration using plasma calibrators. Results from routine TDM show the applicability of the method.

Conclusion: The presented method is precise and accurate and was introduced in a university hospital, permitting fast TDM of all nine analytes. It was also used in a clinical study for measuring cefazolin free and total concentrations.
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http://dx.doi.org/10.1016/j.cca.2020.11.001DOI Listing
December 2020

Ketamine vs. haloperidol for prevention of cognitive dysfunction and postoperative delirium: A phase IV multicentre randomised placebo-controlled double-blind clinical trial.

J Clin Anesth 2021 Feb 22;68:110099. Epub 2020 Oct 22.

Intensive Care Unit, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerland; Department of Clinical Research, University of Basel, Schanzenstrasse 55, 4031 Basel, Switzerland. Electronic address:

Study Objective: Delirium is frequently observed in the postoperative and intensive care unit (ICU) population. Due to the multifactorial origin of delirium and according to international guidelines (e.g., American Geriatrics Society; Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption (PADIS) guideline), there are several but no incontestable options for prevention and symptomatic treatment. The purpose of the Baden PRIDe (Prevention and Reduction of Incidence of postoperative Delirium) trial was to determine whether postoperative cognitive dysfunction and delirium could be prevented by the combination of possible preventive agents such as haloperidol and ketamine. In addition, pre- and postoperative levels of the biomarkers cortisol, neuron specific enolase (NSE) and S100β were measured to investigate their dynamics in delirious and non-delirious patients after surgery.

Design: The Baden PRIDe Trial was an investigator-initiated, phase IV, two-centre, randomised, placebo-controlled, double-blind clinical trial.

Setting: Perioperative care.

Patients: 182 adult patients that underwent elective or emergency surgery under general or combined (i.e., general and regional) anaesthesia.

Interventions: Pre-anaesthetic, pharmacologic prevention of postoperative brain dysfunction with haloperidol, ketamine, and the combination of both vs. placebo.

Measurements: Assessment of cognitive performance pre- and postoperatively with the MMSE, the DOS, the Nursing Delirium Screening Scale (Nu-DESC) or the Intensive Care Delirium Screening Checklist (ICDSC) during ICU stay.

Main Results: None of the three study arms - haloperidol, ketamine, or both drugs combined - was significantly superior to placebo for prevention of postoperative brain dysfunction and delirium (P = 0.39). Measured levels of postoperative cortisol were significantly higher in delirious patients. S-100β levels were significantly higher in all postoperative outcome groups (cognitive impairment, delirium, no cognitive decline), whereas postoperative NSE levels declined in all groups.

Conclusions: The study results offer no possibility for a novel recommendation for prevention of postoperative cognitive decline including delirium. Perioperative S-100β trajectories in patients with cognitive deterioration suggest affection of glial cells in particular.

Trial Registration: ClinicalTrials.govNCT02433041; registered on April 7, 2015.
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http://dx.doi.org/10.1016/j.jclinane.2020.110099DOI Listing
February 2021

Wide awake at bedtime? Effects of caffeine on sleep and circadian timing in male adolescents - A randomized crossover trial.

Biochem Pharmacol 2020 Oct 15:114283. Epub 2020 Oct 15.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland; Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.

Adolescents often suffer from short and mistimed sleep. To counteract the resulting daytime sleepiness they frequently consume caffeine. However, caffeine intake may exaggerate sleep problems by disturbing sleep and circadian timing. In a 28-hour double-blind randomized crossover study, we investigated to what extent caffeine disturbs slow-wave sleep (SWS) and delays circadian timing in teenagers. Following a 6-day ambulatory phase of caffeine abstinence and fixed sleep-wake cycles, 18 male teenagers (14-17 years old) ingested 80 mg caffeine vs. placebo in the laboratory four hours prior to an electro-encephalographically (EEG) recorded nighttime sleep episode. Data were analyzed using both frequentist and Bayesian statistics. The analyses suggest that subjective sleepiness is reduced after caffeine compared to placebo. However, we did not observe a strong caffeine-induced reduction in subjective sleep quality or SWS, but rather a high inter-individual variability in caffeine-induced SWS changes. Exploratory analyses suggest that particularly those individuals with a higher level of SWS during placebo reduced SWS in response to caffeine. Regarding salivary melatonin onsets, caffeine-induced delays were not evident at group level, and only observed in participants exposed to a higher caffeine dose relative to individual bodyweight (i.e., a dose > 1.3 mg/kg). Together, the results suggest that 80 mg caffeine are sufficient to induce alertness at a subjective level. However, particularly teenagers with a strong need for deep sleep might pay for these subjective benefits by a loss of SWS during the night. Thus, caffeine-induced sleep-disruptions might change along with the maturation of sleep need.
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http://dx.doi.org/10.1016/j.bcp.2020.114283DOI Listing
October 2020

Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children.

J Clin Endocrinol Metab 2020 11;105(11)

Pediatric Endocrinology and Diabetology, University Children's Hospital Basel UKBB, University of Basel, Basel, Switzerland.

Context: Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA).

Objective: The objective of this work is to characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA.

Design And Setting: A prospective, observational, multicenter study was conducted.

Patients And Intervention: Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours.

Main Outcome Measures: Measurements included temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), and association between-subject variability (BSV) (coefficient of variation, CV%).

Results: Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95 pmol/L (95% CI, 55-136 pmol/L) (CV%, 158%) to 9.7 pmol/L (95% CI, 8.1-11.4 pmol/L) (CV%, 31%) with a 50% recovery time (t1/2) of 7.1 hours (range, 5.1-11.5 hours) (114%). Serum osmolality decreased from 321 mOsm/kg (range, 315-327 mOsm/kg) (4%) to 294 mOsm/kg (range, 292-296 mOsm/kg) (1%) with a t1/2 of 4.3 hours (range, 3.0-5.6 hours) (64%). Copeptin levels doubled with each osmolality increase by 15 mOsm/kg (range, 10-21 mOsm/kg) (59%), from 9.8 pmol/L (range, 7.3-12.3 pmol/L) (48%) to 280 mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (P = .001), and less between mild vs moderate-severe DKA (P = .04).

Conclusions: First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA.
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http://dx.doi.org/10.1210/clinem/dgaa568DOI Listing
November 2020

Memory CD8 T Cells Balance Pro- and Anti-inflammatory Activity by Reprogramming Cellular Acetate Handling at Sites of Infection.

Cell Metab 2020 09 31;32(3):457-467.e5. Epub 2020 Jul 31.

Department of Biomedicine, Immunobiology, University of Basel, 4031 Basel, Switzerland; Department of Medicine, CITIID, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK. Electronic address:

Serum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8 T cells to produce IFN-γ. Whether acetate modulates memory CD8 T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8 T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly activating glutaminase, thereby augmenting glutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggered calcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducing immunopathology. This indicates that, during different stages of the immune response, the same metabolite-acetate-induces distinct immunometabolic programs within the same cell type.
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http://dx.doi.org/10.1016/j.cmet.2020.07.004DOI Listing
September 2020

Epidemiology of Severe Acute Respiratory Syndrome Coronavirus 2 Emergence Amidst Community-Acquired Respiratory Viruses.

J Infect Dis 2020 09;222(8):1270-1279

Clinical Virology, Laboratory Medicine, University Hospital Basel, Basel, Switzerland.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China as the cause of coronavirus disease 2019 in December 2019 and reached Europe by late January 2020, when community-acquired respiratory viruses (CARVs) are at their annual peak. We validated the World Health Organization (WHO)-recommended SARS-CoV-2 assay and analyzed the epidemiology of SARS-CoV-2 and CARVs.

Methods: Nasopharyngeal/oropharyngeal swabs (NOPS) from 7663 patients were prospectively tested by the Basel S-gene and WHO-based E-gene (Roche) assays in parallel using the Basel N-gene assay for confirmation. CARVs were prospectively tested in 2394 NOPS by multiplex nucleic acid testing, including 1816 (75%) simultaneously for SARS-CoV-2.

Results: The Basel S-gene and Roche E-gene assays were concordant in 7475 cases (97.5%) including 825 (11%) SARS-CoV-2 positives. In 188 (2.5%) discordant cases, SARS-CoV-2 loads were significantly lower than in concordant positive ones and confirmed in 105 (1.4%). Adults were more frequently SARS-CoV-2 positive, whereas children tested more frequently CARV positive. CARV coinfections with SARS-CoV-2 occurred in 1.8%. SARS-CoV-2 replaced CARVs within 3 weeks, reaching 48% of all detected respiratory viruses followed by rhinovirus/enterovirus (13%), influenza virus (12%), coronavirus (9%), respiratory syncytial virus (6%), and metapneumovirus (6%).

Conclusions: Winter CARVs were dominant during the early SARS-CoV-2 pandemic, impacting infection control and treatment decisions, but were rapidly replaced, suggesting competitive infection. We hypothesize that preexisting immune memory and innate immune interference contribute to the different SARS-CoV-2 epidemiology among adults and children.
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http://dx.doi.org/10.1093/infdis/jiaa464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454752PMC
September 2020

Brief validation of the novel GeneXpert Xpress SARS-CoV-2 PCR assay.

J Virol Methods 2020 10 10;284:113925. Epub 2020 Jul 10.

Clinical Bacteriology and Mycology, Laboratory Medicine, University Hospital Basel and University of Basel, Basel, Switzerland; Applied Microbiology Research, Laboratory Medicine, Department Biomedicine, University of Basel, Basel, Switzerland. Electronic address:

The clinical and epidemiologic management of the SARS-CoV-2 pandemic is critically dependent on molecular assays with short turn-around time. We validated the novel Xpert Xpress SARS-CoV-2 assay using a commercial nucleic acid testing (Roche Cobas 6800). We found an excellent concordance over a range of SARS-CoV-2 loads and across established human coronaviruses.
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http://dx.doi.org/10.1016/j.jviromet.2020.113925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351036PMC
October 2020

Early kinetics of cardiac troponin in suspected acute myocardial infarction.

Rev Esp Cardiol (Engl Ed) 2021 Jun 22;74(6):502-509. Epub 2020 May 22.

Department of Cardiology and Cardiovascular Research, Institute Basel (CRIB), University Hospital Basel, Basel, Switzerland. Electronic address:

Introduction And Objectives: Release kinetics of high-sensitivity cardiac troponin (hs-cTn) T and I in patients with acute myocardial infarction (AMI) are incompletely understood. We aimed to assess whether hs-cTnT/I release in early AMI is near linear.

Methods: In a prospective diagnostic multicenter study the acute release of hs-cTnT and hs-cTnI within 1 and 2hours from presentation to the emergency department was quantified using 3 hs-cTnT/I assays in patients with suspected AMI. The primary endpoint was correlation between hs-cTn changes from presentation to 1 hour vs changes from presentation to 2hours, among all AMI patients and different prespecified subgroups. The final diagnosis was adjudicated by 2 independent cardiologists, based on serial hs-cTnT from the serial study blood samples and additional locally measured hs-cTn values.

Results: Among 2437 patients with complete hs-cTnT data, AMI was the adjudicated diagnosis in 376 patients (15%). For hs-cTnT, the correlation coefficient between 0- to 1-hour change and 0- to 2 hour change was 0.931 (95%CI, 0.916-0.944), P <.001. Similar findings were obtained with hs-cTnI (Architect) with correlation coefficients between 0- to 1-hour change and 0- to 2 hour change of 0.969 and hs-cTnI (Centaur) of 0.934 (P <.001 for both). Findings were consistent among type 1 and type 2 AMI and in the subgroup of patients presenting very early after chest pain onset.

Conclusions: Patients presenting with early AMI showed a near linear release of hs-cTnT and hs-cTnI. This near linearity provides the pathophysiological basis for rapid diagnostic algorithms using 0- to 1-hour changes as surrogates for 0- to 2 hour or 0- to 3 hour changes. Registered at ClinicalTrials.gov (Identifier: NCT00470587).
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http://dx.doi.org/10.1016/j.rec.2020.04.008DOI Listing
June 2021

HILIC LC-MS/MS method for the quantification of cefepime, imipenem and meropenem.

J Pharm Biomed Anal 2020 Jul 2;186:113289. Epub 2020 Apr 2.

Laboratory Medicine, University Hospital Basel, University of Basel, Petersgraben 4, 4031 Basel, Switzerland. Electronic address:

A high performance hydrophilic interaction chromatography method combined with tandem-mass spectrometry for the quantification of cefepime, meropenem and imipenem in plasma and cerebrospinal fluid is presented. A solution of 0.5 M 3-Morpholinopropanesulfonic acid and ethylene glycol (1:1) was added to the samples before analysis to ensure stability of analytes during work up and storage. Deuterated forms of cefepime and meropenem were used as internal standards. Protein precipitation prior to injection into the LC-MS/MS system provided a fast and easy sample preparation. For online extraction, a Turboflow Cyclone-MCX column was used and the chromatographic separation was carried out on a Hypersil GOLD HILIC column. Linear calibration curves were obtained in the concentration range of 0.4-40 mg/l, 0.6-60 mg/l and 1-100 mg/l for meropenem, imipenem and cefepime, respectively. The intra- and interday imprecision and inaccuracy values were below 10 % for plasma and 13 % for cerebrospinal fluid using a calibration in plasma. The method was employed for therapeutic drug measurements in a university hospital.
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http://dx.doi.org/10.1016/j.jpba.2020.113289DOI Listing
July 2020

Reproductive number of the COVID-19 epidemic in Switzerland with a focus on the Cantons of Basel-Stadt and Basel-Landschaft.

Swiss Med Wkly 2020 05 4;150:w20271. Epub 2020 May 4.

Department of Biosystems Science and Engineering, ETH Zürich, Switzerland / Swiss Institute of Bioinformatics, Basel, Switzerland.

The reproductive number in Switzerland was between 1.5 and 2 during the first third of March, and has consistently decreased to around 1. After the announcement of the latest strict measure on 20 March 2020, namely that gatherings of more than five people in public spaces are prohibited, the reproductive number dropped significantly below 1; the authors of this study estimate the reproductive number to be between 0.6 and 0.8 in the first third of April.
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http://dx.doi.org/10.4414/smw.2020.20271DOI Listing
May 2020

Drug Exposure in Newborns: Effect of Selected Drugs Prescribed to Mothers During Pregnancy and Lactation.

Ther Drug Monit 2020 04;42(2):255-263

Laboratory Medicine, University Hospital Basel, University Basel, Basel, Switzerland.

The number of newborns exposed to therapeutic drugs during pregnancy is growing because of the increased use of drugs during pregnancy. In recent years, advances in our understanding of drug placental transfer have augmented the likelihood of a healthy baby in mothers with chronic diseases needing drug therapy. Globally, for example, more than 1.4 million pregnancies in 2015 have been burdened with antiretroviral drugs due to an increasing number of HIV-positive women treated with these drugs, particularly in low- and middle-income countries. In most cases, the fetus is exposed to much higher drug doses in utero than the newborn nursed by the mother. Drug transfer through the placenta takes place by passive diffusion, active transport, or facilitated transport, and drug concentrations in the fetal circulation may be comparable to that in the mother's blood concentration. The excretion of drugs into breastmilk predominantly occurs by passive diffusion, allowing only the non-protein-bound fraction of the blood drug concentration to penetrate. Drug agencies in the United States and Europe highly recommend performing clinical trials in pregnant or breastfeeding women. However, only a few drugs have reported statistically sound data in these patient groups. Most available results concerning pregnancy are obtained from observational studies after birth, assessing outcomes in the newborn or by measuring drug concentrations in the mother and umbilical cord blood. In the case of the lactation period, some studies have evaluated drug concentrations in breastmilk and blood of the mother and/or infant. In this review, exposure to antiretrovirals, immunosuppressants used after solid organ transplantation, and antiepileptics during pregnancy and lactation has been discussed in detail.
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http://dx.doi.org/10.1097/FTD.0000000000000747DOI Listing
April 2020

A 2D HPLC-MS/MS method for several antibiotics in blood plasma, plasma water, and diverse tissue samples.

Anal Bioanal Chem 2020 Jan 3;412(3):715-725. Epub 2020 Jan 3.

Laboratory Medicine, University Hospital Basel, University of Basel, Petersgraben 4, 4031, Basel, Switzerland.

An analytical method using 2D high-performance liquid chromatography followed by tandem mass spectrometry for the quantification of the beta-lactam antibiotics amoxicillin, flucloxacillin, piperacillin, benzylpenicillin, the beta-lactamase inhibitors clavulanic acid, and tazobactam, as well as the macrolide antibiotic clindamycin, is presented. All analytes were measured in human plasma, while amoxicillin, clavulanic acid, flucloxacillin, and clindamycin were also analyzed in human tissue samples. Because of its high-protein binding, additionally, the free fraction of flucloxacillin was measured after ultrafiltration. As internal standards, deuterated forms of the beta-lactams were used. Sample preparation for all matrices was protein precipitation followed by online extraction on a TurboFlow MAX column, while sample separation was performed on an Accucore XL C18 column. Calibration curves were linear over 0.2-25 mg/kg for the tissue samples and 0.05-20 mg/l for the free fraction of flucloxacillin. In plasma, the calibration curves for amoxicillin and piperacillin were linear over 3.125-125 mg/l, for clavulanic acid and tazobactam over 1-40 mg/l, for benzylpenicillin 0.25-40 mg/l, and for flucloxacillin and clindamycin over 1.5-60 mg/l and 0.05-8 mg/l respectively. In plasma and plasma ultrafiltrate, inaccuracy and imprecision for any analyte were always less than 15%. In tissue, the accuracy and precision varied up to 16%, respectively, 20%, when various tissues were analyzed using a calibration in water. Graphical abstract.
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http://dx.doi.org/10.1007/s00216-019-02285-0DOI Listing
January 2020

Caffeine-dependent changes of sleep-wake regulation: Evidence for adaptation after repeated intake.

Prog Neuropsychopharmacol Biol Psychiatry 2020 04 19;99:109851. Epub 2019 Dec 19.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland; Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.

Background: Circadian and sleep-homeostatic mechanisms regulate timing and quality of wakefulness. To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, the effects of such a regular intake pattern on circadian sleep-wake regulation are unknown. Thus, we investigated if daily daytime caffeine intake and caffeine withdrawal affect circadian rhythms and wake-promotion in habitual consumers.

Methods: Twenty male young volunteers participated in a randomised, double-blind, within-subject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol.

Results: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both the placebo and caffeine condition.

Conclusions: The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.
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http://dx.doi.org/10.1016/j.pnpbp.2019.109851DOI Listing
April 2020

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

JAMA 2019 12;322(23):2292-2302

Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland.

Importance: Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF).

Objective: To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF.

Design, Setting, And Participants: Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019.

Interventions: Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan.

Main Outcomes And Measures: The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days.

Results: Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%).

Conclusions And Relevance: Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days.

Trial Registration: ClinicalTrials.gov Identifier: NCT00512759.
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http://dx.doi.org/10.1001/jama.2019.18598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990838PMC
December 2019

Danger of Herbal Tea: A Case of Acute Cholestatic Hepatitis Due to Tea.

Front Med (Lausanne) 2019 11;6:221. Epub 2019 Oct 11.

University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.

is a Chinese medicinal herb. Artemisinin-derivatives are recommended as part of a combination treatment for uncomplicated malaria. Herbal and dietary supplements (HDS) are increasingly used worldwide and HDS-induced liver injury is becoming a growing concern. We present the first case of severe acute cholestatic hepatitis due to the intake of tea as chemoprophylaxis for malaria in a patient returning from Ethiopia. The patients presented with jaundice, elevated transaminases, and parameters of cholestasis (total bilirubin 186.6 μmol/L, conjugated bilirubin 168.5 μmol/L). A liver biopsy showed a portal hepatitis with lymphocytic infiltration of the bile ducts and diffuse intra-canalicular and intra-cytoplasmic bilirubinostasis. The toxicologic analysis of the Artemisia tea revealed the ingredients arteannuin b, deoxyartemisin, campher, and scopoletin. There were no other identifiable etiologies of liver disease. The Roussel Uclaf Causality Assessment Method (RUCAM) score assessed a "probably" causal relationship. Sequencing of genes encoding for hepatic transporters for bile acid homeostasis (BSEP, MDR3, and FIC1) found no genetic variants typically associated with hereditary cholestasis syndromes. Normalization of bilirubin occurred 3 months after the onset of disease. The use of artemisinin-derivatives for malaria prevention is ineffective and potentially harmful and should thus be discouraged. Moreover, the case demonstrates our as yet inadequate understanding of the pathophysiology and susceptibility to HDS induced liver injury.
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http://dx.doi.org/10.3389/fmed.2019.00221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798169PMC
October 2019

Relative hypochromia and mortality in acute heart failure.

Int J Cardiol 2019 07 27;286:104-110. Epub 2019 Feb 27.

Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Switzerland. Electronic address:

Background: Relative hypochromia of erythrocytes defined as a reduced mean corpuscular hemoglobin concentration (MCHC) is a surrogate of iron deficiency. We aimed to evaluate the prevalence and prognostic impact of relative hypochromia in acute heart failure (AHF).

Methods: We prospectively characterized 1574 patients presenting with an adjudicated diagnosis of AHF to the emergency department. Relative hypochromia was defined as a MCHC ≤330 g/l and determined at presentation. The presence of AHF was adjudicated by two independent cardiologists. All-cause mortality and AHF-rehospitalization were the primary prognostic end-points.

Results: Overall, 455 (29%) AHF patients had relative hypochromia. Patients with relative hypochromia had higher hemodynamic cardiac stress as quantified by NT-proBNP concentrations (p < 0.001), more extensive cardiomyocyte injury as quantified by high-sensitive cardiac troponin T (hs-cTnT) concentrations (p < 0.001), and lower estimated glomerular filtration rate (eGFR; p < 0.001) as compared to AHF patients without hypochromia. Cumulative incidences for all-cause mortality and AHF-rehospitalization at 720-days were 50% and 55% in patients with relative hypochromia as compared to 33% and 39% in patients without hypochromia, respectively (both p < 0.0001). The association between relative hypochromia and increased mortality (HR 1.7, 95% CI 1.4-2-0) persisted after adjusting for anemia (HR 1.5, 95% CI 1.3-1.8), and after adjusting for hemodynamic cardiac stress (HR 1.46, 95% CI 1.21-1.76) and eGFR (HR 1.5, 95% CI 1.3-1.8, p < 0.001).

Conclusions: Relative hypochromia is common and a strong and independent predictor of increased mortality in AHF. Given the direct link to diagnostic (endoscopy) and therapeutic interventions to treat functional iron deficiency, relative hypochromia deserves increased attention as an inexpensive and universally available biomarker.
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http://dx.doi.org/10.1016/j.ijcard.2019.02.060DOI Listing
July 2019
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