Publications by authors named "Burkhardt Seifert"

367 Publications

Effect of Collaborative Review of Electronic Patient-Reported Outcomes for Shared Reporting in Breast Cancer Patients: Descriptive Comparative Study.

JMIR Cancer 2021 Mar 17;7(1):e26950. Epub 2021 Mar 17.

ePha Zürich, Zürich, Switzerland.

Background: Digital monitoring of treatment-related symptoms and self-reported patient outcomes is important for the quality of care among cancer patients. As mobile devices are ubiquitous nowadays, the collection of electronic patient-reported outcomes (ePROs) is gaining momentum. So far, data are lacking on the modalities that contribute to the quantity and quality of ePROs.

Objective: The objective of our study was to compare the utilization of two versions of a subsequently employed mobile app for electronic monitoring of PROs and to test our hypothesis that a shared review of symptoms in patient-physician collaboration has an impact on the number of data entries.

Methods: The Consilium Care app engages cancer patients to standardize reporting of well-being and treatment-related symptoms in outpatient settings. For descriptive comparison of the utilization of two slightly different app versions, data were obtained from an early breast cancer trial (version 1 of the app, n=86) and an ongoing study including patients with advanced disease (version 2 of the app, n=106). In both app versions, patients and doctors were allowed to share the information from data entries during consultations. Version 2 of the app, however, randomly selected symptoms that required a detailed and shared regular patient-doctor review in order to focus on the collection and appropriate interpretation regarding awareness and guidance for severity grading. The numbers and types of symptom entries, satisfaction with both app versions, and patients' perceived effects during consultations were included for analysis.

Results: Symptom severity grading was performed according to the Common Terminology Criteria for Adverse Events (CTCAE) using a horizontal slider and was indicated in descriptive terminology in both apps, while a graphical display facilitated the illustration of symptom history charts. In total, 192 patients electronically reported 11,437 data entries on well-being and 33,380 data entries on individual symptoms. Overall, 628 (of 872 intended) requested patient-doctor symptom reviews were performed in version 2 of the app. Both the amount of data entries per patient and day for well-being (version 1 vs version 2: 0.3 vs 1.0; P<.001) and symptoms (version 1 vs version 2: 1.3 vs 1.9; P=.04) appeared significantly increased in version 2 of the app. Overall satisfaction with both app versions was high, although version 2 of the app was perceived to be more helpful in general.

Conclusions: Version 2 of the app showed much better results than version 1 of the app. A request for collaborative patient-doctor symptom review is likely to affect the number of digital symptom data entries. This app shows high potential to improve the patient-doctor experience.

Trial Registration: ClinicalTrials.gov NCT02004496; https://clinicaltrials.gov/ct2/show/NCT02004496 and ClinicalTrials.gov NCT03578731; https://clinicaltrials.gov/ct2/show/NCT03578731.
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http://dx.doi.org/10.2196/26950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088839PMC
March 2021

Prevalence and outcome of contrast-induced nephropathy in major trauma patients.

Eur J Trauma Emerg Surg 2020 Sep 19. Epub 2020 Sep 19.

Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, University of Zurich, Raemistrasse. 100, 8091, Zurich, Switzerland.

Background: Contrast-induced nephropathy (CIN) has been well investigated in patients undergoing coronary angiography, but not in trauma patients. The main aim of this study was to determine the prevalence and to investigate independent risk factors for the development of CIN.

Methods: Between 2008 and 2014, all pre-hospital intubated major trauma patients with documented serum creatinine levels (SCr) undergoing a contrast-enhanced whole-body CT at admission were retrospectively analyzed. CIN was defined as a relative increase in SCr > 25% over the baseline value or an absolute SCr increase of > 44 µmol/l within 72 h. Univariate and multivariable regression analyses were performed to identify significant risk factors. A p value of < 0.01 was considered statistically significant and a p value of 0.01-0.049 suggested evidence.

Results: Of 284 analyzed patients, 41 (14%) met the criteria for CIN. There is suggestive evidence that age and lactate level influenced the development of CIN. Six patients (15%) had hemodialysis in the CIN-group and eight (3.3%) in the group without CIN. Complication and mortality rate was higher in patients with CIN (71% vs. 56% and 32% vs. 23%, respectively). CIN was not an independent risk factor for complications or mortality while controlling for age, gender, injury severity score, and lactate level. The length of stay was not affected by CIN.

Conclusion: CIN occurs frequently in trauma patients, but is not an independent risk factor for complications or mortality. Therefore, contrast enhanced whole-body CT can safely be performed in trauma patients.
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http://dx.doi.org/10.1007/s00068-020-01496-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500990PMC
September 2020

Are the rib fracture score and different computed tomography measures of obesity predictors for mortality in patients with rib fractures? A retrospective cohort study.

Eur J Trauma Emerg Surg 2020 Sep 6. Epub 2020 Sep 6.

Department of Traumatology, University Hospital Zurich, University of Zurich, Ramistrasse 100, 8091, Zurich, Switzerland.

Background: There is missing knowledge about the association of obesity and mortality in patients with rib fractures. Since the global measure of obesity (body mass index [BMI]) is often unknown in trauma patients, it would be convenient to use local computed tomography (CT)-based measures (e.g., umbilical outer abdominal fat) as a surrogate. The purpose of this study was to assess (1) whether local measures of obesity and rib fractures are associated with mortality and abdominal injuries and to evaluate (2) the correlation between local and global measures of obesity.

Materials And Methods: A retrospective cohort study included all inpatients with rib fractures in 2013. The main exposure variable was the rib fracture score (RFS) (number of rib fractures, uni- or bilateral, age). Other exposure variables were CT-based measures of obesity and BMI. The primary outcome (endpoint) was in-hospital mortality. The secondary outcome consisted of abdominal injuries. Sex and comorbidities were adjusted for with logistic regression.

Results: Two hundred and fifty-nine patients (median age 55.0 [IQR 44.0-72.0] years) were analyzed. Mortality was 8.5%. RFS > 4 was associated with 490% increased mortality (OR = 5.9, 95% CI 1.9-16.6, p = 0.002). CT-based measures and BMI were not associated with mortality, rib fractures or injury of the liver. CT-based measures of obesity showed moderate correlations with BMI (e.g., umbilical outer abdominal fat: r = 0.59, p < 0.001).

Conclusions: RFS > 4 was an independent risk factors for increased mortality. Local and global measures of obesity were not associated with mortality, rib fractures or liver injuries. If the BMI is not available in trauma patients, CT-based measures of obesity may be considered as a surrogate.
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http://dx.doi.org/10.1007/s00068-020-01483-1DOI Listing
September 2020

The Mechanisms Responsible for Improved Information Transfer in Avatar-Based Patient Monitoring: Multicenter Comparative Eye-Tracking Study.

J Med Internet Res 2020 03 16;22(3):e15070. Epub 2020 Mar 16.

Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland.

Background: Patient monitoring is central to perioperative and intensive care patient safety. Current state-of-the-art monitors display vital signs as numbers and waveforms. Visual Patient technology creates an easy-to-interpret virtual patient avatar model that displays vital sign information as it would look in a real-life patient (eg, avatar changes skin color from healthy to cyanotic depending on oxygen saturation). In previous studies, anesthesia providers using Visual Patient perceived more vital signs during short glances than with conventional monitoring.

Objective: We aimed to study the deeper mechanisms underlying information perception in conventional and avatar-based monitoring.

Methods: In this prospective, multicenter study with a within-subject design, we showed 32 anesthesia providers four 3- and 10-second monitoring scenarios alternatingly as either routine conventional or avatar-based in random sequence. All participants observed the same scenarios with both technologies and reported the vital sign status after each scenario. Using eye-tracking, we evaluated which vital signs the participants had visually fixated (ie, could have potentially read and perceived) during a scenario. We compared the frequencies and durations of participants' visual fixations of vital signs between the two technologies.

Results: Participants visually fixated more vital signs per scenario in avatar-based monitoring (median 10, IQR 9-11 versus median 6, IQR 4-8, P<.001; median of differences=3, 95% CI 3-4). In multivariable linear regression, monitoring technology (conventional versus avatar-based monitoring, difference=-3.3, P<.001) was an independent predictor of the number of visually fixated vital signs. The difference was less prominent in the longer (10-second) scenarios (difference=-1.5, P=.04). Study center, profession, gender, and scenario order did not influence the differences between methods. In all four scenarios, the participants visually fixated 9 of 11 vital signs statistically significantly longer using the avatar (all P<.001). Four critical vital signs (pulse rate, blood pressure, oxygen saturation, and respiratory rate) were visible almost the entire time of a scenario with the avatar; these were only visible for fractions of the observations with conventional monitoring. Visual fixation of a certain vital sign was associated with the correct perception of that vital sign in both technologies (avatar: phi coefficient=0.358; conventional monitoring: phi coefficient=0.515, both P<.001).

Conclusions: This eye-tracking study uncovered that the way the avatar-based technology integrates the vital sign information into a virtual patient model enabled parallel perception of multiple vital signs and was responsible for the improved information transfer. For example, a single look at the avatar's body can provide information about: pulse rate (pulsation frequency), blood pressure (pulsation intensity), oxygen saturation (skin color), neuromuscular relaxation (extremities limp or stiff), and body temperature (heatwaves or ice crystals). This study adds a new and higher level of empirical evidence about why avatar-based monitoring improves vital sign perception compared with conventional monitoring.
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http://dx.doi.org/10.2196/15070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105929PMC
March 2020

Predictors of blood loss in lung transplant surgery-a single center retrospective cohort analysis.

J Thorac Dis 2019 Nov;11(11):4755-4761

Department of Anesthesiology, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland.

Background: This retrospective study aims to identify clinical predictors of intraoperative blood loss during lung transplantation. While for other surgical specialties predictors of blood loss have been identified such as previous likewise located surgery, poor preoperative health status of patients, blood coagulation status, and use of extra corporeal circulation, predictors of blood loss during lung transplantation are not yet established.

Methods: A total of 326 lung transplants were performed between January 2000 and February 2014 at a tertiary hospital. The primary aim was to associate blood loss with the following potential predictors: pulmonary arterial hypertension, pre- or intraoperative extracorporeal life support (ECLS), previous thoracic surgery, previous lung transplant, and Charlson Comorbidity Index (CCI). Postoperative complications and 30-day mortality were secondary endpoints of the study.

Results: Median estimated blood loss during lung transplant was 1,500 mL (IQR, 1,000-2,875 mL). Pre- and intraoperative ECLS (P=0.02, P<0.001) independently increased blood loss by 59% and 107%, respectively. The higher blood loss during re-transplant marginally missed the significance level (P=0.05). Pulmonary arterial hypertension, previous thoracic surgery and high CCI were not associated with increased blood loss. As secondary outcomes, postoperative complications were more common in patients with a higher blood loss (P=0.04) but was not associated with higher 30-day mortality (P=0.18).

Conclusions: Pre- and intraoperative ECLS were significant risk factors for higher blood loss during lung transplantation. Higher blood loss was associated with higher incidence of postoperative complications but not with a higher 30-day mortality.
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http://dx.doi.org/10.21037/jtd.2019.10.61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940236PMC
November 2019

Implementation of new standard operating procedures for geriatric trauma patients with multiple injuries: a single level I trauma centre study.

BMC Geriatr 2019 12 19;19(1):359. Epub 2019 Dec 19.

Department of Trauma, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Background: The demographic changes towards ageing of the populations in developed countries impose a challenge to trauma centres, as geriatric trauma patients require specific diagnostic and therapeutic procedures. This study investigated whether the integration of new standard operating procedures (SOPs) for the resuscitation room (ER) has an impact on the clinical course in geriatric patients. The new SOPs were designed for severely injured adult trauma patients, based on the Advanced Trauma Life Support (ATLS) and imply early whole-body computed tomography (CT), damage control surgery, and the use of goal-directed coagulation management.

Methods: Single-centre cohort study. We included all patients ≥65 years of age with an Injury Severity Score (ISS) ≥ 9 who were admitted to our hospital primarily via ER. A historic cohort was compared to a cohort after the implementation of the new SOPs.

Results: We enrolled 311 patients who met the inclusion criteria between 2000 and 2006 (group PreSOP) and 2010-2012 (group SOP). There was a significant reduction in the mortality rate after the implementation of the new SOPs (P = .001). This benefit was seen only for severely injured patients (ISS ≥ 16), but not for moderately injured patients (ISS 9-15). There were no differences with regard to infection rates or rate of palliative care.

Conclusions: We found an association between implementation of new ER SOPs, and a lower mortality rate in severely injured geriatric trauma patients, whereas moderately injured patients did not obtain the same benefit.

Trial Registration: Clinicaltrials.gov NCT03319381, retrospectively registered 24 October 2017.
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http://dx.doi.org/10.1186/s12877-019-1380-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923826PMC
December 2019

Standard coagulation assays alone are not sufficient to exclude surgically relevant rivaroxaban plasma concentrations.

Perioper Med (Lond) 2019 20;8:15. Epub 2019 Nov 20.

1Institute of Anaesthesiology, University and University Hospital Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Background: While mainly larger hospitals have introduced routine anti-Xa assays for rivaroxaban (RXA), these are not readily available to smaller hospitals often relying on routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT).The aim of our study was to investigate the effect of RXA plasma concentration on the standard coagulation tests PT (Quick test and INR) and aPTT in a large group of real-life patients. We further assessed whether normal results of these standard coagulation assays are sufficient to exclude surgically relevant RXA plasma concentration, defined as > 50 mcg/l.

Methods: This retrospective study included all patients between 2012 and 2016 where anti-Xa (calibrated for RXA), PT (Quick test and INR), and/or aPTT were determined from the same sample. PT is expressed as Quick value (% of normal plasma pool). In total, 1027 measurements in 622 patients were eligible for analysis: 752 measurements of 505 patients for Quick/INR and 594 measurements of 417 patients for aPTT.

Results: A moderate correlation of PT/Quick (Pearson's correlation coefficient - 0.59; < 0.001), INR (Pearson's correlation coefficient 0.5; < 0.001), and aPTT (Pearson's correlation coefficient 0.53; < 0.001) with RXA plasma concentration was observed. However, in 50% of all samples with a normal PT/Quick, in 25% of all samples with a normal INR and in 80% of all samples with a normal aPTT residual RXA plasma concentration was surgically relevant.

Conclusion: Although a moderate correlation of RXA plasma concentration with PT/Quick, INR, and aPTT was observed, standard coagulation assays are not sufficient to exclude surgically relevant RXA plasma concentrations.
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http://dx.doi.org/10.1186/s13741-019-0128-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864962PMC
November 2019

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

Arterioscler Thromb Vasc Biol 2020 01 26;40(1):279-287. Epub 2019 Nov 26.

Service de cardiologie, Hôpitaux Universitaires de Genève, Switzerland (P. Meyer, J.D.A.).

Objective: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×10 cells/μL emerged as independent predictors for thrombus formation or embolism.

Conclusions: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.
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http://dx.doi.org/10.1161/ATVBAHA.119.313491DOI Listing
January 2020

Iron deficiency is associated with higher mortality in patients undergoing cardiac surgery: a prospective study.

Br J Anaesth 2020 01 24;124(1):25-34. Epub 2019 Oct 24.

Institute of Anaesthesiology, University of Zurich and University Hospital Zurich, Zurich, Switzerland. Electronic address:

Background: Iron deficiency is frequent in patients undergoing cardiac surgery. The relevance of iron deficiency, however, is ill defined. Therefore, our study aimed to investigate the impact of iron deficiency (ferritin <100 μg L) with or without concomitant anaemia on clinical outcome after cardiac surgery.

Methods: In this prospective observational study, 730 patients undergoing elective cardiac surgery were assigned into four groups according to their iron status and anaemia. Mortality, serious adverse events (SAEs), major cardiac and cerebrovascular events (MACCEs), allogenic blood transfusion requirements, and length of hospital stay were assessed during a 90-day follow-up period. The effect of iron deficiency on these outcomes was first calculated in models adjusting for anaemia only, followed by two multivariate models adjusting for anaemia and either the EuroSCORE II or any possible confounders.

Results: The presence of iron deficiency (ferritin <100 μg L) was associated with an increase in 90-day mortality from 2% to 5% in patients without anaemia, and from 4% to 14% in patients with anaemia. Logistic regression resulted in an odds ratio of 3.5 (95% confidence interval: 1.5-8.4); P=0.004. The effect persisted in both multivariate models. Moreover, iron deficiency was associated with an increased incidence of SAEs, MACCEs, transfusion, and prolonged hospital stay.

Conclusions: Preoperative iron deficiency (ferritin <100 μg L) was independently associated with increased mortality, more SAEs, and prolonged hospital stay after cardiac surgery. These findings underline the importance of preoperative iron deficiency screening in the context of a comprehensive patient blood management programme, and highlight its importance as a research topic in cardiac surgery.

Clinical Trial Registration: NCT02031289.
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http://dx.doi.org/10.1016/j.bja.2019.09.016DOI Listing
January 2020

Intracavitary cisplatin-fibrin chemotherapy after surgery for malignant pleural mesothelioma: A phase I trial.

J Thorac Cardiovasc Surg 2019 Aug 22. Epub 2019 Aug 22.

Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland.

Objectives: Intracavitary chemotherapy is a promising concept to improve local tumor control for malignant pleural mesothelioma with reported high morbidity rates. We have demonstrated that administration of cisplatin loaded to fibrin increased local drug concentration and reduced systemic toxicity in preclinical models. We present a phase I trial of intracavitary cisplatin-fibrin after surgical tumor resection.

Methods: A total of 12 patients (75% International Mesothelioma Interest Group stage III-IV) were treated with 4 dose levels of intracavitary cisplatin-fibrin (11-44 mg/m body surface area) in a dose-escalating design. Cisplatin-fibrin was sprayed on the resected surfaces after pleurectomy/decortication. Blood and tissue samples were taken to assess toxicity and pharmacokinetics. Patients were regularly followed up.

Results: No dose-limiting toxicity was observed. Major morbidity occurred in 4 patients (33%). The 30-day and 90-day mortality were both 0%. Of 80 adverse events, 9 were classified serious, but none of these were related to study treatment. Local cisplatin concentration in the chest wall tissue was high at all dose levels (median, 46.3 μg/g [12-133 μg/g]). In serum, median cisplatin area under the concentration time curve values were always below renal toxicity levels. The median overall survival with 95% confidence interval was 21 months (10-31 months). In 1 patient with epithelioid malignant pleural mesothelioma (International Mesothelioma Interest Group stage I), there was no sign of relapse 48 months after treatment (44 mg/m body surface area).

Conclusions: The administration of intracavitary cisplatin-fibrin is safe with favorable pharmacokinetics. Although most patients had advanced disease, long-term outcomes are comparable to other multimodal concepts. A confirmation phase II trial is ongoing.
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http://dx.doi.org/10.1016/j.jtcvs.2019.07.073DOI Listing
August 2019

Risk factors for central line-associated bloodstream infections in children with tunneled central venous catheters.

Am J Infect Control 2020 01 6;48(1):33-39. Epub 2019 Aug 6.

Division of Infectious Diseases and Hospital Epidemiology and Children's Research Center, University Children's Hospital Zürich, Zürich, Switzerland.

Background: Central line-associated bloodstream infections (CLABSIs) are among the most common complications of central venous catheters (CVCs). The aim of this study was to examine the epidemiology of CLABSIs in tunneled CVCs and analyze their risk factors in a general pediatric population.

Methods: Children with a tunneled CVC inserted at the University Children's Hospital Zürich between January 2009 and December 2015 were eligible for the study. The influence of CVC dwell time on the risk of CLABSI was examined using life tables. Hazard ratios (HRs) for CLABSIs were analyzed using Cox regression for age and diagnosis with cluster robust standard errors.

Results: Fifty-five CLABSIs were observed in 193 patients with 284 tunneled CVCs. Overall, CVCs in children with gastrointestinal disorders and in children 2 to 5 years of age showed the highest incidence rates of 6.06 and 5.85 CLABSIs per 1,000 catheter days, respectively, during the first 90 days after placement. Gastrointestinal disease (HR, 3.89; 95% CI, 2.19-6.90; P < .001) and age 2 to 5 years (HR, 2.48; 95% CI, 1.45-4.22; P = .001) were identified as independent risk factors for CLABSI. In children without gastrointestinal disease, tunneled CVCs showed an increasing risk of CLABSI after a dwell time of 90 days.

Conclusions: The need for tunneled CVCs requires the evaluation of targeted CLABSI prevention measures, especially in young children with underlying gastrointestinal disease.
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http://dx.doi.org/10.1016/j.ajic.2019.06.027DOI Listing
January 2020

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry.

J Am Heart Assoc 2019 08 17;8(15):e010881. Epub 2019 Jul 17.

Clinic for Cardiology and Pneumology Georg August University Goettingen Goettingen Germany.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.
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http://dx.doi.org/10.1161/JAHA.118.010881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761645PMC
August 2019

Detrusor overactivity is missed by stopping urodynamic investigation at a bladder volume of 500 mL.

BJU Int 2019 11 1;124(5):870-875. Epub 2019 Aug 1.

Department of Neuro-Urology, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.

Objectives: To investigate whether detrusor overactivity (DO) is missed in a relevant percentage of patients if the urodynamic investigation (UDI) is stopped at a filling volume of 500 mL due to the fear of bladder overdistention, in patients with lower urinary tract symptoms and high bladder capacity.

Patients And Methods: A consecutive series of 1598 patients with a bladder capacity of >500 mL in the bladder diary undergoing UDI due to lower urinary tract dysfunction (LUTD) was prospectively investigated. UDI was performed according to Good Urodynamic Practices recommended by the International Continence Society. UDI was stopped at strong desire to void or in case of autonomic dysreflexia, vesico-uretero-renal reflux, bladder pain or discomfort.

Results: Of the 1598 patients (594 women, 1004 men), 1282 (80%) and 316 (20%) had neurogenic and non-neurogenic LUTD, respectively. Overall, DO was detected in 66% (1048/1598), in 71% (910/1282) with neurogenic and in 44% (138/316) with non-neurogenic LUTD. DO occurred in 16% (263/1598, 95% confidence interval [CI] 14.7-18.4%) only at a bladder volume >500 mL. This phenomenon was significantly (P < 0.001) more frequent in patients with neurogenic (18% [236/1282], 95% CI 16.4-20.6%) compared with non-neurogenic (9% [27/316], 95% CI 5.9-12.1%) LUTD.

Conclusions: In both neurological and non-neurological patients with high bladder capacity, we strongly recommend not to stop UDI at a bladder volume of 500 mL, as DO might be missed in a relevant percentage leading to inappropriate patient treatment.
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http://dx.doi.org/10.1111/bju.14868DOI Listing
November 2019

Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry.

Eur Heart J 2019 07;40(26):2142-2151

Department of Internal Medicine/Cardiology, University of Leipzig-Heart Center, Leipzig, Germany.

Aims: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS).

Methods And Results: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission.

Conclusions: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.
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http://dx.doi.org/10.1093/eurheartj/ehz170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612368PMC
July 2019

Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial.

Lancet 2019 06 26;393(10187):2201-2212. Epub 2019 Apr 26.

Department of Cardiothoracic and Vascular Surgery, German Heart Centre Berlin, Berlin, Germany; German Centre for Cardiovascular Research, Berlin, Germany; Department of Cardiothoracic Surgery, Charité - Universitätsmedizin Berlin Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Anaemia and iron deficiency are frequent in patients scheduled for cardiac surgery. This study assessed whether immediate preoperative treatment could result in reduced perioperative red blood cell (RBC) transfusions and improved outcome.

Methods: In this single-centre, randomised, double-blind, parallel-group controlled study, patients undergoing elective cardiac surgery with anaemia (n=253; haemoglobin concentration (Hb) <120 g/L in women and Hb <130 g/L in men) or isolated iron deficiency (n=252; ferritin <100 mcg/L, no anaemia) were enrolled. Participants were randomly assigned (1:1) with the use of a computer-generated range minimisation (allocation probability 0·8) to receive either placebo or combination treatment consisting of a slow infusion of 20 mg/kg ferric carboxymaltose, 40 000 U subcutaneous erythropoietin alpha, 1 mg subcutaneous vitamin B12, and 5 mg oral folic acid or placebo on the day before surgery. Primary outcome was the number of RBC transfusions during the first 7 days. This trial is registered with ClinicalTrials.gov, number NCT02031289.

Findings: Between Jan 9, 2014, and July 19, 2017, 1006 patients were enrolled; 505 with anaemia or isolated iron deficiency and 501 in the registry. The combination treatment significantly reduced RBC transfusions from a median of one unit in the placebo group (IQR 0-3) to zero units in the treatment group (0-2, during the first 7 days (odds ratio 0·70 [95% CI 0·50-0·98] for each threshold of number of RBC transfusions, p=0·036) and until postoperative day 90 (p=0·018). Despite fewer RBC units transfused, patients in the treatment group had a higher haemoglobin concentration, higher reticulocyte count, and a higher reticulocyte haemoglobin content during the first 7 days (p≤0·001). Combined allogeneic transfusions were less in the treatment group (0 [IQR 0-2]) versus the placebo group (1 [0-3]) during the first 7 days (p=0·038) and until postoperative day 90 (p=0·019). 73 (30%) serious adverse events were reported in the treatment group group versus 79 (33%) in the placebo group.

Interpretation: An ultra-short-term combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12, and oral folic acid reduced RBC and total allogeneic blood product transfusions in patients with preoperative anaemia or isolated iron deficiency undergoing elective cardiac surgery.

Funding: Vifor Pharma and Swiss Foundation for Anaesthesia Research.
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http://dx.doi.org/10.1016/S0140-6736(18)32555-8DOI Listing
June 2019

Does Coffee Intake Reduce Postoperative Ileus After Laparoscopic Elective Colorectal Surgery? A Prospective, Randomized Controlled Study: The Coffee Study.

Dis Colon Rectum 2019 08;62(8):997-1004

Department for General, Visceral and Vascular Surgery, Kantonsspital Baden, Baden, Switzerland.

Background: Postoperative ileus after colorectal surgery is a frequent problem that significantly prolongs hospital stay and increases perioperative costs.

Objective: The aim was to evaluate the effect of standardized coffee intake on postoperative bowel movement after elective laparoscopic colorectal resection.

Design: This is a prospective randomized controlled trial that was conducted between September 2014 and December 2016.

Settings: This study was performed in a public cantonal hospital in Switzerland with accreditation for colon and rectum cancer surgery.

Patients: Patients who underwent elective colorectal surgery were included.

Interventions: Patients were randomly assigned either to the intervention group receiving coffee or the control group receiving tea. A total of 150 mL of the respective beverage was drunk 3 times per day every postoperative day until discharge.

Main Outcome Measures: The primary end point was time to first bowel movement. Secondary end points included the use of laxative, insertion of a nasogastric tube, length of hospital stay, and postoperative complications.

Results: A total of 115 patients were randomly assigned: 56 were allocated to the coffee group and 59 to the tea group. After coffee intake, the first bowel movement occurred after a median of 65.2 hours versus 74.1 hours in the control group (intention-to-treat analysis; p = 0.008). The HR for earlier first bowel movement after coffee intake was 1.67 (p = 0.009). In the per-protocol analysis, hospital stay was shorter in the coffee group (6 d in the coffee group vs 7 d in the tea group; p = 0.043).

Limitations: The rate of protocol violation, mostly coffee consumption in the tea arm, was relatively high, even if patients were clearly instructed not to consume coffee if they were in the tea arm.

Conclusions: Coffee intake after elective laparoscopic colorectal resection leads to faster recovery of bowel function. Therefore, coffee intake represents a simple and effective strategy to prevent postoperative ileus. See Video Abstract at http://links.lww.com/DCR/A955.

Trial Registration: clinicaltrials.gov identifier: NCT02469441.
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http://dx.doi.org/10.1097/DCR.0000000000001405DOI Listing
August 2019

Cardiac biomarkers but not measures of vascular atherosclerosis predict mortality in patients with peripheral artery disease.

Clin Chim Acta 2019 Aug 11;495:215-220. Epub 2019 Apr 11.

Angiology, KliniK im Park, Zurich, Switzerland.

Background: Peripheral artery disease (PAD) becomes more prevalent with advancing age and is associated with elevated risk of cardiovascular events and shortened life expectancy. We investigated the prognostic performance of cardiac and vascular biomarkers in a cohort of PAD patients.

Methods: A total of 95 PAD patients were enrolled (mean age 68 years, range 47 to 86 years, 73 males). Carotid intima-media thickness (cIMT), ankle brachial index (ABI), high sensitive cardiac troponin T, and N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) were measured.

Results: During a median follow-up time of 9.5 years, 44 patients died and 51 patients survived. Upon Kaplan-Meier survival analysis hs-TnT (P < .001) or NT-proBNP levels (P < .001) above the median but not cIMT above the median (P = .488) or ABI below the median (P < .436)were associated with reduced survival rate. Upon univariate cox regression and after adjustment for age, gender, prior cerebral artery disease, and diabetes mellitus only the association between hs-cTnT and mortality remained significant (HR 1.93, 95% CI 1.33-2.79, P < .001). In receiver operating curve analysis hs-cTnT (area under the curve [AUC]: 0.77, 95% CI: 0.67-0.87, P < .001) NT-proBNP (AUC: 0.74, 95% CI: 0.64-0.84, P < .001) as well as hs-cTnT, and NT-proBNP combined (AUC: 0.79, 95% CI: 0.69-0.88, P < .001) were superior to cIMT (AUC: 0.64, 95%, CI: 0.53-0.76, P = .022) and ABI (AUC: 0.57, 95% CI: 0.44-0.68, P = .313) in discriminating risk for mortality.

Conclusion: hs-cTnT and NT-proBNP should be taken into account for prognosis of patients with PAD.
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http://dx.doi.org/10.1016/j.cca.2019.04.061DOI Listing
August 2019

Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.

J Inherit Metab Dis 2019 03 17;42(2):333-352. Epub 2019 Feb 17.

Hospital Infantil Miguel Servet, Zaragoza, Spain.

Aim: To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry.

Results: This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities.

Conclusion: Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.
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http://dx.doi.org/10.1002/jimd.12041DOI Listing
March 2019

Skeletonized internal thoracic artery harvesting: a low thermal damage electrosurgical device provides improved endothelial layer and tendency to better integrity of the vessel wall compared to conventional electrosurgery.

J Cardiothorac Surg 2018 Oct 11;13(1):105. Epub 2018 Oct 11.

Department of Cardiac Surgery, University Hospital Zurich, Rämistrasse 100, 8001, Zurich, Switzerland.

Background: Electrosurgery is fundamental to the precise, fast and bloodless preparation of internal thoracic artery grafts in cardiac surgery. The PEAK PlasmaBlade is a monopolar electrosurgical device that uses pulsed radiofrequency energy to generate a plasma-mediated discharge along an insulated electrode, creating a cutting edge while the blade stays near body temperature. The aim of this study is to compare the histological samples, cardiac computed-tomography of graft patency, and clinical outcomes of patients after off-pump coronary artery bypass grafting with preparation of the internal thoracic arteries by a conventional electrosurgical device and the PlasmaBlade.

Methods: In twenty subjects one internal thoracic artery was prepared with PlasmaBlade and the other artery with a conventional electrosurgical device. Histological samples were evaluated for three factors for potential graft failure: endothelial damage, integrity of the vessel wall and adventitial hemorrhage. Five samples per artery were evaluated by a novel scoring method based on the exposed circumference of the histological sample ("0": 0%, "1": 1-25%, "2": 26-50%, "3": 51-75%, "4": ≥76% of the circumference). The Wilcoxon signed ranks test for mean scores within subjects was performed. Six-month-follow up by cardiac computed tomography for evaluation of graft patency was completed in 16 patients.

Results: Histological results demonstrated significantly less endothelial damage after PlasmaBlade (83% vs 60%, absolute: 75/90 vs. 53/89 samples with score "0-1", p = 0.04). PlasmaBlade samples demonstrated a tendency to better wall integrity (72% vs. 54%, absolute: 64/89 vs. 47/87 samples with score "0-1", p = 0.32). There were no differences in endothelial bleeding (PlasmaBlade 46% vs. electrosurgery 53%, absolute: 41/88 vs. 48/90 samples with score "0-1", p = 0.63). Computed tomography confirmed non-inferiority of the PlasmaBlade to conventional electrosurgery with a patency rate of 94%.

Conclusion: Histologically, internal thoracic arteries harvested with PlasmaBlade demonstrate a more intact endothelial layer and a tendency to better wall integrity. Computed tomography of graft patency speaks for non-inferiority to conventional electrosurgery. PlasmaBlade may be preferable to conventional electrosurgery, if further follow-up confirms patency of internal thoracic arteries.

Trial Registration: NCT03510026 , registered 4th April 2018 (retrospectively registered).
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http://dx.doi.org/10.1186/s13019-018-0797-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180394PMC
October 2018

Treatment of non-alcoholic steatohepatitis patients with vitamin D: a double-blinded, randomized, placebo-controlled pilot study.

Scand J Gastroenterol 2018 Sep 29;53(9):1114-1120. Epub 2018 Sep 29.

c Clinical Trials Center, University Hospital Zurich , Zurich , Switzerland.

Background: Non-alcoholic steatohepatitis (NASH) is defined by liver inflammation and consecutive fibrotic damage caused by a deposition of fat in the liver. No licensed medical treatments exist and lifestyle modification is difficult to incorporate into everyday life. We investigated the efficacy and safety of a 48-week treatment with vitamin D3 in NASH patients.

Methods: Histologically determined NASH patients with elevated alanine aminotransferase (ALT) and decreased 25-OH vitamin D level at baseline received vitamin D3 or placebo orally over a 48-week period. The primary endpoint of this study was the change in ALT from baseline to the end-of-treatment. Steatohepatitis was categorized according to the Steatosis, Activity and Fibrosis Score and disease activity was assessed using the NAFLD activity score.

Results: Serum 25-OH vitamin D levels significantly increased only in the vitamin D3 group over the 48-week treatment phase indicating compliance. In contrast to placebo, patients in the vitamin D group had markedly decreased ALT levels after the end-of-treatment phase. A significant decrease during treatment with vitamin D was also observed for cytokeratin-18 fragments compared with placebo. The study was not powered to detect changes in histological score, hence only descriptive results for histopathological characteristics are available.

Conclusions: Treatment with 2100 IE vitamin D q.d. over 48 weeks was well tolerated and led to a significant improvement of serum ALT levels in patients with hypovitaminosis D and histology-proven NASH as the primary endpoint together with a trend toward reduction of hepatic steatosis, which was not significant due to a small number of available biopsy specimens.
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http://dx.doi.org/10.1080/00365521.2018.1501091DOI Listing
September 2018

Intraoperative unfolding and postoperative pruning of the pituitary gland after transsphenoidal surgery for pituitary adenoma: A volumetric and endocrinological evaluation.

Endocrine 2019 02 21;63(2):231-239. Epub 2018 Sep 21.

Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Purpose: To describe the volumetric changes that the pituitary gland (PG) undergoes during and after transsphenoidal surgery (TSS), and to evaluate if unfolding and/or pruning are related to endocrinological outcome measures.

Methods: Retrospective evaluation of data prospectively collected of a cohort of patients undergoing TSS for a pituitary adenoma with the adjunctive use of high field 3 Tesla intraoperative MRI. All patients underwent a full endocrinological workup preoperatively, as well as at 6 weeks and 1 year postoperatively. A decrease in PG volume ≥15% between the intraoperative and 3-month, or between the 3-month and 12-month measurements, was considered early and late pruning, respectively.

Results: The PG unfolds significantly during TSS, and subsequently undergoes pruning up until 1 year postoperatively, in most cases returning to the preoperatively measured PG volume. A smaller baseline PG volume predicts intraoperative unfolding. Early pruning of the PG after surgery was associated with new functional deficits. Baseline pituitary compression also correlated to newly occurring deficits after surgery. A larger 1-year pituitary volume was associated with biochemical remission in secreting adenomas.

Conclusions: The PG shows dynamic change during and after TSS for pituitary adenoma. Small baseline and 3-month PG volumes, as well as early pruning were independently associated with new deficits. Our findings warrant prospective validation in a larger cohort with higher statistical power.
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http://dx.doi.org/10.1007/s12020-018-1758-2DOI Listing
February 2019

Fast-Track Management in Off-Pump Coronary Artery Bypass Grafting: Dexmedetomidine Provides Rapid Extubation and Effective Pain Modulation.

Thorac Cardiovasc Surg 2019 Sep 28;67(6):450-457. Epub 2018 Aug 28.

Department of Cardiac Surgery, Stadtspital Triemli, Zürich, Switzerland.

Background:  Dexmedetomidine (DEX) is a highly selective α-2 agonist with many desirable effects including analgesia, improvement of hemodynamic stability, and potential myocardial and renal protection. The aim of this study was to investigate the effect of DEX on patients undergoing off-pump coronary artery bypass (OPCAB) grafting with regard to less pain medication, earlier extubation, faster transfer to normal ward, and cardiac protection.

Patients And Methods:  From January 2012 to March 2015, 464 patients receiving OPCAB were included for retrospective analysis. After propensity matching (1:1), two groups (DEX vs. propofol,  = 129) could be compared. Continuous and categorical variables were reported as mean ± standard deviation or percentages, and compared with the chi-square test and the Mann-Whitney's test, respectively.

Results:  In the DEX group, less use of pain medication in the initial phase at intensive care unit was observed. During the first 2 hours, DEX patients received more nicomorphine (DEX 8 ± 3.2 mg vs. propofol 6 ± 4 mg,  < 0.001), while in the following 2 hours, the pain medication was significantly reduced (DEX 3.2 ± 2.8 mg vs. propofol 4.7 ± 3.3 mg,  < 0.001). Remifentanil was stopped considerably earlier (DEX 238 ± 209 minutes vs. propofol 353 ± 266 minutes,  < 0.001). DEX led to earlier extubation (DEX 208 ± 106 minutes vs. propofol 307 ± 230 minutes,  < 0.001) and less postoperative atrial fibrillation (AF) ( = 0.01).

Conclusion:  Early postoperative DEX application supports the fast-track strategy in patients after OPCAB through enabling rapid extubation, effective pain control, and reduced occurrence of new-onset AF. We are confident to give precedence to DEX over propofol as the new routine medication during postoperative patient transfer.
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http://dx.doi.org/10.1055/s-0038-1668602DOI Listing
September 2019

Predictors for shorter and longer length of hospital stay outliers: a retrospective case-control study of 8247 patients at a university hospital trauma department.

Swiss Med Wkly 2018 Aug 22;148:w14650. Epub 2018 Aug 22.

Medical Directorate, University Hospital Zurich, University of Zurich, Switzerland.

Background: Providing efficient healthcare is important for hospitals. Shorter and longer length of hospital stay (LOS) outliers influence financial results and reimbursement. The objective of this study was to identify independent diagnosis related group (DRG)-related risk factors for shorter and longer LOS outlier status.

Methods: A retrospective case-control study was conducted at a Swiss level 1 trauma centre between January 2012 and December 2014. The study included all patients with available information on LOS based on DRG. Many predictor variables were tested. The outcome variable was the DRG-based LOS. Logistic regression models were fitted for shorter and longer LOS outliers, with a significance level of <1%.

Results: A total of 8247 patients were analysed, of whom inliers were more frequent than shorter and longer LOS outliers (n = 5838 [70.8%] vs n = 1996 [24.2%] vs n = 413 [5.0%]). Predictors for shorter LOS outliers were death (odds ratio [OR] 4.89, 95% confidence interval [CI] 3.27-7.31), concussion (OR 4.87, 95% CI 4.20-5.63) and psychiatric disease (OR 1.85, 95% CI 1.46-2.34). Predictors for longer LOS outliers were age ≥65 years (OR 1.74, 95% CI 1.31-2.30), number of diagnoses ≥5 (OR 2.07, 95% CI 1.52-2.81), comorbidity (OR 1.75, 95% CI 1.28-2.40), number of surgical procedures (OR 1.76, 95% CI 1.36-2.28), complication perioperatively (OR 1.69, 95% CI 1.24-2.30), infection (OR 2.66, 95% CI 1.57-4.49]), concussion (OR 1.52, 95% CI 1.14-2.01) and urinary tract infection (OR 2.34, 95% CI 1.61-3.41).

Conclusion: This large study showed that LOS outliers, especially shorter LOS outliers, are relatively common. Patients who died, or had concussion or psychiatric disease were more commonly discharged early. Patients weremore often discharged late if they were aged ≥65 years, had more diagnoses, were comorbid, had more surgical procedures, complications perioperatively, infection, concussion and urinary tract infection. For hospitals, this can help raise awareness and lead to better management of specific diagnoses in order to avoid monetary deficits. For the public health sector, this information may be considered in future revisions of the DRG.
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http://dx.doi.org/10.4414/smw.2018.14650DOI Listing
August 2018

Heart rate elevations during early sepsis predict death in fluid-resuscitated rats with fecal peritonitis.

Intensive Care Med Exp 2018 Aug 20;6(1):28. Epub 2018 Aug 20.

Institute of Anesthesiology, University and University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.

Background: In sepsis, early outcome prediction would allow investigation of both adaptive mechanisms underlying survival and maladaptive mechanisms resulting in death. The aim of this study was to test whether early changes in heart rate monitored by telemetry could predict outcome in a long-term rat model of fecal peritonitis.

Methods: Male Wistar rats (n = 24) were instrumented with a central venous line for administration of fluids, antibiotics and analgesics. A telemetry transmitter continuously collected electrocardiogram signals. Sepsis was induced by intraperitoneal injection of fecal slurry, and the animals were observed for 48 h. Additional animals underwent arterial cannulation at baseline (n = 9), 4 h (n = 16), or 24 h (n = 6) for physiology and laboratory measurements.

Results: 48-h mortality was 33% (8/24), with all deaths occurring between 4 and 22 h. Septic animals were characterized by lethargy, fever, tachycardia, positive blood cultures, and elevated cytokine (IL-1, IL-6, TNF alpha) levels. An increase in heart rate ≥ 50 bpm during the first 4 h of sepsis predicted death with sensitivity and specificity of 88% (p = 0.001).

Conclusions: In this long-term rat sepsis model, prognostication could be made early by telemetry-monitored changes in heart rate. This model enables the study of underlying mechanisms and the assessment of any differential effects of novel therapies in predicted survivors or non-survivors.
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http://dx.doi.org/10.1186/s40635-018-0190-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102166PMC
August 2018

Efficacy of selective digestive decontamination in patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell transplantation.

Leuk Lymphoma 2019 03 21;60(3):685-695. Epub 2018 Aug 21.

a Center for Hematology and Oncology, University Hospital Zurich , Switzerland.

Selective digestive decontamination (SDD) with the oral, non-absorbable antimicrobial substances gentamicin, vancomycin and amphotericin B was optionally used at our institution to reduce the risk of gastrointestinal tract derived infections in multiple myeloma (MM) patients undergoing high-dose chemotherapy with subsequent autologous stem cell transplantation (HDCT/ASCT). The majority of patients received sulfamethoxazole-trimethoprim as pneumocystis pneumonia prophylaxis. From 203 patients receiving their first HDCT/ASCT between 2009 and 2015, we compared retrospectively 90 patients receiving SDD to 113 patients not receiving SDD. The administration of SDD was associated with a reduction of bacterial infections after HDCT/ASCT (overall: 8% versus 24%, p = .002; gram-negative pathogens: 1% versus 11%, p = .006) and less use of systemic antibiotics (62% versus 77%, p = .022). Omission of SDD was an independent risk factor for developing neutropenic fever and bloodstream infections. SDD could be an option to reduce bacterial infections in patients undergoing HDCT/ASCT that needs to be tested in prospective trials.
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http://dx.doi.org/10.1080/10428194.2018.1496332DOI Listing
March 2019

Long-Term Prognosis of Patients With Takotsubo Syndrome.

J Am Coll Cardiol 2018 08;72(8):874-882

Deutsches Herzzentrum München, Technische Universität München, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.

Background: Prognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive.

Objectives: This study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers.

Methods: Patients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions.

Results: Overall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients.

Conclusions: Overall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621).
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http://dx.doi.org/10.1016/j.jacc.2018.06.016DOI Listing
August 2018

Correlation between increased orbital volume and enophthalmos and diplopia in patients with fractures of the orbital floor or the medial orbital wall.

J Craniomaxillofac Surg 2018 Sep 13;46(9):1544-1549. Epub 2018 Jun 13.

Department of Oral and Maxillofacial Surgery, University Hospital of Zürich, (Head of Department: Prof. Dr. med. Dr. med. dent. Martin Rücker), Frauenklinikstrasse 24, 8091, Zürich, Switzerland. Electronic address:

Fractures of the orbital floor and medial orbital wall (blowout fractures) are common midface injuries. Diagnostic methods and treatment options have improved over recent years, due to threedimensional image processing and the use of patient-specific implants. Nonetheless, the indications for orbital reconstructive surgery are still controversial. Previous authors have reported a linear correlation between post-traumatic increases in orbital volume and enophthalmos and diplopia. Post-traumatic increases in orbital volume are often considered to be predictive of long-term symptoms; therefore, it is commonly recommended that orbital volume increases be treated as an indication for early reconstructive surgery. However, the results of this study did not show any statistically significant long-term linear correlation between increased orbital volume and enophthalmos or diplopia, and the performance of orbital volume as a predictor of ocular symptoms was poor. Hence, we do not consider increased post-traumatic orbital volume to be particularly useful for predicting late enophthalmos or diplopia. However, a statistical correlation between fractures of the anterior and medial thirds of the orbital floor and double vision was found. As such, fractures of the middle and anterior third should be regarded as problematic, and surgical reconstruction should be considered in these cases.
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http://dx.doi.org/10.1016/j.jcms.2018.06.008DOI Listing
September 2018

A Prospective Analysis of the Effects of Nerve-Sparing Radical Prostatectomy on Urinary Continence Based on Expanded Prostate Cancer Index Composite and International Index of Erectile Function Scoring Systems.

Int Neurourol J 2018 Jun 30;22(2):123-132. Epub 2018 Jun 30.

Division of Urology, Department of Surgery, Kantonsspital Baden, Baden, Switzerland.

Purpose: This study aims to objectively characterize the effect of successful nerve sparing (NS) during radical prostatectomy (RP) on postoperative urinary continence (UC) using International Index of Erectile Function (IIEF)-scores and a previously described Expanded Prostate Cancer Index Composite (EPIC) score cutoff value (COV) for UC. Several notable studies on this topic present conflicting outcomes. This is largely due to a lack of clear definitions and consensus regarding preserved erectile function (EF) and UC.

Methods: This study is comprised of all patients who underwent RP at the Kantonsspital Baden, Switzerland, between 2004 and 2013. Patients completed self-assessment questionnaires for UC (EPIC) and EF (IIEF) pre- and postoperatively (3, 6, 9, 12, 18, and 24 months; yearly thereafter). We used a previously described EPIC subscore COV, with "satisfactory continence" signified by a score >85. Statistical analysis was performed using Kaplan-Meier and Cox regression analyses for "surgeon-" and "IIEF-defined" NS definitions.

Results: Of 236 men with a median age of 63 years (interquartile range [IQR], 59-66 years) and median follow-up time of 48 months (IQR, 30-78 months), 176 underwent unilateral (n=33) or bilateral (n=143) NS RP. Fifty-four underwent non-NS (NNS) RP. Kaplan-Meier analyses identified the following risk factors for UC: age, prostate volume, cancer risk group, and NS status. In surgeon-defined NS RP cases, multivariate analysis for regaining continence demonstrated no significant difference (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.48-1.25; P=0.3). With successful IIEF-defined NS RPs, regression analysis demonstrated no significant difference (HR, 0.89; 95% CI, 0.59-1.35; P=0.58).

Conclusions: In our population, analysis and comparison of surgeon- and IIEF-defined NS and NNS cohorts revealed that NS RP did not improve postoperative UC. The conservation of UC alone should not motivate surgeons or patients to pursue NS RP.
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http://dx.doi.org/10.5213/inj.1836052.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059911PMC
June 2018

Do surgical modifications at the annular level during the Ross procedure negatively influence the structural and functional durability of the autograft?

Interact Cardiovasc Thorac Surg 2018 11;27(5):642-649

Department of Surgery for Congenital Heart Defects, Pediatric Heart Center Duisburg, University of Düsseldorf, Duisburg, Germany.

Objectives: Do surgical modifications at the annular level (e.g. the modified Ross-Konno procedure or reduction plasty) influence the structure and function of the Ross autograft at the mid-term follow-up?

Methods: From June 2001 to July 2009, 49 patients (37 men and 12 women), mean age 10.5 ± 5.7 years (range 2 weeks to 17.8 years), underwent Ross operations. Twenty-one patients underwent additional aortic annulus reduction plasty and 9 patients a modified Ross-Konno procedure. The need for reintervention, reoperation and valve function were retrospectively analysed for a mean follow-up of 4.6 ± 2.7 years (range 9 days to 9.2 years).

Results: There were no intraoperative or early death. Three late deaths occurred. Survival at 4 years was 91.9 ± 4.6%. In the overall cohort, aortic annular growth was 1 mm/year, corresponding to a z-score increase of 0.24/year (no mismatch group), 0.21/year (reduction plasty group) and 0.34/year (Ross-Konno group). At the last follow-up, sinotubular junction z-scores were 2.8 ± 1, 3 ± 1 and 2.4 ± 0.9 in the no mismatch, reduction plasty, and Ross-Konno groups, respectively. Ninety-three percent of patients presented with none-to-mild autograft valve regurgitation. The Ross-Konno group showed a significant increase in aortic annulus size (z-score of the annulus at the last follow-up 3.6 ± 1.6; P = 0.036). The no mismatch and the reduction plasty groups showed z-scores within the normal range (2.1 ± 1.7 and 2.5 ± 1.6, respectively).

Conclusions: Additional aortic annulus reduction or enlargement does not disturb the structural and functional durability of the autograft at the mid-term follow-up. Long-term autograft integrity, especially in the Ross-Konno group, remains to be investigated.
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http://dx.doi.org/10.1093/icvts/ivy135DOI Listing
November 2018