Performance of Transcatheter Direct Annuloplasty in Patients With Atrial and Nonatrial Functional Tricuspid Regurgitation.

BACKGROUND: A novel echocardiography-based definition of atrial functional tricuspid regurgitation (A-FTR) has shown superior outcomes in patients undergoing conservative treatment or tricuspid valve transcatheter edge-to-edge repair. Its prognostic significance for transcatheter tricuspid valve annuloplasty (TTVA) outcomes is unknown. OBJECTIVES: This study sought to investigate prognostic, clinical, and technical implications of A-FTR phenotype in patients undergoing TTVA. METHODS: This multicenter study investigated clinical and echocardiographic outcomes up to 1 year in 165 consecutive patients who underwent TTVA for A-FTR (characterized by the absence of tricuspid valve tenting, midventricular right ventricular [RV] dilatation, and impaired left ventricular ejection fraction) and nonatrial functional tricuspid regurgitation (NA-FTR). RESULTS: A total of 62 A-FTR and 103 NA-FTR patients were identified, with the latter exhibiting more pronounced RV remodeling. Compared to baseline, the tricuspid regurgitation (TR) grade at discharge was significantly reduced (P < 0.001 for both subtypes), and TR ≤II was achieved more frequently in A-FTR (85.2% vs 60.8%; P = 0.001). Baseline TR grade and A-FTR phenotype were independently associated with TR ≤II at discharge and 30 days. In multivariate analyses, A-FTR phenotype was a strong predictor (OR: 5.8; 95% CI: 2.1-16.1; P < 0.001) of TR ≤II at 30 days. At 1 year, functional class had significantly improved compared to baseline (both P < 0.001). One-year mortality was lower in A-FTR (6.5% vs 23.8%; P = 0.011) without significant differences in heart failure hospitalizations (13.3% vs 22.7%; P = 0.188). CONCLUSIONS: Direct TTVA effectively reduces TR in both A-FTR, which is a strong and independent predictor of achieving TR ≤II, and NA-FTR. Even though NA-FTR showed more RV remodeling at baseline, both phenotypes experienced similar symptomatic improvement, emphasizing the benefit of TTVA even in advanced disease stages. Additionally, phenotyping was of prognostic relevance in patients undergoing TTVA.

Eight weeks of exercise intervention improves visuomotor and functional capacity, performance, and physiological profile in a patient with choroidal melanoma.

The aim of this case study was to investigate the effects of an 8-wk combined exercise intervention, consisting of visual-coordinative and high-intensity interval training (HIIT), on the physical and visuomotor-functional capacity, performance, and physiological profile of a moderately active 29-yr-old man diagnosed with choroidal melanoma of the left eye. Data were collected on three occasions: at the initial diagnosis (T0), after hospitalization and radiotherapy treatment (T1), and following the recovery through the exercise intervention (T2), spanning a total of 17 wk. The primary outcome variables consisted of visuomotor and functional tests (VFTs), cardiorespiratory fitness (CRF), and microvascular circulation measured via flicker light-induced dilation (FiD). For visuomotor tests in general, a significant decline was observed between baseline T0 and T1 (by 6%-22%), followed by significant improvements at T2 (by 11%-36%), surpassing the initially observed T0 values. The cardiopulmonary exercise testing (CPET)-derived parameters exhibited a similar pattern, declining from T0 to T1 [by 8%-12% for peak V̇o2, peak power output (PO), and CPET duration, respectively], with a subsequent recovery observed in response to 8 wk of exercise training (T2), resulting in increases of 11%-25% for V̇o2, peak PO, and CPET duration. Interestingly, the dilation of both arteries and veins in response to the FiD stimulus exhibited a twofold increase compared with baseline levels. Our results suggest that the 8-wk exercise intervention improved patients' VFT and CRF profiles and exceeded baseline values. Additional investigation, particularly through randomized controlled trials, is needed to comprehensively explain changes in FiD.NEW & NOTEWORTHY Results presented here suggest that combined visual-coordinative and HIIT training improves the visual-functional capacity, performance, and physiological profile of choroidal melanoma patients during treatment recovery. This case study lays the groundwork for further research concerning exercise therapy in this unique patient population. In addition, further investigation is required to fully comprehend the combined effects of exercise and radiation therapy on vasculature and oxygenation in patients with choroidal melanoma.

Optic Nerve Sheath Diameter for Assessing Prognosis after Out-of-Hospital Cardiac Arrest.

PURPOSE: Evaluate optic nerve sheath and pial diameters (ONSD, ONPD) via sonography and computed tomography (CT) after out-of-hospital cardiac arrest (CA) and to compare their prognostic significance with other imaging and laboratory biomarkers. MATERIALS AND METHODS: A prospective observational study enrolling patients after successful resuscitation between December 2017 and August 2021. ONSD and ONPD were measured with sonography. Additionally, ONSD, and also grey-to-white ratio at basal ganglia (GWRBG) and cerebrum (GWRCBR), were assessed using CT. Lactate and neuron specific enolase (NSE) blood levels were measured. RESULTS: Sonographically measured ONSD and ONPD yielded no significant difference between survival and non-survival (p values ≥0.4). Meanwhile, CT assessed ONSD, GWRBG, GWRCBR, and NSE levels significantly differed regarding both, survival (p values ≤0.005) and neurological outcome groups (p values ≤0.04). For survival prognosis, GWRBG, GWRCBR, and NSE levels appeared as excellent predictors; in predicting a good neurological outcome, NSE had the highest accuracy. CONCLUSIONS: CT diagnostics, in particular GWRBG and GWRCBR, as well as NSE as laboratory biomarker, appear as excellent outcome predictors. Meanwhile, our data lead us to recommend caution in utilizing sonography assessed ONSD and ONPD for prognostic decision-making post-CA.

One-Year Outcomes According to Mitral Regurgitation Etiology Following Transcatheter Edge-to-Edge Repair With the PASCAL System: Results From a Multicenter Registry.

BACKGROUND: We previously reported procedural and 30-day outcomes of a German early multicenter experience with the PASCAL system for severe mitral regurgitation (MR). This study reports 1-year outcomes of mitral valve transcatheter edge-to-edge repair with the PASCAL system according to MR etiology in a large all-comer cohort. METHODS AND RESULTS: Clinical and echocardiographic outcomes up to 1-year were investigated according to MR etiology (degenerative [DMR], functional [FMR], or mixed [MMR]) in the first 282 patients with symptomatic MR 3+/4+ treated with the PASCAL implant at 9 centers in 2019. A total of 282 patients were included (33% DMR, 50% FMR, 17% MMR). At discharge, MR reduction to ≤1+/2+ was achieved in 58%/87% of DMR, in 75%/97% of FMR, and in 78%/98% of patients with MMR (P=0.004). MR reduction to ≤1+/2+ was sustained at 30 days (50%/83% DMR, 67%/97% FMR, 74%/100% MMR) and at 1 year (53%/78% DMR, 75%/97% FMR, 67%/91% MMR) with significant differences between etiologies. DMR patients with residual MR 3+/4+ at 1-year had at least complex valve morphology in 91.7%. Valve-related reintervention was performed in 7.4% DMR, 0.7% FMR, and 0.0% MMR (P=0.010). At 1-year, New York Heart Association Functional Class was significantly improved irrespective of MR etiology (P<0.001). CONCLUSIONS: In this large all-comer cohort, mitral valve transcatheter edge-to-edge repair with the PASCAL system was associated with an acute and sustained MR reduction at 1-year in all causes. However, in patients with DMR, MR reduction was less pronounced, reflecting the high incidence of complex or very complex anatomies being referred for mitral valve transcatheter edge-to-edge repair.

Early in-hospital discontinuation of aspirin on the first post-procedural day after percutaneous coronary stent implantation in patients on direct oral anticoagulation.

Background: Previous trials investigating antithrombotic therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor after percutaneous coronary intervention (PCI), termed dual therapy, allowed a short period of triple therapy including a DOAC, a P2Y12 inhibitor, and aspirin. Aims: This study aimed to determine whether discontinuation of aspirin on the first post-procedural day is safe or causes ischemic events. Methods: Ischemic and bleeding events during hospitalization were investigated retrospectively in all patients treated with dual therapy (DOAC + P2Y12 inhibitor, designated as group 1) or triple therapy (DOAC + P2Y12 inhibitor+aspirin, designated as group 2) from day 1 after PCI at our center. Results: Of 4,564 consecutive PCI procedures, 1,059 (23.2%) had an indication for OAC. Of these, 322 met the inclusion criteria for group 1 and 62 for group 2. Baseline characteristics, CHA2DS2-VASc and HAS-BLED scores showed no relevant differences between the two groups, and the main indication for DOAC therapy was atrial fibrillation in both groups. Approximately » of patients were treated for acute coronary syndrome. The mean length of post-procedural hospitalization was 2.1 ± 2.5 and 2.2 ± 3.0 days in group 1 and 2, respectively (p = 0.305). One patient per group suffered a TIA (p = 0.297). There were no other ischemic events and no statistically significant differences in bleeding events. A subgroup analysis of cases hospitalized for ≥2 post-procedural days (group 1: 100 cases, mean 4.4 ± 3.4 days vs. group 2: 25 cases, mean 4.0 ± 4.1 days) confirmed these results. Conclusion: The initiation of dual therapy and thus discontinuation of aspirin on the first postprocedural day appears to be safe with respect to short-term ischemic events in a real-world population. Almost » of patients undergoing PCI have an indication for OAC, highlighting the relevance of this issue.

Vascular Ultrasound for In Vivo Assessment of Arterial Pathologies in a Murine Model of Atherosclerosis and Aortic Aneurysm.

Vascular diseases like atherosclerosis and abdominal aortic aneurysm (AAA) are common pathologies in the western world, promoting various potentially fatal conditions. Here, we evaluate high-resolution (HR) ultrasound in mouse models of atherosclerosis and AAA as a useful tool for noninvasive monitoring of early vascular changes in vivo. We used Apolipoprotein E-deficient (ApoE-/-) mice as an atherosclerosis model and induced AAA development by the implementation of Angiotensin II-releasing osmotic minipumps. HR ultrasound of the carotid artery or the abdominal aorta was performed to monitor vascular remodeling in vivo. Images were analyzed by speckle tracking algorithms and correlated to histological analyses and subsequent automated collagen quantification. Consistent changes were observed via ultrasound in both models: Global radial strain (GRS) was notably reduced in the AAA model (23.8 ± 2.8% vs. 12.5 ± 2.5%, p = 0.01) and in the atherosclerotic mice (20.6 ± 1.3% vs. 15.8 ± 0.9%, p = 0.02). In mice with AAA, vessel distensibility was significantly reduced, whereas intima-media thickness was increased in atherosclerotic mice. The area and collagen content of the tunica media were increased in diseased arteries of both models as measured by automated image analysis of Picrosirius Red-stained aortic sections. Correlation analysis revealed a strong correlation of multiple parameters, predicting early vascular damage in HR ultrasound and histological examinations. In conclusion, our findings underscore the potential of HR ultrasound in effectively tracing early alterations in arterial wall properties in murine models of atherosclerosis and AAA.

Thoracic aorta diameters in Marfan patients: Intraindividual comparison of 3D modified relaxation-enhanced angiography without contrast and triggering (REACT) with transthoracic echocardiography.

OBJECTIVE: To compare the measurement of aortic diameters using a novel flow-independent MR-Angiography (3D modified Relaxation-Enhanced Angiography without Contrast and Triggering (modified REACT)) and transthoracic echocardiography (TTE) in Marfan syndrome (MFS) patients. MATERIAL AND METHODS: This retrospective, single-center analysis included 46 examinations of 32 MFS patients (mean age 37.5 ± 11.3 years, 17 women, no prior aortic surgery) who received TTE and 3D modified REACT (ECG- and respiratory-triggering, Compressed SENSE factor 9 for acceleration of image acquisition) of the thoracic aorta. Aortic diameters (sinus of Valsalva (SV), sinotubular junction (STJ), and ascending aorta (AoA)) were independently measured by two cardiologists in TTE (leading-edge) and two radiologists in modified REACT (inner-edge, using multiplanar reconstruction). Intraclass correlation coefficient, Bland-Altman analyses, and Pearson's correlation (r) were used to assess agreement between observers and methods. RESULTS: Interobserver correlation at the SV, STJ, and AoA were excellent for both, TTE (ICC = 0.95-0.98) and modified REACT (ICC = 0.99-1.00). There was no significant difference between TTE and modified REACT for diameters measured at the SV (39.24 ± 3.24 mm vs. 39.63 ± 3.76 mm; p = 0.26; r = 0.78) and the STJ (35.16 ± 4.47 mm vs. 35.37 ± 4.74 mm; p = 0.552; r = 0.87). AoA diameters determined by TTE were larger than in modified REACT (34.29 ± 5.31 mm vs. 30.65 ± 5.64 mm; p < 0.01; r = 0.74). The mean scan time of modified REACT was 05:06 min ± 02:47 min, depending on the patient's breathing frequency and heart rate. CONCLUSIONS: Both TTE and modified REACT showed a strong correlation for all aortic levels; however, at the AoA, diameters were larger using TTE, mostly due to the limited field of view of the latter with measurements being closer to the aortic valve. Given the excellent interobserver correlation and the strong agreement with TTE, modified REACT represents an attractive method to depict the thoracic aorta in MFS patients.

How to... train your skills goes digital! A project report on the development and implementation of practice-oriented digital student tutorials.

Objective: This project report outlines the development and implementation of digital tutorials ("How to... train your skills goes digital!") by peer tutors (TUTs) based on previously established in-person tutorials, as well as the subsequent combination of both approaches. The TUTs' objective, in spite of corona-related restrictions and strict hygiene requirements during the pandemic, was to provide fellow students with the opportunity to learn, practice and reflect on clinical-practical skills. Methodology: In a collaborative undertaking, the TUTs first analyzed the learning objectives of the in-person tutorials in order to be able to design content-matched digital tutorials without entirely abandoning the practical aspect. The Moodle learning management platform was selected as the appropriate tool for delivery of the relevant theoretical knowledge. Practical exercises are embedded in the digital tutorials during online meetings. The participants (PTs) create their own models in the sense of a home skills station based on instructions provided via Moodle. Acceptance was systematically documented via questionnaires. Results: The digital tutorials were well accepted by the PTs (n=64). Evaluation (response rate: 37.5%) outcomes were consistently positive. Both course implementation and the PTs' own progress were rated "good" to "very good". Nevertheless, the PTs do not yet feel well-prepared to carry out the various activities practiced independently. In the winter semester of 2020/21, the in-person tutorials were also reintroduced in a combined format. The marked demand for the tutorials may indicate the PT preference for practice on the simulation center models. Conclusion: The systematic combination of digital and in-person tutorials using the flipped classroom approach would appear to make sense in the long run. The effectiveness and sustainability of this approach in comparison with in-person tutorials only should be further investigated.

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

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.

Protective Effects of Therapeutic Neutrophil Depletion and Myeloperoxidase Inhibition on Left Ventricular Function and Remodeling in Myocardial Infarction.

Myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Improved survival has led to an increasing incidence of ischemic cardiomyopathy, making it a major reason for hospitalization in the western world. The inflammatory response in the ischemic myocardium determines the extent of structural remodeling and functional deterioration, with neutrophils (PMN) being a key modulator of the propagation and resolution of inflammation. The heme enzyme myeloperoxidase (MPO) is abundantly expressed in PMN and is an important mediator of their inflammatory capacities. Here, we examine the effects of PMN reduction, MPO deficiency and MPO inhibition in two murine models of MI. Reduction in PMN count resulted in less scar formation and improved cardiac function. Similar results were obtained in genetically MPO deficient mice, suggesting that MPO is a critical factor in PMN-mediated cardiac remodeling. To test our findings in a therapeutic approach, we orally administered the MPO inhibitor AZM198 in the context of MI and could demonstrate improved cardiac function and reduced structural remodeling. Therefore, MPO appears to be a favorable pharmacological target for the prevention of long-term morbidity after MI.

Hydroxylamine-mediated C-C amination via an aza-hock rearrangement.

Despite the widespread use of anilines, synthetic challenges to these targets still exist. Selectivity is often an issue, when using the traditional nitration-reduction sequence or more modern approaches, including arene C-H aminations catalyzed by transition metals, photosensitizers, or electrodes. Accordingly, there is still a need for general methods to rapidly, directly access specific isomers of substituted anilines. Here, we report a simple route towards the synthesis of such motifs starting from benzyl alcohols, which are converted to anilines by the use of arylsulfonyl hydroxylamines, via an aza-Hock rearrangement. Good to excellent yields are observed. The method is applicable to various benzyl alcohol surrogates (such as ethers, esters, and halides) as well as simple alkylarenes. Functionalizations of pharmaceutically relevant structures are feasible under the reaction conditions. Over ten amination reagents can be used, which facilitates the rapid assembly of a vast set of compounds.

Expanded Ring NHC Silver Carboxylate Complexes as Efficient and Reusable Catalysts for the Carboxylative Cyclization of Unsubstituted Propargylic Derivatives.

Stabilized by a bulky N-heterocyclic carbene [BP DPr, 1,3-bis(2,6-diisopropylphenyl)-1,3-diazonine-2-ylidene] ligand, new silver carboxylate complexes of the form BP DPrAgO2 C-R (R=Me, Ph) have been synthesized and fully characterized in solution and in the solid state and implemented as sole catalysts (base-, additive-, and, in some cases, solvent-free) in the challenging fixation of carbon dioxide to unsubstituted propargylic derivatives for the synthesis of oxazolidinones and α-methylene cyclic carbonates. Derived from X-ray diffraction studies, the molecular geometry and the concept of buried volume were employed to describe the structural and steric features of these silver complexes. Their stability and efficiency as catalysts have been demonstrated by the synthesis of 29 carboxylation products (72-98 % yield) at low catalyst loadings (0.01-1.5 mol%). Characteristics are high turnover numbers (up to 9400), catalyst recyclability (up to 96 % yield after the 7th cycle with no decomposition of the silver complex), and the possibility to scale-up the reaction.

Retained placenta and postpartum hemorrhage: time is not everything.

PURPOSE: Postpartum hemorrhage is the major cause of maternal mortality worldwide. Retained placenta accounts for nearly 20% of severe cases. We investigated the influence of the time factor and retained placenta etiology on postpartum hemorrhage dynamics. METHODS: Our retrospective study analyzed a single-center cohort of 296 women with retained placenta. Blood loss was measured using a validated and accurate technique based on calibrated blood collection bags, backed by the post- vs pre-partum decrease in hemoglobin. We evaluated the relationship between these two blood loss parameters and the duration of the third stage of labor using Spearman rank correlation, followed by subgroup analysis stratified by third stage duration and retained placenta etiology. RESULTS: Correlation analysis revealed no association between third stage duration and measured blood loss or decrease in hemoglobin. A shorter third stage (< 60 min) was associated with significantly increased uterine atony (p = 0.001) and need for blood transfusion (p = 0.006). Uterine atony was significantly associated with greater decrease in hemoglobin (p < 0.001), higher measured blood loss (p < 0.001), postpartum hemorrhage (p = 0.048), and need for blood transfusion (p < 0.001). CONCLUSION: Postpartum blood loss does not correlate with third stage duration in women with retained placenta. Our results suggest that there is neither a safe time window preceding postpartum hemorrhage, nor justification for an early cut-off for manual removal of the placenta. The prompt detection of uterine atony and immediate prerequisites for manual removal of the placenta are key factors in the management of postpartum hemorrhage.

Screening for iron deficiency in surgical patients based on noninvasive zinc protoporphyrin measurements.

BACKGROUND: Approximately every third surgical patient is anemic. The most common form, iron deficiency anemia, results from persisting iron-deficient erythropoiesis (IDE). Zinc protoporphyrin (ZnPP) is a promising parameter for diagnosing IDE, hitherto requiring blood drawing and laboratory workup. STUDY DESIGN AND METHODS: Noninvasive ZnPP (ZnPP-NI) measurements are compared to ZnPP reference determination of the ZnPP/heme ratio by high-performance liquid chromatography (ZnPP-HPLC) and the analytical performance in detecting IDE is evaluated against traditional iron status parameters (ferritin, transferrin saturation [TSAT], soluble transferrin receptor-ferritin index [sTfR-F], soluble transferrin receptor [sTfR]), likewise measured in blood. The study was conducted at the University Hospitals of Frankfurt and Zurich. RESULTS: Limits of agreement between ZnPP-NI and ZnPP-HPLC measurements for 584 cardiac and noncardiac surgical patients equaled 19.7 µmol/mol heme (95% confidence interval, 18.0-21.3; acceptance criteria, 23.2 µmol/mol heme; absolute bias, 0 µmol/mol heme). Analytical performance for detecting IDE (inferred from area under the curve receiver operating characteristics) of parameters measured in blood was: ZnPP-HPLC (0.95), sTfR (0.92), sTfR-F (0.89), TSAT (0.87), and ferritin (0.67). Noninvasively measured ZnPP-NI yielded results of 0.90. CONCLUSION: ZnPP-NI appears well suited for an initial IDE screening, informing on the state of erythropoiesis at the point of care without blood drawing and laboratory analysis. Comparison with a multiparameter IDE test revealed that ZnPP-NI values of 40 µmol/mol heme or less allows exclusion of IDE, whereas for 65 µmol/mol heme or greater, IDE is very likely if other causes of increased values are excluded. In these cases (77% of our patients) ZnPP-NI may suffice for a diagnosis, while values in between require analyses of additional iron status parameters.

Clinical practice of pre-hospital analgesia: An observational study of 20,978 missions in Switzerland.

BACKGROUND: Pain is a frequent problem faced by emergency medical services (EMS) in pre-hospital settings. This large observational study aims to assess the prevalence of sufficiently provided analgesia and to analyze the efficacy of different analgesics. Moreover, we evaluated if quality of analgesia changed with an emergency physician on scene or depended on paramedics' gender. METHODS: This is a retrospective analysis of all pre-hospital medical charts from adults and adolescents treated by the municipal EMS Schutz & Rettung Zürich over a period of 4 years from 2013 to 2016. Inclusion criteria were age ≥16 years, initial GCS > 13, NACA score ≥I and ≤V, an initial numeric rating scale (NRS) ≥ I and a documented NRS at hospital admission. 20,978 out of 142,484 missions fulfilled the inclusion criteria and therefore underwent further investigation. Descriptive, univariate and multivariate analyses were applied. RESULTS: Initial NRS on scene was on average 5.2 ± 3.0. Mean NRS reduction after treatment was 2.2 ± 2.5 leading to a NRS at hospital admission of 3.0 ± 1.9. This resulted in sufficient analgesia for 77% of included patients. Among analgesics, the highest odds ratio for sufficient analgesia was observed for ketamine (OR 4.7, 95%CI 2.2-10.4, p < 0.001) followed by fentanyl (OR 1.4, 95%CI 1.1-1.7, p = 0.004). Female paramedics provided better analgesia (OR 1.2, 95%CI 1.1-1.2; p < 0.001). Patient's sex had no influence on analgesia. In patients with a NACA score > 2, the presence of an emergency physician on scene improved the quality of analgesia significantly. CONCLUSIONS: Pre-hospital analgesia is mostly adequate, especially when done with ketamine or fentanyl. Female paramedics provided better analgesia and in selected patients, an emergency physician on scene improved quality of analgesia in critical patients.

Impact of rivaroxaban plasma concentration on perioperative red blood cell loss.

BACKGROUND: This study investigates the impact of preoperative calculated rivaroxaban (RXA) plasma concentration on perioperative red blood cell (RBC) loss. STUDY DESIGN AND METHODS: In this retrospective single-center study, we identified patients with RXA intake according to a preoperative determination of RXA levels within 96 hours before surgery. RXA plasma concentration at the beginning of surgery was then calculated from the last RXA intake using a single-compartment pharmacokinetic model with four categories of RXA concentration (≤20, 21-50, 51-100, and >100 µg/L). Patients were classified into surgery with high (≥500 mL) or low (<500 mL) expected blood loss. Perioperative bleeding was determined by calculating RBC loss. RESULTS: We analyzed 308 surgical interventions in 298 patients during the period from January 2012 to July 2018. Among patients undergoing surgery with low expected blood loss, RBC loss varied from 164 mL (standard deviation [SD], 189) to 302 mL (SD, 397) (p = 0.66), and no association of calculated RXA concentration with RBC loss was observed. In patients undergoing surgery with high expected blood loss, we found a significant correlation of calculated RXA concentration with RBC loss (Pearson's correlation coefficient, 0.29; p = 0.002). RBC loss increased with rising RXA concentration from 575 mL (SD, 365) at RXA concentration of 20 µg/L or less up to 1400 mL (SD, 1300) at RXA concentration greater than 100 µg/L. RXA concentration greater than 100 µg/L was associated with a significant increase of in RBC loss of 840 mL (95% confidence interval, 360-1300; p < 0.001). Transfusion of RBC and fresh frozen plasma units tended to increase in patients with RXA concentrations greater than 100 µg/L. The proportion of patients treated with prothrombin complex concentrate and coagulation factor XIII concentrate increased significantly with higher RXA concentrations. CONCLUSION: Only in surgery with high expected blood loss, a calculated RXA concentration of greater than 100 µg/L was associated with a significant increase of perioperative RBC loss.

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

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; p < 0.001), INR (Pearson's correlation coefficient 0.5; p < 0.001), and aPTT (Pearson's correlation coefficient 0.53; p < 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.

Outcome, quality of life and direct costs after out-of-hospital cardiac arrest in an urban region of Switzerland.

BACKGROUND: Considering the significant morbidity and mortality of out-of-hospital cardiac arrest, only little data on survival or quality of life after successful resuscitation is available in Europe. Additionally, economic aspects of such events are poorly studied. The purpose of this study is to provide data for survival, quality of life and costs directly related to the cardiac arrest for a region of Switzerland served by one emergency medical service (EMS). METHODS: Eighty eight patients older than 18 years of age that were resuscitated by the EMS Winterthur in the year 2013 were included and retrospective analysis of EMS-protocols was performed. For patients alive at follow-up, 2 years after the event, a structured interview with quality of life questionnaires was conducted. This study was accepted by the local Ethics Committee. RESULTS: Thirty five percent (n = 31) of resuscitated patients were admitted alive to the hospital following out-of-hospital cardiac arrest. This incidence was as high as 60%, if the patients had a shockable rhythm as first rhythm. Survival to follow-up was 16% (n = 14). These patients had an excellent quality of life overall, with little to no limitations in daily life. There was no significant difference in survival for patients in outlying regions with comparatively longer timespans until arrival of EMS. Median EMS-costs for deceased patients were CHF 1731 (inter-quartile range 346), for survivors CHF 2'169 (inter-quartile range CHF 444) and median hospital-costs were CHF 27'707 (inter-quartile range CHF 62'783). CONCLUSION: Quality of care for patients with out-of-hospital cardiac arrest in the region of Winterthur is high, including patients in outlying regions. The associated costs are similar to other European countries. TRIAL REGISTRATION: This trial was registered with www.clinicaltrials.gov under NCT02625883.

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

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.