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Background Data on the influence of age and body mass index (BMI) on energy metabolism of the critically ill are heterogeneous. Due to the increasingly aging critically ill population, investigation on age- and BMI-specific energy metabolism is relevant. Methods A total of 394 indirect calorimetry measurements were conducted on 348 critically ill adult medical patients, including 46 repeat measurements after 3.6 [plus or minus] 4.3 days. Measured resting energy expenditure (MREE) was compared for age groups, BMI, and gender. Predicted energy expenditure (PEE) using the Penn State, Swinamer, and Ireton-Jones equations and the ACCP recommendations was also compared with MREE. Results The patients were 65.6 [plus or minus] 14.5 years old. Their mean Acute Physiology and Chronic Health Evaluation II score was 27.6 [plus or minus] 7.8. Mean BMI was 27.8 [plus or minus] 8.4 kg/m.sup.2, and 25.6% were obese. MREE adjusted for ideal body weight decreased with increasing age, while it increased with increasing BMI. Age, BMI, and gender are independent determinants of MREE after adjusting for clinical factors (R.sup.2 = 0.34). All four prediction equations showed a proportional bias, with the Penn State equation performing acceptably. In 46 patients with repeat indirect calorimetry, there was no significant difference between the first and second MREE (p = 0.62). Conclusions Age, BMI, and gender are independent determinants of resting energy expenditure in critically ill adults. Variations between measured and predicted energy expenditure are considerable. Should prediction equations be used, their performance in the specific population should be taken into consideration. Repeat indirect calorimetry may not always be necessary. However, this may depend on the length of stay and the extent of stress., Author(s): Christin Hölzel [sup.1] , Lorenz Weidhase [sup.1] , Sirak Petros [sup.1] Author Affiliations: (1) Medical ICU, University Hospital Leipzig, Leipzig, Germany Introduction Defining the optimal energy requirement of the [...]

Introduction: Recombinant porcine factor VIII (rpFVIII) is a treatment option for break‐through bleeds in patients with congenital haemophilia A with inhibitors (CHAwI) on emicizumab. However, there are limited data about the measurement of rpFVIII in the presence of emicizumab. Aim: To analyse whether rpFVIII can be measured with a chromogenic assay with bovine component (bCSA) in plasma from CHAwI on emicizumab treatment. Methods: In the first part of the study, FVIII deficient plasma was spiked with rpFVIII, in the second part, commercial plasma from CHAwI was spiked with emicizumab and rpFVIII, and in the third part, plasma from CHAwI on emicizumab treatment was spiked with rpFVIII. FVIII was then measured with bCSA and a chromogenic assay with human component (hCSA). Thrombin generation (TG) and clot‐waveform analysis (CWA) were also carried out. Results: The recovery of rpFVIII measured with bCSA is approximately 80% and is further influenced by the presence of an anti‐porcine inhibitor. rpFVIII assessed with hCSA was influenced by emicizumab. CWA and TG showed a weak correlation with baseline emicizumab concentration, but peak thrombin and CWA correlated well with increasing emicizumab concentrations and rpFVIII activities. Conclusion: This study indicates that rpFVIII can be measured in the presence of emicizumab with a bCSA. A calibration curve for the measurement of rpFVIII with bCSA should be established. [ABSTRACT FROM AUTHOR]

The article focuses on the dose-response relationship of direct oral anticoagulants (DOACs) at plasma levels below 100 nanograms (ng) per milliliter (mL). It describes a study that investigated the thrombin generation (TG) profiles of different DOACs at various plasma drug levels and highlights the non-linear dose-response relationship, with higher inhibition of thrombin generation observed at lower plasma levels.

Chest compressions during cardiopulmonary resuscitation (CPR) may be associated with iatrogenic chest wall injuries. The extent to which these CPR-associated chest wall injuries contribute to a delay in the respiratory recovery of cardiac arrest survivors has not been sufficiently explored. In a single-center retrospective cohort study, surviving intensive care unit (ICU) patients, who had undergone CPR due to medical reasons between 1 January 2018 and 30 June 2019, were analyzed regarding CPR-associated chest wall injuries, detected by chest radiography and computed tomography. Among 109 included patients, 38 (34.8%) presented with chest wall injuries, including 10 (9.2%) with flail chest. The multivariable logistic regression analysis identified flail chest to be independently associated with the need for tracheostomy (OR 15.5; 95% CI 2.77–86.27; p = 0.002). The linear regression analysis identified pneumonia (β 11.34; 95% CI 6.70–15.99; p < 0.001) and the presence of rib fractures (β 5.97; 95% CI 1.01–10.93; p = 0.019) to be associated with an increase in the length of ICU stay, whereas flail chest (β 10.45; 95% CI 3.57–17.33; p = 0.003) and pneumonia (β 6.12; 95% CI 0.94–11.31; p = 0.021) were associated with a prolonged duration of mechanical ventilation. Four patients with flail chest underwent surgical rib stabilization and were successfully weaned from the ventilator. The results of this study suggest that CPR-associated chest wall injuries, flail chest in particular, may impair the respiratory recovery of cardiac arrest survivors in the ICU. A multidisciplinary assessment may help to identify patients who could benefit from a surgical treatment approach. [ABSTRACT FROM AUTHOR]

Objectives: Patients with connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE) have an increased risk for infections. This study investigated the outcome and characteristics of CTD patients under intensive care unit (ICU) treatment for sepsis. Methods: A single-center retrospective analysis was conducted and reviewed all patients with a CTD diagnosis admitted to the ICU of a university hospital for sepsis between 2006 and 2019. Mortality was computed and multivariate logistic regression was used to detect independent risk factors for sepsis mortality. Furthermore, the positive predictive value of ICU scores such as Sequential Organ Failure Assessment (SOFA) score was evaluated. Results: This study included 44 patients with CTD (mean age 59.8 ± 16.1 years, 68.2% females), most of them with a diagnosed SLE (61.4%) followed by systemic sclerosis (15.9%). 56.8% (n = 25) were treated with immunosuppressives and 81.8% (n = 36) received glucocorticoids. Rituximab was used in 3 patients (6.8%). The hospital mortality of septic CTD patients was high with 40.9%. It was highest among systemic sclerosis (SSc) patients (85.7%). SOFA score and diagnosis of SSc were independently associated with mortality in multivariate logistic regression (P = 0.004 and 0.03, respectively). The Simplified Acute Physiology Score II (SAPS II), SOFA and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were good predictors of sepsis mortality in the investigated cohort (SAPS II AUC 0.772, P = 0.002; SOFA AUC 0.756, P = 0.004; APACHE II AUC 0.741, P = 0.007). Conclusions: In-hospital sepsis mortality is high in CTD patients. SSc diagnoses and SOFA were independently associated with mortality. Additionally, common ICU scores were good predictors for mortality. [ABSTRACT FROM AUTHOR]

Introduction: Monitoring of direct oral anticoagulants (DOACs) with calibrated anti‐Xa assay is limited by the high intra‐ and interindividual variations of the test results. Thrombin generation (TG) is a global hemostatic assay that reflects the patient´s individual coagulation status. The aim of this study was to investigate the influence of DOACs on TG measured with a fully automated assay system. Methods: All consecutive patients under apixaban and rivaroxaban coming to the outpatient coagulation center MVZ Limbach, Magdeburg, Germany between October 2017 and April 2020 were included. DOAC plasma levels were correlated with TG assessed using the fully automated Ceveron TG analyzer. Results: A total of 703 rivaroxaban and 252 apixaban containing plasma samples were included. There was a significant correlation between DOAC plasma levels and all TG parameters except for lag time regarding apixaban. Time to peak and peak thrombin followed an exponential regression curve, while this was linear for the endogenous thrombin potential (ETP). Apixaban showed a lower correlation coefficient for all TG parameters compared with rivaroxaban, and thrombin generation was less influenced by apixaban than rivaroxaban at plasma levels >100 ng/ml. The sensitivity and negative predictive value of normal TG parameters for the prediction of DOAC plasma levels <30 ng/ml was >85%. Conclusion: The present data show a moderate predominantly nonlinear correlation between TG parameters and plasma levels of apixaban and rivaroxaban. Rivaroxaban has a stronger effect on TG than apixaban. [ABSTRACT FROM AUTHOR]

Background: The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess. Objective: This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level. Methods: Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC—apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG. Results: The baseline TG before DOAC intake showed inter‐individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti‐Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti‐Xa inhibitors. All DOACs showed a nonlinear dose‐response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels. Conclusion: The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient‐specific baseline TG level and the drug‐specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation. [ABSTRACT FROM AUTHOR]

Introduction/Background: Vasculitis patients have a high risk for infections that may require intensive care unit (ICU) treatment in case of resulting sepsis. Since data on sepsis mortality in this patient group is limited, the present study investigated the clinical characteristics and outcomes of vasculitis patients admitted to the ICU for sepsis. Methods: The medical records of all necrotizing vasculitis patients admitted to the ICU of a tertiary hospital for sepsis in a 13-year period have been reviewed. Mortality was calculated and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. Moreover, the predictive power of common ICU scores was further evaluated. Results: The study included 34 patients with necrotizing vasculitis (mean age 69 + 9.9 years, 35.3% females). 47.1% (n = 16) were treated with immunosuppressives (mostly cyclophosphamide, n = 35.3%) and 76.5% (n = 26) received glucocorticoids. Rituximab was used in 4 patients (11.8%). The inhospital mortality of septic vasculitis patients was 41.2%. The Sequential Organ Failure Assessment (SOFA) score (p = 0.003) was independently associated with mortality in multivariate logistic regression. Acute Physiology And Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and SOFA scores were good predictors of sepsis mortality in the investigated vasculitis patients (APACHE II AUC 0.73, p = 0.02; SAPS II AUC 0.81, p < 0.01; SOFA AUC 0.898, p < 0.0001). Conclusions: Sepsis mortality was high in vasculitis patients. SOFA was independently associated with mortality in a logistic regression model. SOFA and other well-established ICU scores were good mortality predictors. [ABSTRACT FROM AUTHOR]

Introduction/Background: Patients with rheumatoid arthritis (RA) have a high risk of infections that may require intensive care unit (ICU) admission in case of resulting sepsis. Data regarding the mortality of these patients are very limited. This study investigated clinical characteristics and outcomes of patients with RA admitted to the ICU for sepsis and compared the results to a control cohort without RA. Methods: All patients with RA as well as sex-, age-, and admission year-matched controls admitted to the ICU of a university hospital for sepsis between 2006 and 2019 were retrospectively analyzed. Mortality was calculated for both the groups, and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. The positive predictive value of common ICU scores was also investigated. Results: The study included 49 patients with RA (mean age 67.2 ± 9.0 years, 63.3% females) and 51 matched controls (mean age 67.4 ± 9.5 years, 64.7% females). Among the patients with RA, 42.9% (n = 21) were treated with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and 30.6% (n = 15) received glucocorticoids only. Seven (14.3%) patients received biologic (b) DMARDs. The hospital mortality was higher among patients with RA (42.9% vs 15.7%, P = .0016). Rheumatoid arthritis was independently associated with mortality in multivariate logistic regression (P = .001). In patients with RA, renal replacement therapy (P = .024), renal failure (P = .027), and diabetes mellitus (P = .028) were independently associated with mortality. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were good predictors of sepsis mortality in patients with RA (APACHE II area under the curve [AUC]: 0.78, P = .001; SAPS II AUC: 0.78, P < .001; SOFA AUC 0.78, P < .001), but their predictive power was higher among controls. Conclusions: Hospital sepsis mortality was higher in patients with RA than in controls. Rheumatoid arthritis itself is independently associated with an increased sepsis mortality. Renal replacement therapy, renal failure, and diabetes were associated with an increased mortality. Common ICU scores were less well predictors of sepsis mortality in patients with RA compared to non-RA controls. [ABSTRACT FROM AUTHOR]

Summary: The safety of direct oral anticoagulants (DOACs) in patients after solid organ transplantation (SOT) is not well defined. This study aimed at describing the safety and efficacy of DOACs in patients after SOT. Patients after kidney and/or liver transplantation under maintenance immunosuppression treated with rivaroxaban (n = 26), apixaban (n = 20) and edoxaban (n = 1) were included. Clinical data were collected retrospectively and using a questionnaire. DOAC plasma levels and thrombin generation (TG) were measured in patients after SOT and compared with nontransplanted controls receiving DOACs. DOACs were administered for 84.6 patient‐years. Mean immunosuppressive trough levels after DOAC initiation increased from baseline by 18.8 ± 29.6% compared to 3.0 ± 16.5% in matched controls (P = 0.004), without significant differences in dose adjustments. No transplant rejection or significant change in liver or renal function was observed. There was one major bleeding after the observation period but no thromboembolic complication. DOAC plasma levels reached the expected range in all patients. The intrinsic hemostatic activity in transplanted patients was higher compared to nontransplant controls. Treatment with DOACs after SOT is safe and effective. Immunosuppressive trough levels should be monitored after DOAC initiation, particularly in the early phase after SOT. These data should be confirmed in a prospective study. [ABSTRACT FROM AUTHOR]

Patients with severe haemophilia A can nowadays achieve normal life expectancy thanks to current therapeutic options. Although emicizumab is widely used for bleeding prophylaxis to date4 there are still limited data about the use of emicizumab in patients with comorbidities,5 particularly in patients with advanced CKD with or without kidney replacement therapy. Although our findings support the use of emicizumab in haemodialysis patients without relevant non-selective proteinuria, data on more patients with a longer follow-up are needed to generally recommend the use of emicizumab in this patient cohort. [Extracted from the article]

Background: Albumin is a key regulator of fluid distribution within the extracellular space and has several properties beyond its oncotic activity. The accumulating evidence suggests that supplementation of albumin may provide survival advantages only when the insult is severe as in patients with septic shock.Methods/design: The randomized controlled multicentre study of albumin replacement therapy in septic shock (ARISS) investigates whether the replacement with albumin and the maintenance of its serum levels of at least 30 g/l for 28 days improve survival in patients with septic shock compared to resuscitation and volume maintenance without albumin. Adult patients (≥ 18 years) with septic shock are randomly assigned within a maximum of 24 h after the onset of septic shock after obtaining informed consents to treatment or control groups. Patients assigned to the treatment group receive a 60-g loading dose of human albumin 20% over 2-3 h. Serum albumin levels are maintained at least at 30 g/l in the ICU for a maximum of 28 days following randomization using 40-80 g human albumin 20% infusion. The control group is treated according to the usual practice with crystalloids as the first choice for the resuscitation and maintenance phase of septic shock. The primary endpoint is 90 days mortality and secondary endpoints include 28-day, 60-day, ICU, and in-hospital mortality, organ dysfunction/failure, total amount of fluid administration and total fluid balance in the ICU, and lengths of ICU and hospital stay. In total, 1412 patients need to be analysed, 706 per group. For the sample size estimation, a 15% reduction in 90-day mortality is assumed, i.e. an absolute reduction of 7.5% points to 42.5% (relative risk 1.18). Assuming a dropout rate of 15%, a total of 1662 patients need to be allocated.Discussion: The results of the clinical trial may influence the treatment of patients with septic shock. The expected improvement in patient survival may result in a reduction in the resources currently used in the treatment of these patients and in the socioeconomic burden of this disease.Trial Registration: ClinicalTrials.gov NCT03869385 . Registration on 18 July 2019. Protocol version: Final 3.0. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is a common complication of cancer. This study aimed to evaluate immature platelet fraction (IPF), mean platelet volume (MPV), P-selectin, D-dimer, and thrombin generation (TG) as predictive biomarkers for VTE and further the improvement of existing risk assessment models (RAMs). Methods: A prospective, observational, exploratory study was conducted on ambulatory cancer patients with indication for systemic chemotherapy. Baseline RAMs included the Khorana-, Vienna Cancer, Thrombosis-, Protecht-, ONKOTEV-, and Catscore. IPF, MPV, P-selectin, D-dimer, and TG were analysed at baseline and 3-month follow-up. Results: We enrolled 100 patients, of whom 89 completed the follow-up. Frequent tumour types were breast (30%), gastric (14%), gynaecological (14%), and colorectal (14%) cancer. Ten of the 89 patients (11.2%) developed VTE. The highest VTE rate was observed in patients with cholangiocarcinoma (3/5; 60%). Baseline D-dimer levels but not IPF, MPV, or P-selectin were associated with the risk of developing VTE (HR 6.9; p = 0.021). None of the RAMs showed statistical significance in predicting VTE. Peak thrombin and endogenous thrombin potential were lower in patients who developed VTE. Biomarker changes between baseline and follow-up were not associated with VTE risk. Conclusions: VTE risk was well predicted by baseline D-dimer levels. Adding D-dimer could improve existing RAMs to better identify patients who may benefit from primary VTE prophylaxis. The VTE risk among patients with cholangiocarcinoma should be further evaluated. [ABSTRACT FROM AUTHOR]

Background: Regional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques. Methods: In this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD. Results: Mean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups. Conclusion: CVVHD using a high cut-off dialyzer results in more effective middle molecule clearance than that with high-flux dialyzer. Trial registration: German Clinical Trials Register (, registered 26th November 2013) [ABSTRACT FROM AUTHOR]