Feasibility of Goal-Directed Fluid Therapy in Patients with Transcatheter Aortic Valve Replacement - An Ambispective Analysis.

INTRODUCTION: Goal-directed fluid therapy (GDFT) has been shown to reduce postoperative complications. The feasibility of GDFT in transcatheter aortic valve replacement (TAVR) patients under general anesthesia has not yet been demonstrated. We examined whether GDFT could be applied in patients undergoing TAVR in general anesthesia and its impact on outcomes. METHODS: Forty consecutive TAVR patients in the prospective intervention group with GDFT were compared to 40 retrospective TAVR patients without GDFT. Inclusion criteria were age ≥ 18 years, elective TAVR in general anesthesia, no participation in another interventional study. Exclusion criteria were lack of ability to consent study participation, pregnant or nursing patients, emergency procedures, preinterventional decubitus, tissue and/or extremity ischemia, peripheral arterial occlusive disease grade IV, atrial fibrillation or other severe heart rhythm disorder, necessity of usage of intra-aortic balloon pump. Stroke volume and stroke volume variation were determined with uncalibrated pulse contour analysis and optimized according to a predefined algorithm using 250 ml of hydroxyethyl starch. RESULTS: Stroke volume could be increased by applying GDFT. The intervention group received more colloids and fewer crystalloids than control group. Total volume replacement did not differ. The incidence of overall complications as well as intensive care unit and hospital length of stay were comparable between both groups. GDFT was associated with a reduced incidence of delirium. Duration of anesthesia was shorter in the intervention group. Duration of the interventional procedure did not differ. CONCLUSION: GDFT in the intervention group was associated with a reduced incidence of postinterventional delirium.

Influence of a chronic beta-blocker therapy on perioperative opioid consumption - a post hoc secondary analysis.

BACKGROUND: Beta-blocker (BB) therapy plays a central role in the treatment of cardiovascular diseases. An increasing number of patients with cardiovascular diseases undergoe noncardiac surgery, where opioids are an integral part of the anesthesiological management. There is evidence to suggest that short-term intravenous BB therapy may influence perioperative opioid requirements due to an assumed cross-talk between G-protein coupled beta-adrenergic and opioid receptors. Whether chronic BB therapy could also have an influence on perioperative opioid requirements is unclear. METHODS: A post hoc analysis of prospectively collected data from a multicenter observational (BioCog) study was performed. Inclusion criteria consisted of elderly patients (≥ 65 years) undergoing elective noncardiac surgery as well as total intravenous general anesthesia without the use of regional anesthesia and duration of anesthesia ≥ 60 min. Two groups were defined: patients with and without BB in their regular preopreative medication. The administered opioids were converted to their respective morphine equivalent doses. Multiple regression analysis was performed using the morphine-index to identify independent predictors. RESULTS: A total of 747 patients were included in the BioCog study in the study center Berlin. 106 patients fulfilled the inclusion criteria. Of these, 37 were on chronic BB. The latter were preoperatively significantly more likely to have arterial hypertension (94.6%), chronic renal failure (27%) and hyperlipoproteinemia (51.4%) compared to patients without BB. Both groups did not differ in terms of cumulative perioperative morphine equivalent dose (230.9 (BB group) vs. 214.8 mg (Non-BB group)). Predictive factors for increased morphine-index were older age, male sex, longer duration of anesthesia and surgery of the trunk. In a model with logarithmised morphine index, only gender (female) and duration of anesthesia remained predictive factors. CONCLUSIONS: Chronic BB therapy was not associated with a reduced perioperative opioid consumption. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov ( NCT02265263 ) on the 15.10.2014 with the principal investigator being Univ.-Prof. Dr. med. Claudia Spies.

Feasibility of Goal-Directed Fluid Therapy in Patients with Transcatheter Aortic Valve Replacement - An Ambispective Analysis

ABSTRACT Introduction: Goal-directed fluid therapy (GDFT) has been shown to reduce postoperative complications. The feasibility of GDFT in transcatheter aortic valve replacement (TAVR) patients under general anesthesia has not yet been demonstrated. We examined whether GDFT could be applied in patients undergoing TAVR in general anesthesia and its impact on outcomes. Methods: Forty consecutive TAVR patients in the prospective intervention group with GDFT were compared to 40 retrospective TAVR patients without GDFT. Inclusion criteria were age ≥ 18 years, elective TAVR in general anesthesia, no participation in another interventional study. Exclusion criteria were lack of ability to consent study participation, pregnant or nursing patients, emergency procedures, preinterventional decubitus, tissue and/or extremity ischemia, peripheral arterial occlusive disease grade IV, atrial fibrillation or other severe heart rhythm disorder, necessity of usage of intra-aortic balloon pump. Stroke volume and stroke volume variation were determined with uncalibrated pulse contour analysis and optimized according to a predefined algorithm using 250 ml of hydroxyethyl starch. Results: Stroke volume could be increased by applying GDFT. The intervention group received more colloids and fewer crystalloids than control group. Total volume replacement did not differ. The incidence of overall complications as well as intensive care unit and hospital length of stay were comparable between both groups. GDFT was associated with a reduced incidence of delirium. Duration of anesthesia was shorter in the intervention group. Duration of the interventional procedure did not differ. Conclusion: GDFT in the intervention group was associated with a reduced incidence of postinterventional delirium.

Intraoperative Beat-to-Beat Pulse Transit Time (PTT) Monitoring via Non-Invasive Piezoelectric/Piezocapacitive Peripheral Sensors Can Predict Changes in Invasively Acquired Blood Pressure in High-Risk Surgical Patients.

BACKGROUND: Non-invasive tracking of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP, respectively) and to detect SBPIBP fluctuations. METHODS: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson's correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). RESULTS: Significant correlations between 1/PTT and SBPIBP were found for PES (r = 0.64) and PCS (r = 0.55) (p < 0.01), as well as MAPIBP/DBPIBP for PES (r = 0.6/0.55) and PCS (r = 0.5/0.45) (p < 0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease (0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). CONCLUSIONS: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus, PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

Changes of aortic hemodynamics after aortic valve replacement-A four dimensional flow cardiovascular magnetic resonance follow up study.

Objectives: Non-invasive assessment of aortic hemodynamics using four dimensional (4D) flow magnetic resonance imaging (MRI) provides new information on blood flow patterns and wall shear stress (WSS). Aortic valve stenosis (AS) and/or bicuspid aortic valves (BAV) are associated with altered aortic flow patterns and elevated WSS. Aim of this study was to investigate changes in aortic hemodynamics over time in patients with AS and/or BAV with or without aortic valve replacement. Methods: We rescheduled 20 patients for a second 4D flow MRI examination, whose first examination was at least 3 years prior. A total of 7 patients received an aortic valve replacement between baseline and follow up examination (=operated group = OP group). Aortic flow patterns (helicity/vorticity) were assessed using a semi-quantitative grading approach from 0 to 3, flow volumes were evaluated in 9 planes, WSS in 18 and peak velocity in 3 areas. Results: While most patients had vortical and/or helical flow formations within the aorta, there was no significant change over time. Ascending aortic forward flow volumes were significantly lower in the OP group than in the NOP group at baseline (NOP 69.3 mL ± 14.2 mL vs. OP 55.3 mL ± 1.9 mL p = 0.029). WSS in the outer ascending aorta was significantly higher in the OP group than in the NOP group at baseline (NOP 0.6 ± 0.2 N/m2 vs. OP 0.8 ± 0.2 N/m2, p = 0.008). Peak velocity decreased from baseline to follow up in the aortic arch only in the OP group (1.6 ± 0.6 m/s vs. 1.2 ± 0.3 m/s, p = 0.018). Conclusion: Aortic valve replacement influences aortic hemodynamics. The parameters improve after surgery.

High Central Venous Pressure after Cardiac Surgery Might Depict Hemodynamic Deterioration Associated with Increased Morbidity and Mortality.

BACKGROUND: Cardiac surgery patients represent a high-risk cohort in intensive care units (ICUs). Central venous pressure (CVP) measurement seems to remain an integral part in hemodynamic monitoring, especially in cardio-surgical ICUs. However, its value as a prognostic marker for organ failure is still unclear. Therefore, we analyzed postoperative CVP values after adult cardiac surgery in a large cohort with regard to its prognostic value for morbidity and mortality. METHODS: All adult patients admitted to our ICUs between 2006 and 2019 after cardiac surgery were eligible for inclusion in the study (n = 11,198). We calculated the median initial CVP (miCVP) after admission to the ICU, which returned valid values for 9802 patients. An ROC curve analysis for optimal cut-off miCVP to predict ICU mortality was conducted with consecutive patient allocation into a (a) low miCVP (LCVP) group (≤11 mmHg) and (b) high miCVP (HCVP) group (>11 mmHg). We analyzed the impact of high miCVP on morbidity and mortality by propensity score matching (PSM) and logistic regression. RESULTS: ICU mortality was increased in HCVP patients. In addition, patients in the HCVP group required longer mechanical ventilation, had a higher incidence of acute kidney injury, were more frequently treated with renal replacement therapy, and showed a higher risk for postoperative liver dysfunction, parametrized by a postoperative rise of ≥ 10 in MELD Score. Multiple regression analysis confirmed HCVP has an effect on postoperative ICU-mortality and intrahospital mortality, which seems to be independent. CONCLUSIONS: A high initial CVP in the early postoperative ICU course after cardiac surgery is associated with worse patient outcome. Whether or not CVP, as a readily and constantly available hemodynamic parameter, should promote clinical efforts regarding diagnostics and/or treatment, warrants further investigations.

Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BiKeR registry.

BACKGROUND: At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR). METHODS: JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 to March 2019, and baseline characteristics, effectiveness, and safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, and ACR-inactive disease definition. Safety assessments were based on adverse event (AE) reports. RESULTS: A total of 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug, and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after nine years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p = 0.3] and 52 SAEs (1.4/100PY; p = 0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p = 0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p = 0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p = 0.015) for inflammatory bowel disease, and 1.9/100PY and 1.4/100PY (p = 0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively. CONCLUSIONS: No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment.

Biologic Therapies in Polyarticular Juvenile Idiopathic Arthritis. Comparison of Long-Term Safety Data from the German BIKER Registry.

OBJECTIVE: Biologics have an important role in the treatment of juvenile idiopathic arthritis (JIA). Long-term safety data are limited. Direct comparison of different agents regarding occurrence of adverse events (AEs), especially of rare events, requires large quantities of patient years. In this analysis, long-term safety with regard to AE of special interest (AESI) was compared between different biologics. METHODS: Patients with nonsystemic JIA were selected from the German BIKER registry. Safety assessments were based on AE reports. Number of AEs, serious AEs, and 25 predefined AESIs, including medically important infection, uveitis, inflammatory bowel disease, cytopenia, hepatic events, anaphylaxis, depression, pregnancy, malignancy, and death, were analyzed. Event rates and relative risks were calculated using AEs reported after first dose through 70 days after last dose. RESULTS: A total of 3873 patients entered the analysis with 7467 years of exposure to biologics. The most common AESIs were uveitis (n = 231) and medically important infections (n = 101). Cytopenia and elevation of transaminases were more frequent with tocilizumab (risk ratio [RR] 8.0, 95% confidence interval [CI] 4.2-15, and RR 4.7, 95% CI 1.8-12.2, respectively). Anaphylactic events were associated with intravenous route of administration. In patients ever exposed to biologics, eight malignancies were reported. Six pregnancies have been documented in patients with tumor necrosis factor inhibitors. No death occurred in this patient cohort during observation. CONCLUSION: Surveillance of pharmacotherapy as provided by the BIKER registry is an import approach, especially for long-term treatment of children. Overall, tolerance was acceptable. Differences between biologics were noted and should be considered in daily patient care.

Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry.

OBJECTIVE: Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. METHODS: Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model. RESULTS: Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept. CONCLUSION: Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.

Local infiltration anaesthesia versus sciatic nerve and adductor canal block for fast-track knee arthroplasty: A randomised controlled clinical trial.

BACKGROUND: Local infiltration anaesthesia (LIA) was introduced as an innovative analgesic procedure for enhanced recovery after primary total knee arthroplasty (TKA). However, LIA has never been compared with analgesia based on an adductor canal catheter and a single-shot sciatic nerve block. OBJECTIVE: To evaluate two analgesic regimens for TKA comparing mobility, postoperative pain and patient satisfaction. DESIGN: Two-group randomised, controlled clinical trial. SETTING: Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Germany between April and August 2017. PATIENTS: Adults undergoing primary TKA under general anaesthesia were eligible for study participation. Exclusion criteria were heart insufficiency (New York Heart Association class >2), liver insufficiency (Child Pugh Score >B), evidence of diabetic polyneuropathy, severe obesity (BMI > 40 kg m), chronic opioid therapy for more than 3 months before scheduled surgery and allergy to local anaesthetics. INTERVENTIONS: Nerve block patients group (n=20) underwent surgery with two ultrasound-guided regional anaesthesia blocks: a single-shot sciatic nerve block with 20 ml of ropivacaine 0.75% combined with an adductor canal block with a catheter placed for less than 4 days with an infusion of ropivacaine 0.2% at a rate of 6 ml h. LIA patients (LIA group, n=20) received LIA of the knee capsule at the end of surgery with 150 ml of ropivacaine 0.2%. MAIN OUTCOME MEASURES: The primary endpoint was postoperative time to patient mobilisation (ability to walk) on the ward. RESULTS: Baseline characteristics were similar in each study group. Patients in both groups were mobilised to walk after TKA in similar time frames (LIA 24.0 h versus nerve block 27.1 h, 95% CI of difference -9.6 to 3.3 h). Maximum postoperative pain scores on exertion were higher in LIA patients with a mean 1.3 of 10 numerical rating scale points (95% CI 0.3 to 2.3, P = 0.010) as were intra-operative opioid requirements (LIA median 107 [IQR 100 to 268] mg versus nerve block median 78 [60 to 98] mg, P < 0.001). Patient satisfaction, postoperative oral morphine-equivalents and resting pain levels were comparable between groups. Anaesthesia induction time was reduced in LIA patients (LIA 10 min versus nerve block 35 min, 95% CI of difference 13 to 38 min, P < 0.001). CONCLUSION: Both analgesic regimens allow early mobilisation after TKA with high patient satisfaction. LIA shortened peri-operative time. Further research is required to optimise especially pain control during the later postoperative period with LIA. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03114306.

[PAPA syndrome with Crohn's disease and primary sclerosing cholangitis/autoimmune hepatitis overlap syndrome]. / PAPA-Syndrom mit Morbus Crohn und primär sklerosierender Cholangitis/Autoimmunhepatitis-Overlap-Syndrom.

BACKGROUND: The PAPA syndrome, an acronym for pyogenic sterile arthritis, pyoderma gangraenosum and acne, is an autosomal dominant hereditary disease which is caused by a mutation in the PSTPIP1 ("proline-serine-threonine phosphatase interacting protein 1") gene located on chromosome 15 and encodes the proline-serine-threonine phosphatase-interacting protein 1. An association with Crohn's disease (CD), autoimmune diseases of the liver and PAPA syndrome has not yet been reported in the literature. OBJECTIVE: To thoroughly investigate a family with three affected members (mother and 2 children) with newly diagnosed PAPA syndrome and intestinal and hepatobiliary symptoms. MATERIAL AND METHODS: We performed an in-depth phenotyping, dermatologic, radiologic, rheumatologic, gastroenterologic, histologic and genetic analysis in this family. RESULTS: All three family members could be newly diagnosed as suffering from PAPA syndrome and carried the known disease-causing mutation c.688G > A (p.Ala230Thr) in the PSTPIP1 gene. The younger son suffered from CD in addition to PAPA syndrome. The mother additionally suffered from ulcerative colitis (UC) and an overlap syndrome between autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). A mutation in in the NOD2 ("nucleotide binding oligomerization domain containing protein 2") gene could not be detected in any of the three persons affected. CONCLUSION: We extended the symptoms of PAPA syndrome to CD and autoimmune liver disease. These different disease entities might share a similar pathogenetic mechanism or even represent a new syndrome. This can be clarified in the future by screening patients with PAPA syndrome for intestinal and also hepatobiliary diseases.

Two-year Efficacy and Safety of Etanercept in Pediatric Patients with Extended Oligoarthritis, Enthesitis-related Arthritis, or Psoriatic Arthritis.

OBJECTIVE: The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample). RESULTS: There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported. CONCLUSION: Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.

Blood flow characteristics in the ascending aorta after TAVI compared to surgical aortic valve replacement.

Ascending aortic blood flow characteristics are altered after aortic valve surgery, but the effect of transcatheter aortic valve implantation (TAVI) is unknown. Abnormal flow may be associated with aortic and cardiac remodeling. We analyzed blood flow characteristics in the ascending aorta after TAVI in comparison to conventional stented aortic bioprostheses (AVR) and healthy subjects using time-resolved three-dimensional flow-sensitive cardiovascular magnetic resonance imaging (4D-flow MRI). Seventeen patients with TAVI (Edwards Sapien XT), 12 with AVR and 9 healthy controls underwent 4D-flow MRI of the ascending aorta. Target parameters were: severity of vortical and helical flow pattern (semiquantitative grading from 0 = none to 3 = severe) and the local distribution of systolic wall shear stress (WSSsystole). AVR revealed significantly more extensive vortical and helical flow pattern than TAVI (p = 0.042 and p = 0.002) and controls (p < 0.001 and p = 0.001). TAVI showed significantly more extensive vortical flow than controls (p < 0.001). Both TAVI and AVR revealed marked blood flow eccentricity (64.7 and 66.7%, respectively), whereas controls showed central blood flow (88.9%). TAVI and AVR exhibited an asymmetric distribution of WSSsystole in the mid-ascending aorta with local maxima at the right anterior aortic wall and local minima at the left posterior wall. In contrast, controls showed a symmetric distribution of WSSsystole along the aortic circumference. Blood flow was significantly altered in the ascending aorta after TAVI and AVR. Changes were similar regarding WSSsystole distribution, while TAVI resulted in less helical and vortical blood flow.

Efficacy and safety of etanercept in patients with the enthesitis-related arthritis category of juvenile idiopathic arthritis: results from a phase III randomized, double-blind study.

OBJECTIVE: To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA). METHODS: This was a 2-phase study in JIA patients with active, refractory ERA. Phase I was an open-label, uncontrolled 24-week study period in which all patients were administered etanercept. Patients considered to be treatment responders at week 24 according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement in juvenile arthritis entered the second phase, a 24-week randomized, double-blind, placebo-controlled withdrawal study, for an additional 24 weeks, for evaluation of the primary end point, occurrence of a disease flare from week 24 to week 48, based on the ACR preliminary definition of disease flare in juvenile arthritis. RESULTS: Forty-one patients were enrolled. At week 24, treatment with etanercept resulted in response rates of 93%, 93%, 80%, 56%, and 54% based on the ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria, respectively. In addition, a marked decrease in all disease activity measures was observed. The mean number of tender joints, swollen joints, and joints with active arthritis decreased by 91%, 97%, and 94%, respectively. Physician's global assessment of disease activity, parent's assessment of patient's overall well-being, and the Childhood Health Assessment Questionnaire disability index improved by 91%, 80%, and 86%, respectively. The number of tender enthesis sites and total scores for back pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Juvenile Arthritis Disease Activity Score based on 10-joint counts (JADAS10) decreased by 75%, 72%, 81%, 72%, 85%, and 87%, respectively. In phase II, 38 patients were randomly assigned to receive placebo (n = 18) or to continue receiving etanercept (n = 20). Up to week 48, 12 disease flares occurred, in 9 patients receiving placebo and 3 patients receiving etanercept (odds ratio 6.0, P = 0.02). There were no serious infections, malignancies, or deaths. CONCLUSION: In this study of patients with the ERA category of JIA, etanercept proved effective, as indicated by high ACR Pedi response rates and JADAS10 response rates at week 24. Patients who continued treatment with etanercept had significantly fewer flares than those who received placebo, although 50% of patients in the placebo group did not experience a flare. Treatment suspension may be a consideration for patients with the ERA category of JIA who achieve remission.

Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

OBJECTIVE: To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. METHODS: International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present. RESULTS: The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections. CONCLUSION: The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA.

Cardiovascular magnetic resonance in adults with previous cardiovascular surgery.

Cardiovascular magnetic resonance (CMR) is a versatile non-invasive imaging modality that serves a broad spectrum of indications in clinical cardiology and has proven evidence. Most of the numerous applications are appropriate in patients with previous cardiovascular surgery in the same manner as in non-surgical subjects. However, some specifics have to be considered. This review article is intended to provide information about the application of CMR in adults with previous cardiovascular surgery. In particular, the two main scenarios, i.e. following coronary artery bypass surgery and following heart valve surgery, are highlighted. Furthermore, several pictorial descriptions of other potential indications for CMR after cardiovascular surgery are given.

Blood flow characteristics in the ascending aorta after aortic valve replacement--a pilot study using 4D-flow MRI.

BACKGROUND: Aortic remodeling after aortic valve replacement (AVR) might be influenced by the postoperative blood flow pattern in the ascending aorta. This pilot study used flow-sensitive four-dimensional magnetic resonance imaging (4D-flow) to describe ascending aortic flow characteristics after various types of AVR. METHODS: 4D-flow was acquired in 38 AVR patients (n=9 mechanical, n=8 stentless bioprosthesis, n=14 stented bioprosthesis, n=7 autograft) and 9 healthy controls. Analysis included grading of vortex and helix flow (0-3 point scale), assessment of systolic flow eccentricity (1-3 point scale), and quantification of the segmental distribution of peak systolic wall shear stress (WSS(peak)) in the ascending aorta. RESULTS: Compared to controls, mechanical prostheses showed the most distinct vorticity (2.7±0.5 vs. 0.7±0.7; p<0.001), while stented bioprostheses exhibited most distinct helicity (2.6±0.7 vs. 1.6±0.5; p=0.002). Instead of a physiologic central flow, all stented, stentless and mechanical prostheses showed eccentric flow jets mainly directed towards the right-anterior aortic wall. Stented and stentless prostheses showed an asymmetric distribution of WSS(peak) along the aortic circumference, with significantly increased local WSS(peak) where the flow jet impinged on the aortic wall. Local WSS(peak) was higher in stented (1.4±0.7 N/m(2)) and stentless (1.3±0.7 N/m(2)) compared to autografts (0.6±0.2 N/m(2); p=0.005 and p=0.008) and controls (0.7±0.1 N/m(2); p=0.017 and p=0.027). Autografts exhibited lower absolute WSS(peak) than controls (0.4±0.1 N/m(2) vs. 0.7±0.2 N/m(2); p=0.003). CONCLUSIONS: Flow characteristics in the ascending aorta after AVR are different from native aortic valves and differ between various types of AVR.