Occasionally, under normal physiologic conditions, slightly higher pressures in the left atrium can translate into a left-to-right shunt. 3 4 If right atrial pressure rises, the foramen ovale may ...open and there is potential for right-to-left shunting, the most devastating complication of which is stroke from paradoxical embolism. 5 6 Transthoracic echocardiography (TTE) is commonly the first imaging modality used to assess PFOs. The two other defects, sinus venosus and coronary sinus subtypes, physiologically behave as interatrial septal defects but do not involve a developmental abnormality of the interatrial septum per se.\n The four types of ASDs-ostium primum, ostium secundum, sinus venosus, and unroofed coronary sinus ASD-can be differentially detected and diagnosed using a combination of imaging modalities including transthoracic echocardiography (TTE), transoesophageal echocardiography (TOE), and/or CT.
Two cases of in-stent restenosis of a coronary artery bypass vein graft following beta (β) brachytheraphy are presented. Previously unreported histopathology of directed atherectomy specimens of such ...restenotic lesions and a discussion of their proposed significance form the basis of this report.
Allograft-specific regulatory T cells (T
cells) are crucial for long-term graft acceptance after transplantation. Although adoptive T
cell transfer has been proposed, major challenges include ...graft-specificity and stability. Thus, there is an unmet need for the direct induction of graft-specific T
cells. We hypothesized a synergism of the immunotolerogenic effects of rapamycin (mTOR inhibition) and plerixafor (CXCR4 antagonist) for T
cell induction. Thus, we performed fully-mismatched heart transplantations and found combination treatment to result in prolonged allograft survival. Moreover, fibrosis and myocyte lesions were reduced. Although less CD3
T cell infiltrated, higher T
cell numbers were observed. Noteworthy, this was accompanied by a plerixafor-dependent plasmacytoid dendritic cells-(pDCs)-mobilization. Furthermore, in vivo pDC-depletion abrogated the plerixafor-mediated T
cell number increase and reduced allograft survival. Our pharmacological approach allowed to increase T
cell numbers due to pDC-mediated immune regulation. Therefore pDCs can be an attractive immunotherapeutic target in addition to plerixafor treatment.
Background: In ST-segment–elevation myocardial infarction (STEMI), infarct size correlates directly with heart failure and mortality. Preclinical testing has shown that, in comparison with ...reperfusion alone, mechanically unloading the left ventricle (LV) before reperfusion reduces infarct size and that 30 minutes of unloading activates a cardioprotective program that limits reperfusion injury. The DTU-STEMI pilot trial (Door-To-Unload in STEMI Pilot Trial) represents the first exploratory study testing whether LV unloading and delayed reperfusion in patients with STEMI without cardiogenic shock is safe and feasible. Methods: In a multicenter, prospective, randomized exploratory safety and feasibility trial, we assigned 50 patients with anterior STEMI to LV unloading by using the Impella CP followed by immediate reperfusion (U-IR) versus delayed reperfusion after 30 minutes of unloading (U-DR). The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events at 30 days. Efficacy parameters included the assessment of infarct size by using cardiac magnetic resonance imaging. Results: All patients completed the U-IR (n=25) or U-DR (n=25) protocols with respective mean door-to-balloon times of 72 versus 97 minutes. Major adverse cardiovascular and cerebrovascular event rates were not statistically different between the U-IR versus U-DR groups (8% versus 12%, respectively, P =0.99). In comparison with the U-IR group, delaying reperfusion in the U-DR group did not affect 30-day mean infarct size measured as a percentage of LV mass (15±12% versus 13±11%, U-IR versus U-DR, P =0.53). Conclusions: We report that LV unloading using the Impella CP device with a 30-minute delay before reperfusion is feasible within a relatively short time period in anterior STEMI. The DTU-STEMI pilot trial did not identify prohibitive safety signals that would preclude proceeding to a larger pivotal study of LV unloading before reperfusion. An appropriately powered pivotal trial comparing LV unloading before reperfusion to the current standard of care is required. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03000270.
IntroductionPercutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) has been a major challenge due to technical difficulties with increased complication rates. Approximately ...10-15% of patients with acute myocardial infarction (AMI) have CTO. There is limited data comparing the impact of AMI in patients with CTO.HypothesisWe aimed to perform a trend analysis from a national registry comparing outcomes of PCI of CTO in patients with and without AMI.MethodsAll patients with a diagnosis of CTO were identified from National Inpatient Sample (NIS) 2007-2010 database using 9th revision of International Classification of Diseases (ICD) code 414.2. Patients with a primary diagnosis of ST-segment elevation AMI were extracted using ICD 9 code 410.x1 and only patients who underwent PCI were included. Differences in demographic and traditional risk factors were studied between the 2 groups. Primary outcomes of interest were in-hospital mortality, cardiac arrest and development of acute kidney injury (AKI).ResultsFrom 2007 to 2010, CTO was identified in 382,883 patients, among which 138,948 (36%) patients had AMI as primary diagnosis. Mean age was 66.3±0.1 years and 28% were females. There was a trend in increased prevalence of all traditional risk factors in patients with CTO and without AMI. However, length of stay (4.9±0.03 vs 4.3±0.02), in-hospital mortality (4% vs 1.5%), cardiac arrest (3.5% vs 1.2%) and prevalence of AKI (10.1% vs 7.5%) were significantly increased in patients with CTO and AMI (p<0.0001). The presence of AMI in CTO predicted more AKI after PCI even after adjusting for all risk factors OR 1.66 (156-1.76); p=0.000.ConclusionsPresence of AMI in patients with CTO was associated with poor clinical outcomes including in-hospital mortality, cardiac arrest, prolonged hospital stay, and development of AKI. Additional studies are needed to further corroborate these findings.
The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function ...over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN. Data were analyzed by Cox-regression models. Follow-up data were available for 149 participants, representing 92% of the patients originally randomized. Median follow-up was 7.4 years (inter quartile range 5.7 to 8.3 years). The primary endpoint was reached in 36 of 72 patients randomized to supportive care and 35 of 77 patients randomized to additional immunosuppression (hazard ratio 1.20; 95% confidence interval 0.75 to 1.92). ESKD occurred in 17 of the patients with supportive care and in 20 of the patients with additional immunosuppression. Additionally, the rates of eGFR loss over 40% and annual eGFR loss did not differ between groups. Two patients died with supportive care and three with additional immunosuppression. Thus, within the limitations of a retrospective study, over a follow-up of up to ten years, and using an adapted primary endpoint, we failed to detect differences in key clinical outcomes in IgAN patients randomized to receive added immunosuppression on top of supportive care versus supportive care alone.
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Liver transplant patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) early post-operatively are at high risk for bleeding. Using heparin for anticoagulation ...during CRRT may contribute to the increased bleeding risk. Regional anticoagulation with citrate may decrease the risk of bleeding. However, citrate anticoagulation may be associated with metabolic complications in patients with liver impairment. The aim of the study was to evaluate the safety and efficacy of citrate anticoagulation in liver transplant patients.
All liver transplant recipients transplanted between November 2004 and August 2007, requiring CRRT and using citrate as the anticoagulant were included in this retrospective study. Demographic data, CRRT specific and metabolic data were collected and analysed.
Sixty-eight patients (40 male/28 female) with a mean age of 47.1±11.8 years and a Model of End-stage Liver Disease score of 23±9 developed post-operative AKI requiring CRRT using citrate as the anticoagulant. The median duration on CRRT was 8 days (range 1-39 days) with a mean circuit life of 22.7±14.6 h. There was no relevant time trend of serum sodium, potassium, calcium, bicarbonate and pH values during CRRT. Bleeding occurred in 8 of 68 (11.7%) patients during CRRT.
Regional citrate anticoagulation for CRRT in the early post-operative period after liver transplantation is effective and safe. Therefore, the general exclusion of citrate anticoagulation during CRRT in patients after liver transplantation is not justified.
Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory ...syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.
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