Objectives This study aimed to demonstrate that the presence of late gadolinium enhancement (LGE) is a predictor of death and other adverse events in patients with suspected cardiac sarcoidosis. ...Background Cardiac sarcoidosis is the most important cause of patient mortality in systemic sarcoidosis, yielding a 5-year mortality rate between 25% and 66% despite immunosuppressive treatment. Other groups have shown that LGE may hold promise in predicting future adverse events in this patient group. Methods We included 155 consecutive patients with systemic sarcoidosis who underwent cardiac magnetic resonance (CMR) for workup of suspected cardiac sarcoid involvement. The median follow-up time was 2.6 years. Primary endpoints were death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator (ICD) discharge. Secondary endpoints were ventricular tachycardia (VT) and nonsustained VT. Results LGE was present in 39 patients (25.5%). The presence of LGE yields a Cox hazard ratio (HR) of 31.6 for death, aborted sudden cardiac death, or appropriate ICD discharge, and of 33.9 for any event. This is superior to functional or clinical parameters such as left ventricular (LV) ejection fraction (EF), LV end-diastolic volume, or presentation as heart failure, yielding HRs between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure), and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively. Except for 1 patient dying from pulmonary infection, no patient without LGE died or experienced any event during follow-up, even if the LV was enlarged and the LVEF severely impaired. Conclusions Among our population of sarcoid patients with nonspecific symptoms, the presence of myocardial scar indicated by LGE was the best independent predictor of potentially lethal events, as well as other adverse events, yielding a Cox HR of 31.6 and of 33.9, respectively. These data support the necessity for future large, longitudinal follow-up studies to definitely establish LGE as an independent predictor of cardiac death in sarcoidosis, as well as to evaluate the incremental prognostic value of additional parameters.
The purpose of this study was to compare different contrast agents for longitudinal liver and spleen imaging in a mouse model of liver metastasis.
Mice developing liver metastases underwent ...longitudinal micro-computed tomography imaging after injection of Fenestra LC, ExiTron nano 6000, or ExiTron nano 12000. Elimination times and contrast enhancement of liver and spleen were compared.
For all contrast agents, liver contrast peaked at approximately 4 hours and spleen contrast at 48 hours postinjection. A single dose of 100 μL of ExiTron nano 6000 or 12000 resulted in longstanding enhancement of liver and spleen tissue for longer than 3 weeks, whereas repeated injections of 400 μL of Fenestra LC were required to retain contrast at acceptable levels and allowed imaging of the liver/spleen for up to 2 and 9 days, respectively.
Both ExiTron nano agents provide longer and stronger contrast enhancement of liver and spleen compared to Fenestra LC, and they do so at a 75% lower injection volume in mice.
Objective To investigate the safety and short term outcome of high dose recombinant human erythropoietin (rhEpo) given shortly after birth and subsequently over the first 2 days for neuroprotection ...to very preterm infants. Study design Randomized, double masked phase II trial. Preterm infants (gestational age 26 0/7-31 6/7 weeks) were given rhEpo (nt = 229; 3000 U/kg body weight) or NaCl 0.9% (nc = 214) intravenously at 3, 12-18, and 36-42 hours after birth. Results There were no relevant differences between the groups for short-term outcomes such as mortality, retinopathy of prematurity, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. At day 7-10, we found significantly higher hematocrit values, reticulocyte, and white blood cell counts, and a lower platelet count in the rhEpo group. Conclusions Early high-dose rhEpo administration to very premature infants is safe and causes no excess in mortality or major adverse events. Trial registration ClinicalTrials.gov : NCT00413946.
The aims of this study were to evaluate the effectiveness of low-dose, contrast-enhanced (CE), time-resolved, three-dimensional magnetic resonance angiography (MRA) in the assessment of the abdominal ...aorta and its major branches at 3 T and to compare the results with those of high-spatial resolution CE MRA.
Twenty-two consecutive patients (eight men, 14 women; mean age, 43.9 +/- 17.9 years) underwent CE time-resolved three-dimensional MRA and high-spatial resolution three-dimensional MRA. Studies were performed using a 3-T magnetic resonance system; gadolinium-based contrast medium was administered at a dose of 3 to 5 mL for time-resolved MRA, followed by 0.1 mmol/kg gadopentetate dimeglumine for single-phase CE MRA. For analysis purposes, the abdominal arterial system was divided into 11 arterial segments, and image quality as well as the presence and degree of vascular pathology were evaluated by two independent magnetic resonance radiologists.
A total of 242 arterial segments were visualized with good image quality. Time-resolved MRA was able to visualize the majority of arterial segments with good definition in the diagnostic range. Vascular pathologies (stenosis, occlusion) or abnormal vascular anatomy was detected in 19 arterial segments, with good interobserver agreement (kappa = 0.78). All image findings were detected with time-resolved CE MRA by both observers and were confirmed by correlative imaging.
Low-dose, time-resolved MRA at 3 T yields rapid and important anatomic and functional information in the evaluation of the abdominal vasculature. Because of its limited spatial resolution, time-resolved MRA is inferior to CE MRA in demonstrating fine vascular details.
BACKGROUND:Despite the clinical importance of suicidal deep wrist injuries (DWIs), we currently do not know whether their injury patterns differ from accidental injuries.
METHODS:This retrospective ...study included all patients admitted to the Clinic of Plastic Surgery for acute treatment of a DWI from 2008 to 2016, except for isolated injuries to the palmaris longus (PL) and amputations. Intentionality of the injury was determined using documentation of psychiatric evaluations; cases that could not be categorized regarding intentionality were excluded.
RESULTS:About 20% of DWIs stemmed from suicide attempts, which involved the nondominant hand in 94.5%. Suicidal DWIs were more likely to involve the median nerve, radial artery, PL, and flexor carpi radialis (FCR), especially on the nondominant hand, but were less likely to involve the ulnar artery and nerve on the dominant hand. The effect of the protective structures PL/flexor carpi ulnaris on the median nerve/ulnar artery could be confirmed for suicidal DWIs, but intactness of the FCR was associated with increased radial artery injuries. Longitudinal cut orientation in suicidal DWIs was associated with more radial artery injuries, but fewer injuries to tendons and nerves. Frequencies of various other injury constellations are tabulated to aid in clinical assessment.
CONCLUSIONS:Suicidal and accidental DWIs differed in various aspects of injury pattern. Suicidal injuries were mostly localized to the nondominant radial side, and accidental injuries to the ulnar side. Also, the so-called protective structure FCR had the opposite effect in suicidal injuries. Thus, findings regarding injury patterns in accidental DWIs cannot be generalized to suicidal injuries.
Abstract We characterize 2 cases with sensorineural hearing loss and ophthalmologic findings. The clinicopathologic features revealed diagnosis of Susac's syndrome, a rare microangiopathy with ...cochlea, retinal, and brain affection. Diagnosis may be difficult because most specialists are not familiar with this angiopathy. However, the characteristic symptoms can mimic different pathologies, which may result in attention of radiologists, ophthalmologists, neurologists and otolaryngologists. In this report, we present 2 women with Susac's syndrome unveiled by audiometry, magnetic resonance imaging of the brain, and ophthalmologic findings. The course of the illness and a review of literature are presented.
Summary Background Preclinical data and results from non-randomised trials suggest that the multikinase inhibitor sorafenib might be an effective drug for the treatment of acute myeloid leukaemia. We ...investigated the efficacy and tolerability of sorafenib versus placebo in addition to standard chemotherapy in patients with acute myeloid leukaemia aged 60 years or younger. Methods This randomised, double-blind, placebo-controlled, phase 2 trial was done at 25 sites in Germany. We enrolled patients aged 18–60 years with newly diagnosed, previously untreated acute myeloid leukaemia who had a WHO clinical performance score 0–2, adequate renal and liver function, no cardiac comorbidities, and no recent trauma or operation. Patients were randomly assigned (1:1) to receive two cycles of induction therapy with daunorubicin (60 mg/m2 on days 3–5) plus cytarabine (100 mg/m2 on days 1–7), followed by three cycles of high-dose cytarabine consolidation therapy (3 g/m2 twice daily on days 1, 3, and 5) plus either sorafenib (400 mg twice daily) or placebo on days 10–19 of induction cycles 1 and 2, from day 8 of each consolidation, and as maintenance for 12 months. Allogeneic stem-cell transplantation was scheduled for all intermediate-risk patients with a sibling donor and for all high-risk patients with a matched donor in first remission. Computer-generated randomisation was done in blocks. The primary endpoint was event-free survival, with an event defined as either primary treatment failure or relapse or death, assessed in all randomised patients who received at least one dose of study treatment. We report the final analysis. This trial is registered with ClinicalTrials.gov , number NCT00893373 , and the EU Clinical Trials Register (2008-004968-40). Findings Between March 27, 2009, and Nov 28, 2011, 276 patients were enrolled and randomised, of whom nine did not receive study medication. 267 patients were included in the primary analysis (placebo, n=133; sorafenib, n=134). With a median follow-up of 36 months (IQR 35·5–38·1), median event-free survival was 9 months (95% CI 4–15) in the placebo group versus 21 months (9–32) in the sorafenib group, corresponding to a 3-year event-free survival of 22% (95% CI 13–32) in the placebo group versus 40% (29–51) in the sorafenib group (hazard ratio HR 0·64, 95% CI; 0·45–0·91; p=0·013). The most common grade 3–4 adverse events in both groups were fever (71 53% in the placebo group vs 73 54% in the sorafenib group), infections (55 41% vs 46 34%), pneumonia (21 16% vs 20 14%), and pain (13 10% vs 15 11%). Grade 3 or worse adverse events that were significantly more common in the sorafenib group than the placebo group were fever (relative risk RR 1·54, 95% CI 1·04–2·28), diarrhoea (RR 7·89, 2·94–25·2), bleeding (RR 3·75, 1·5–10·0), cardiac events (RR 3·46, 1·15–11·8), hand-foot-skin reaction (only in sorafenib group), and rash (RR 4·06, 1·25–15·7). Interpretation In patients with acute myeloid leukaemia aged 60 years or younger, the addition of sorafenib to standard chemotherapy has antileukaemic efficacy but also increased toxicity. Our findings suggest that kinase inhibitors could be a useful addition to curative treatment for acute myeloid leukaemia. Overall survival after long-term follow-up and strategies to reduce toxicity are needed to determine the future role of sorafenib in treatment of this disease. Funding Bayer HealthCare.
Summary Background Routine prophylactic platelet transfusion is the standard of care for patients with severe thrombocytopenia. We assessed the effect of a new strategy of therapeutic platelet ...transfusion on the number of transfusions and safety in patients with hypoproliferative thrombocytopenia. Methods We did a multicentre, open-label, randomised parallel-group trial at eight haematology centres in Germany. Patients aged 16–80 years, who were undergoing intensive chemotherapy for acute myeloid leukaemia or autologous haemopoietic stem-cell transplantation for haematological cancers, were randomly assigned via a computer-generated randomisation sequence to receive either platelet transfusion when bleeding occurred (therapeutic strategy) or when morning platelet counts were 10×109 per L or lower (prophylactic strategy). Investigators undertaking interventions were not masked to group assignment. The primary endpoint was the number of platelet transfusions. Analysis was by intention to treat. This trial is registered, NCT00521664. Findings 197 patients were assigned the prophylactic strategy and 199 the therapeutic strategy. Of 391 patients analysed, the therapeutic strategy reduced the mean number of platelet transfusions by 33·5% (95% CI 22·2–43·1; p<0·0001) in all patients (2·44 2·22–2·67 in prophylactic group vs 1·63 1·42–1·83 in therapeutic group), 31·6% (18·6–42·6; p<0·0001) in those with acute myeloid leukaemia (2·68 2·35–3·01 vs 1·83 1·58–2·10), and 34·2% (6·6–53·7; p=0·0193) in those who had had autologous transplantation (1·80 1·45–2·15 vs 1·18 0·82–1·55. We noted no increased risk of major haemorrhage in patients who had undergone autologous transplantation. In those with acute myeloid leukaemia, risk of non-fatal grade 4 (mostly CNS) bleeding was increased. We recorded 15 cases of non-fatal haemorrhage: four retinal in each transfusion group, and one vaginal and six cerebral in the therapeutic group. 12 patients died in the study: two from fatal cerebral haemorrhages in the therapeutic group, and ten (five in each treatment group) unrelated to major bleeding. Interpretation The therapeutic strategy could become a new standard of care after autologous stem-cell transplantation; however, prophylactic platelet transfusion should remain the standard for patients with acute myeloid leukaemia. The new strategy should be used by some haematology centres only if the staff are well educated and experienced in the new approach and can react in a timely way to first signs of CNS bleeding. Funding Deutsche Krebshilfe eV (German Cancer Aid).
Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in ...patients with established coronary heart disease remains less clear.
We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms (SNPs rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.
The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio HR 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies.
In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.
Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.
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