Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Good's syndrome: an uncommon cause of therapy-resistant diarrhoea.

Diarrhoea is a common symptom for which the aetiology will be straightforward in many cases. However, when a common aetiology is not found, the wide variety of other options can feel like finding a needle in a haystack. In this case report, we describe a patient who was referred to our centre with therapy-resistant, secretory diarrhoea, which was the presenting symptom of Good's syndrome, a rare form of adult-onset immunodeficiency associated with thymoma. The conclusions from this case report give direction for 'finding the needle' and contribute to a focused approach to patients who present with therapyresistant diarrhoea.

The myelodysplastic syndromes flow cytometric score: a three-parameter prognostic flow cytometric scoring system.

The prognosis of myelodysplastic syndromes (MDS) is currently estimated by using the revised International Prognostic Scoring System (IPSS-R). Several studies have shown that further refinement of prognostication for MDS can be achieved by adding flow cytometric parameters. However, widespread implementation of flow cytometry for the prognosis of MDS is hampered by complexity of the analysis. Therefore, the aim of this study was to construct a robust and practical flow cytometric score that could be implemented as a routine procedure. To achieve this, bone marrow aspirates of 109 MDS patients were analyzed by flow cytometry. A second cohort consisting of 103 MDS patients was used to validate the MDS flow cytometric score (MFS). The parameters forming the MFS were sideward light scatter and CD117 expression of myeloid progenitor cells and CD13 expression on monocytes. Three MFS risk categories were formed. Patients with MDS and intermediate MFS scores had significantly better overall survival (OS) compared with the patients with high MFS scores. The MFS further refined prognostication within the IPSS-R low-risk category, by identifying patients with worse OS in case of high MFS. In conclusion, a practical three parameter flow cytometric prognostic score was constructed enabling further refinement of prognostication of MDS.

Emergent endovascular repair of ruptured abdominal and thoracic aortic aneurysms in a single center: midterm outcomes.

OBJECTIVE: Endovascular therapies may offer distinct advantages in acute aortic syndromes. In this paper, we present our experience with emergent endovascular repair of both abdominal and thoracic aortic ruptures and report early and midterm out comes. METHODS: Data from all patients (n=96) who were treated by endovascular procedures between 2004 to 2012 were prospectively collected and early-midterm outcomes of the emergency (e) interventions for both abdominal (EVAR) and thoracic (TEVAR) aortic ruptures (n=20) were retrospectively analysed. RESULTS: The mean age was 65 +- 11 years (range: 27-77 years)and 18 patients (90%) were male. Mean follow-up duration was 28 ± 21.2 months (range=1-57). Thirteen patients were treated by eEVAR (65%) and 7 by eTEVAR (35%). One patient who had a rupture of the aneurysm at arcus aorta level was treated by hybrid procedure (eTEVAR+ debranching).The hospital mortality rate was 20% (n=4) for all cases, 23.0% (n=3) for eEVAR and 14.2% (n=1) for eTEVAR. In the follow-up period, 3 patients (15.0%) had reinterventions. DISCUSSION: Reinterventions and the necessity of close follow-up are the disadvantages of endovascular procedures.Even if that is the case, we believe that eEVAR eTEVAR in the acute setting of ruptured aorta in patients with suitable anatomy is a lifesaving option.

Azacitidine results in comparable outcome in newly diagnosed AML patients with more or less than 30% bone marrow blasts.

The efficacy of azacitidine has been demonstrated in acute myeloid leukemia (AML) patients with 20-30% bone marrow (BM) blasts, but limited data is available on patients with ≥30% blasts. We analyzed 55 newly diagnosed AML patients, treated with azacitidine. The overall response rate was 42%. Median overall survival (OS) was 12.3 months. We confirmed poor-risk cytogenetics, therapy-related AML, performance score ≥2, and white blood cell count ≥15×10(9)/L as independent adverse predictors for OS. The BM blast percentage, however, had no impact on OS (P=0.55). In conclusion, administration of azacitidine is effective in AML patients with 20-30% and >30% BM blasts.

Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group.

Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefore, a working group was initiated (Amsterdam, 2008) to discuss and propose standards for FC in MDS. In 2009 and 2010, representatives from 23, mainly European, institutes participated in the second and third European LeukemiaNet (ELN) MDS workshops. In the present report, minimal requirements to analyze dysplasia are refined. The proposed core markers should enable a categorization of FC results in cytopenic patients as 'normal', 'suggestive of', or 'diagnostic of' MDS. An FC report should include a description of validated FC abnormalities such as aberrant marker expression on myeloid progenitors and, furthermore, dysgranulopoiesis and/or dysmonocytopoiesis, if at least two abnormalities are evidenced. The working group is dedicated to initiate further studies to establish robust diagnostic and prognostic FC panels in MDS. An ultimate goal is to refine and improve diagnosis and prognostic scoring systems. Finally, the working group stresses that FC should be part of an integrated diagnosis rather than a separate technique.

Endovascular stent-graft treatment of type A dissection: case report and review of literature.

We report a successful endovascular stent-graft treatment of a patient with type A dissection with primary entry tear at the ascending aorta. Simultaneous coronary stenting was performed. A literature review was performed and the possible use of endovascular treatment for ascending aortic dissections is discussed.

Surgical management of intravenous leiomyoma with cardiac extension. Do we need total circulatory arrest?

Intravenous leiomyoma of the uterus is a histologically benign, smooth-muscle tumor and may extend through the inferior vena cava into the right atrium. Surgical treatment is mandatory and single-stage resection of the tumor has gained wide acceptance as a safe and easy procedure. We describe a single-stage surgical procedure for an intravenous leiomyoma extending to the right atrium diagnosed in a routine control after myomectomy.

Congenital intrapericardial left atrial appendage aneurysm.

Congenital true aneurysms of left atrial appendage are very rare. Abnormal cardiac silhouette on the chest roentgenograph is usually an important clue for the diagnosis. They are commonly associated with supraventricular arrhythmias and life-threatening systemic embolization. We report here the surgically-corrected case of a patient with congenital left atrial appendage aneurysm.

Hybrid treatment of ascending aortic pseudoaneurysm: endovascular stent-graft placement and extraanatomic reconstruction without sternotomy.

Conventional surgical repair of ascending aortic pseudoaneurysms following prior cardiac operations is performed with a high operative mortality. We report a 67 year old female patient with an ascending aortic pseudoaneurysm detected 3 years after coronary bypass surgery. The patient was treated with ascending aortic endovascular stent graft placement and extraanatomic reconstruction of supraaortic branches without using sternotomy.

EuroSCORE overestimates the cardiac operative risk.

INTRODUCTION: It was the purpose of our study to assess the validity of EuroSCORE (European system for cardiac operative risk evaluation) in our patient population. MATERIALS AND METHODS: Between March 1999 and August 2001, information on risk factors and mortality was collected for 1123 consecutive adult patients undergoing heart surgery with cardiopulmonary bypass. EuroSCORE was used for risk stratification. Mean age +/- standard deviation was 58.6 +/- 10.9 and 29.1% of the patients were female. The area under the receiver operating characteristic (ROC) curve was calculated as an index for the predictive value of the scoring system. RESULTS: The area under the ROC curve was 0.824 for all patients and 0.828 for the isolated CABG subgroup which shows an excellent predictive ability. When the scoring system was applied in low, medium, and high risk groups, there was no overlap between 95% confidence intervals of observed and expected mortality in all three groups both for the isolated CABG cases and for all patients. Decreased left ventricular ejection fraction, emergent operation, and preoperative unstable angina requiring i.v. nitrate treatment were significant predictive variables for early mortality. CONCLUSION: EuroSCORE is a simple and objective system for predicting the risk of heart surgery. The predictive power of the EuroSCORE is excellent, however it seems that mortality is considerably overestimated by this score.

Effect of partial oxygen supply on mitochondrial electron transport system during complete cardiac ischemia.

During complete ischemia we assessed myocardial utilization of the small amount of oxygen available. We also determined whether blood cardioplegia has any advantage over crystalloid cardioplegia in this setting. Patients with preserved left ventricular myocardial function and without anterolateral wall infarct or aneurysm were included to the study. Intermittent cold blood and crystalloid cardioplegia were used in 10 patients (group BC) and 9 patients (group CC), respectively. From myocardial biopsies, obtained before and after ischemia, complete electron transport system (ETS) enzyme activities (NDH, SDH, NCCR, SCCR, and COX) and lactate content were analyzed. Biochemical and hemodynamic analyses also were done. Myocardial and blood temperatures were monitored. Ischemic time was longer in group CC (p < 0.05). There were no important differences in biochemical and hemodynamic variables between the two groups. In addition, there was no difference in NDH and SDH activities as well as COX/SCCR and COX/RS-NCCR ratios between the two groups before and after ischemia. After Ischemia, RS-NCCR in group CC and SCCR and COX activities in both groups were lower than the control. For all enzymes, activity change ratios were not different between groups. Myocardial lactate content was increased in both groups after ischemia. However, the increase in group BC was less (p < 0.01). Based on our findings, we believe that the superiority of blood cardioplegia over crystalloid cardioplegia does not depend on oxygen content, but on other factors such as buffering and free oxygen radical scavenger effects among others. However, with the warm and continuous blood cardioplegia technique, oxygen content might be more important.

Use of color Doppler imaging in assessment of preoperative and postoperative flow characteristics of internal thoracic artery in myocardial revascularization.

Between January 1993 and February 1993, the left internal thoracic arteries of 40 consecutive patients scheduled for aortocoronary bypass operation were examined by transthoracic B-mode imaging. Perioperative measurements correlated well with preoperative noninvasive measurements (r = 0.914). In the postoperative period, B-mode images could not be obtained in 17 (44.7%) of 38 patients. Adequate Doppler spectra of the internal thoracic artery were obtained in all patients preoperatively and in 36 (94.7%) of 38 patients postoperatively. Preoperatively a triphasic wave form was obtained with a large systolic peak followed by small reversed and diastolic components in all patients. Postoperatively this triphasic wave form had been converted into a combined systolic-diastolic wave form. In all patients peak systolic velocity of the internal thoracic artery decreased (96.4 +/- 15.3 vs 64.2 +/- 18.9 cm/sec., P < 0.05), and peak diastolic velocity increased (21.7 +/- 8.8 vs 28.3 +/- 11.2 cm/sec., P < 0.05) significantly in the postoperative period as compared with the preoperative values. A slight decrease in peak systolic and diastolic velocities was detected at twelve months postoperatively. This study indicates that transthoracic B-mode imaging and Doppler spectrum analysis are reliable techniques in the preoperative and postoperative assessment of the internal thoracic artery in myocardial revascularization.

[Use of sternal zipper in open heart surgery]. / Application du fermoir sternal au cours de la chirurgie à coeur ouvert.

A sternal zipper was used in 50 patients with an unstable haemodynamic condition after open heart surgery. The patients were 19 women and 31 men (average age 51.6 years, range 7 to 67 years). The indications for surgery were aortocoronary bypass in 25 cases, replacement of the ascending aorta in 7 cases, valve replacement in 16 cases and correction of congenital heart disease in 2 cases. Twenty eight patients required circulatory assistance. The sternal zipper was used for 4 to 72 hours (average 29.5 hours) and mediastinal toilet was performed at least every 24 hours. At each opening of the zipper, 3 bacteriological swabs were taken from 3 different sites in the mediastinum and sent for culture. Global mortality was 36% (N = 18). The cause of death was a low output syndrome in 12 cases, hepatic and renal failure in 2 cases, resistant arrhythmia in 1 case, neurological complication in 1 case and septicaemia in 2 cases. There was one late death 3 months after hospital discharge which was attributed to a cardiac arrhythmia. The sternal zipper would seem to be a valuable option when the operative conditions are difficult, allowing the chest to remain open, so preventing cardiac compression during a critical period.