Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report

Hypereosinophilic syndromes are a heterogeneous group of uncommon disorders characterized by the presence of marked peripheral blood eosinophilia, tissue eosinophilia, or both, resulting in a wide variety of clinical manifestations. Although corticosteroids are the first-line therapy for many of these disorders, approaches to the treatment of patients who do not tolerate or are unresponsive to corticosteroids are poorly standardized. A multidisciplinary group of 37 clinicians and scientists participated in a workshop held in May 2005 in Bern, Switzerland to discuss current and future approaches to therapy for 3 eosinophil-mediated disorders: hypereosinophilic syndrome, Churg-Strauss syndrome, and eosinophil-associated gastrointestinal disease. The goal of the workshop was to summarize available data regarding treatment of these disorders to identify the most promising therapies and approaches for further study. There was consensus among all of the participants that the identification of markers of disease progression to assess treatment responses is a research priority for all 3 disorders. Furthermore, the need for newer therapeutic strategies and novel drugs, as well as multicenter trials to assess all treatment modalities, was emphasized.

Impact of weather and climate on the incidence of acute coronary syndromes

BACKGROUND: First investigations of the interactions between weather and the incidence of acute myocardial infarctions date back to 1938. The early observation of a higher incidence of myocardial infarctions in the cold season could be confirmed in very different geographical regions and cohorts. While the influence of seasonal variations on the incidence of myocardial infarctions has been extensively documented, the impact of individual meteorological parameters on the disease has so far not been investigated systematically. Hence the present study intended to assess the impact of the essential variables of weather and climate on the incidence of myocardial infarctions. METHODS: The daily incidence of myocardial infarctions was calculated from a national hospitalization survey. The hourly weather and climate data were provided by the database of the national weather forecast. The epidemiological and meteorological data were correlated by multivariate analysis based on a generalized linear model assuming a log-link-function and a Poisson distribution. RESULTS: High ambient pressure, high pressure gradients, and heavy wind activity were associated with an increase in the incidence of the totally 6560 hospitalizations for myocardial infarction irrespective of the geographical region. Snow- and rainfall had inconsistent effects. Temperature, Foehn, and lightning showed no statistically significant impact. CONCLUSIONS: Ambient pressure, pressure gradient, and wind activity had a statistical impact on the incidence of myocardial infarctions in Switzerland from 1990 to 1994. To establish a cause-and-effect relationship more data are needed on the interaction between the pathophysiological mechanisms of the acute coronary syndrome and weather and climate variables.

Decision-making in amnesia: do advantageous decisions require conscious knowledge of previous behavioural choices?

Previous work has reported that in the Iowa gambling task (IGT) advantageous decisions may be taken before the advantageous strategy is known [Bechara, A., Damasio, H., Tranel, D., ; Damasio, A. R. (1997). Deciding advantageously before knowing the advantageous strategy. Science, 275, 1293-1295]. In order to test whether explicit memory is essential for the acquisition of a behavioural preference for advantageous choices, we measured behavioural performance and skin conductance responses (SCRs) in five patients with dense amnesia following damage to the basal forebrain and orbitofrontal cortex, six amnesic patients with damage to the medial temporal lobe or the diencephalon, and eight control subjects performing the IGT. Across 100 trials healthy participants acquired a preference for advantageous choices and generated large SCRs to high levels of punishment. In addition, their anticipatory SCRs to disadvantageous choices were larger than to advantageous choices. However, this dissociation occurred much later than the behavioural preference for advantageous alternatives. In contrast, though exhibiting discriminatory autonomic SCRs to different levels of punishment, 9 of 11 amnesic patients performed at chance and did not show differential anticipatory SCRs to advantageous and disadvantageous choices. Further, the magnitude of anticipatory SCRs did not correlate with behavioural performance. These results suggest that the acquisition of a behavioural preference--be it for advantageous or disadvantageous choices--depends on the memory of previous reinforcements encountered in the task, a capacity requiring intact explicit memory.

The syndromology of anorectal malformations revisited: from patterns of associated malformations to the recognition of syndromes

ackground: Although the frequency of associated malformation is high, the incidence of inheritable syndromes is widely underestimated in children with anorectal malformation (ARM). Data sources: OMIM database, patient records and charts of the Department of Pediatric Surgery, Johannes Gutenberg-University, Mainz, Germany. Methods: We analyzed all associations, sequences and syndromes listed in the OMIM database that can be accompanied by ARM. A large cohort of children born with ARM was then retrospectively investigated as to the type of ARM, presence of additional malformations and possible categorization as a syndrome, sequence or association. For this process a syndrome finder was developed and employed. This simplistic tool allows for a rapid first check of possible syndromes before a more complex analysis is started using the OMIM database and consulting specialists. Results: Among 317 children with ARM, associated malformations were present in 77.7% of 127 children with high ARM, in 68.7% of 32 with intermediate ARM, and in 25.3% of 158 with a low type ARM. Three or more organ systems were involved in 29.1% children with high type ARM and 25% with intermediate ARM and 8.2% with a low type ARM. An association of the vertebral anal tracheo-esophageal renal (VATER) and vertebral anal cardiac tracheo-esophageal renal limb (VACTERL) type was found in a total of 35 patients. Before analysis, 11 syndromes and 35 associations which were not clear previously in this patient cohort were described. In other 17 patients, 14 syndromes and 3 associations were identified. Conclusions: The high number of only retrospectively identified syndromes suggests that a routine search is necessary in every patient with ARM and additional malformations.

Novel approaches to therapy of hypereosinophilic syndromes

There has been recent progress in the understanding of the pathogenesis of the hypereosinophilic syndromes (HES). This led to the distinction of subgroups, in which the underlying cause has been identified. Consequently, new treatment options became available, such as imatinib and mepolizumab, which proved to be promising. This article summarizes these new pharmacologic approaches to the therapy of HES.

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.

The impact of statin treatment on presentation mode and early outcomes in acute coronary syndromes

OBJECTIVES: The role of statin use in the treatment of acute coronary syndromes (ACS) is not clear. The aim of our study was to evaluate the role of statins in ACS. METHODS: Using data from the Acute Myocardial Infarction in Switzerland (AMIS Plus) Project, we compared the effects of chronic statin use, statin therapy after admission and no statin therapy on presentation mode and outcomes in ACS. RESULTS: Available data from the period 2001-2006 including 11,603 patients were analyzed. Major cardiac event rates and in-hospital mortality were more common in statin-naive patients compared to patients who received statins. CONCLUSIONS: Our results support the importance of statin treatment in ACS. Chronic statin therapy seems to alter the initial presentation of ACS but it is questionable whether it provides an additional effect on early outcomes compared to the establishment of statin therapy after admission in statin-naive patients.

[Evaluation of the "Schema-focused Emotive Behavioural Therapy" (SET) for Patients with Personality Disorders: Results of a Randomised Controlled Trial.]

The "Schema-focussed Emotive Behavioral Therapy" (SET) was developed by our research group as a new group therapy approach for patients with personality disorders from all clusters (A to C; DSM-IV). It was evaluated in a randomised controlled study (n = 93). Data were collected before and after treatment as well as one year after study entry. A completer analysis was conducted with matched subgroups (n = 60). After therapy, SET patients improved in the outcome domains interactional behavior, strain, and symptomatic complaints (IIP-D, GAF, VEV-VW, BSI-P). Furthermore, they showed a significant lower dropout rate. At the follow-up assessment, Cluster C patients of the experimental group deteriorated with regard to symptomatic complaints (BSI-P). In contrast, cluster B patients improved more over time compared to control subjects. SET seems to be an adequate and effective group therapy with effects that seem to be stable over time, especially for patients with Cluster B diagnosis.

Age-related differences in the use of guideline-recommended medical and interventional therapies for acute coronary syndromes: a cohort study

To compare the use of guideline-recommended medical and interventional therapies in older and younger patients with acute coronary syndromes (ACSs).