Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS).

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.     

Dose-response study of somatostatin on meal-stimulated levels of pancreatic polypeptide and insulin in the dog

A dose-response study of the effect of 0.1-5.0 micrograms kg-1 h-1 somatostatin was performed on food-induced rise of pancreatic polypeptide and insulin in 4 dogs. There was a dose-dependent suppression of the release of pancreatic polypeptide and insulin with an ED50 of approximately 0.65 and 0.8 microgram kg-1 h-1, respectively, during the first 45-min period. In the second 45-min period, high doses of somatostatin failed to suppress insulin concentrations whereas, the serum concentrations of pancreatic polypeptide were reduced by a similar degree as in the first 45 min. The differing effects of somatostatin on food-stimulated serum concentrations of insulin and pancreatic polypeptide indicate that somatostatin does not represent a uniform suppressor of pancreatic hormones.     

The challenge of individualised risk assessment and therapy planning in elderly high-risk myelodysplastic syndromes (MDS) patients

Myelodysplastic syndromes (MDS) represent one of the most frequent and serious haematologic diseases of the elderly. Effective therapies exist ranging from best supportive care to haematologic stem cell transplantation (HSCT). Decision making, however, is rather complex in this group of patients because ageing is a multidimensional process involving not only physiological changes but also changes in functional, social, emotional and cognitive capacities. All these factors can have a significant impact on the efficacy and tolerability of a potential therapy and therefore have to be thoroughly assessed before deciding on individual treatment regimens. Risk assessment tools are available both to classify the stage and prognosis of MDS and to meet the needs of elderly patients. A tool explicitly focussing on elderly MDS patients, however, is still missing. The current report approached this issue by combining the well established MDS-risk score 'International Prognostic Scoring System' (IPSS) with the 'Multidimensional Geriatric Assessment' (MGA). As decision making is most complex in high-risk MDS patients, the new algorithm is presented exemplarily for this group of patients. In a first step, MDS-related risk is identified using IPSS, in a second step, patients are assigned to one of three risk categories of the MGA (go-go/fit, slow-go/vulnerable, no-go/frail). While go-go patients might be subjected to therapies comparable to those given to younger patients, in no-go patients, a palliative therapy combined with best supportive care will probably be most appropriate. In slow-go patients, age-related life expectancy taken from public age statistics should be compared to the MDS-related life expectancy. Based on this combined assessment procedure and also on treatment tolerance in terms of the expectations/wishes of the patient and his/her family, an individualised therapeutic approach should be developed. Specific treatment recommendations for these three groups of patients are given, including HSCT, azanucleosides and best supportive care. To illustrate its practicability, i.e. the implementation of the novel algorithm in clinical practice, the case of an elderly high-risk MDS patient is presented and discussed in detail. This new algorithm will facilitate the identification of the very particular needs and conditions of elderly MDS patients in clinical practice. Based on this, individually tailored therapeutic approaches can be developed--the prerequisite for the best possible clinical outcome.     

Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n?=?302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20–30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53–10.7)?months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.     

Coronary artery bypass grafts: assessment of graft patency and native coronary artery lesions using 16-slice MDCT

The objective of this study was to evaluate the accuracy of electrocardiography (ECG)-gated 16-slice multidetector-row computed tomography (MDCT) in detection of stenosis of bypass grafts and native coronary arteries in patients who have undergone coronary artery bypass grafting (CABG). ECG-gated contrast-enhanced MDCT using 12×0.75-mm collimation was performed in 20 patients with recurrent angina 4.75 years after undergoing CABG. A total of 50 grafts, 16 arterial and 34 venous, were examined. All graft and coronary segments were evaluated for stenosis in comparison with conventional coronary angiography (CCA). Among the 80 arterial graft segments, 62 could be assessed (77.5%). Sensitivity, specificity, and positive and negative predictive values for stenosis were 96.2%, 97.2%, 96.2%, and 97.2%, respectively. In a total of 180 venous graft segments, 167 could be assessed. Sensitivity, specificity, and positive and negative predictive values for stenosis were 98.5%, 93.9%, 91.8%, and 98.9%, respectively. MDCT could assess 179 of 260 native coronary artery segments (68.8%).Sensitivity, specificity, and positive and negative predictive values for stenosis were 92.1%, 76.9%, 87.5%, and 84.7%, respectively. Sixteen-slice MDCT provides excellent image quality and diagnostic accuracy in detection of graft and coronary artery lesions in patients with suspected graft dysfunction.     

Severity of allergic complaints: the importance of depressed mood

Objective: To evaluate the prevalence of depressive symptoms in patients with different kinds of allergic diseases and the connection of depressive symptoms with the severity, type and seasonality of allergic complaints. Methods: Data was obtained via a cross-sectional multicenter questionnaire survey of 528 patients aged 16–60 years attending six regional in- and outpatient allergy clinics in Hungary in June to July 1998. Consecutive patients completed a structured, self-administered questionnaire containing questions about their current and past allergic complaints. Depressive symptoms were measured by the Shortened Beck Depression Inventory (BDI). Results: 32.2% of patients scored above the normal level (≥10) and 12.5% had clinically significant depressive symptomatology (≥19) by the BDI. These rates were significantly higher than those found in the control group from a national representative population sample (22.4% and 8.3%). Patients with asthma and with perennial symptoms had significantly higher depression scores than patients with other types of allergic diseases. There was a significant association between the severity of depressive symptoms and the severity of allergic complaints independently from age, sex, type and seasonality of the allergic disease, and other current physical illnesses and symptoms tested by the General Linear Model (GLM). Conclusions: Our results draw attention that patients even with mild depressive symptoms have significantly more severe allergic complaints and assess general health state as much worse than those without depressive symptoms in any types of allergic diseases. Diagnosis and treatment of depressive symptoms in allergic patients is of great concern from both a clinical and an economical point of view.     

Perceptual processing among high-functioning persons with autism

Two tasks were used to assess the processing of whole versus parts of objects in a group of high-functioning children and adolescents with autism (N = 11) and a comparison group of typically developing peers (N = 11) matched for chronological age and IQ. In the first task, only the children with autism showed a global advantage, and the two groups showed similar interference between levels. In the second task, the children with autism, despite longer RTs, showed similar performance to the comparison group with regard to the effect of goodness on visual parsing. Contrary to expectations based on the central coherence and hierarchisation deficit theories, these findings indicate intact holistic processing among persons with autism. The implications of these findings are discussed in relation to apparently discrepant evidence from other studies.