Impact of anaemia on health-related quality of life and cardiac remodelling in patients with lower risk myelodysplastic syndromes. Results of GlobQoL study.

The aim of this study was to analyse the eventual changes in health-related quality of life (HRQoL) and left ventricular function (LVF) over a 1-year follow-up period in a cohort of patients with lower risk myelodysplastic syndromes (MDS) receiving standard supportive treatment, in order to identify potential clues for early clinical intervention, as well as to analyse how they relate to haemoglobin levels and other aspects of the disease. A total of 39 adult anaemic patients with lower risk MDS were included in a prospective, observational, multi-centre study. Changes in performance status, functional capacity and HRQoL were collected by using standardised measures (ECOG scale; SPPB, Short Physical Performance Battery; SF-36, Short-Form 36 questionnaire; QLQ-C30, Quality of Life Core Questionnaire; FACT-An, Functional Assessment of Cancer Therapy-Anaemia scale questionnaires respectively). Need for transfusion (Linear Analogue Scale Assessment), as perceived independently by the patient and the haematologist, was also recorded. No changes in HRQoL (or LVF) were found, except for slight reductions in SF-36 physical function (P = 0.034), SPPB gait speed (P = 0.038) and FACT-An score (P = 0.029), all without apparent immediate clinical relevance for HRQoL, that were unrelated to changes in haemoglobin level. Periodical evaluation of gait speed may assist the clinician in early detection of patient's occult functional decline before it becomes clinically relevant.

Real-world cost-effectiveness of infliximab, etanercept and adalimumab in rheumatoid arthritis patients: results of the CREATE registry.

Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038­84,076), €87,040 (78,496­95,584) and €102,683 (94,559­110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.

Cost-effectiveness of clinical remission by treat to target strategy in established rheumatoid arthritis: results of the CREATE registry.

To analyse the cost-effectiveness, in daily clinical practice, of the strategy of treating to the target of clinical remission (CR) in patients with established rheumatoid arthritis (RA), after 2 years of treatment with biological therapy. Adult patients with established RA were treated with biological therapy and followed up for 2 years by a multidisciplinary team responsible for their clinical management. Treatment effectiveness was evaluated by the DAS28 score. The direct costs incurred during this period were quantified from the perspective of the healthcare system. We calculated the cost-effectiveness of obtaining a DAS28 < 2.6, considered as CR. The study included 144 RA patients treated with biological therapies. After 2 years of treatment, 32.6% of patients achieved CR. The mean cost of achieving CR at 2 years was 79,681 ± 38,880 euros. The strategy of treatment to the target of CR is considered the most effective, but in actual clinical practice in patients with established RA, it has a high cost.

Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification.

Morphology is the basis of the diagnosis of myelodysplastic syndromes (MDS). The WHO classification offers prognostic information and helps with the treatment decisions. However, morphological changes are subject to potential inter-observer variance. The aim of our study was to explore the reliability of the 2008 WHO classification of MDS, reviewing 100 samples previously diagnosed with MDS using the 2001 WHO criteria. Specimens were collected from 10 hospitals and were evaluated by 10 morphologists, working in five pairs. Each observer evaluated 20 samples, and each sample was analyzed independently by two morphologists. The second observer was blinded to the clinical and laboratory data, except for the peripheral blood (PB) counts. Nineteen cases were considered as unclassified MDS (MDS-U) by the 2001 WHO classification, but only three remained as MDS-U by the 2008 WHO proposal. Discordance was observed in 26 of the 95 samples considered suitable (27 %). Although there were a high number of observers taking part, the rate of discordance was quite similar among the five pairs. The inter-observer concordance was very good regarding refractory anemia with excess blasts type 1 (RAEB-1) (10 of 12 cases, 84 %), RAEB-2 (nine of 10 cases, 90 %), and also good regarding refractory cytopenia with multilineage dysplasia (37 of 50 cases, 74 %). However, the categories with unilineage dysplasia were not reproducible in most of the cases. The rate of concordance with refractory cytopenia with unilineage dysplasia was 40 % (two of five cases) and 25 % with RA with ring sideroblasts (two of eight). Our results show that the 2008 WHO classification gives a more accurate stratification of MDS but also illustrates the difficulty in diagnosing MDS with unilineage dysplasia.

Fibromyalgia in patients with ankylosing spondylitis: prevalence and utility of the measures of activity, function and radiological damage.

OBJECTIVES: To determine the prevalence of fibromyalgia (FM) in ankylosing spondylitis (AS). To evaluate the effect of FM on the measures of activity in AS. To analyse predictive factors in order to identify this group of patients. PATIENTS AND METHODS: A cross-sectional study based on 462 patients with definite ankylosing spondylitis included in the REGISPONSER. Sociodemographic data, clinical features, Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS radiology index (BASRI), Stoke modified index (Sasss-m), laboratory data, Short-Format 12 (SF-12), AS specific quality of life (ASQoL), Fibromyalgia Impact Questionnaire (FIQ) and treatments used were all documented. To diagnose FM, the ACR 1990 criteria had to be fulfilled. All statistical tests were performed using STATA. RESULTS: The prevalence of fibromyalgia in all AS was 4.11%. Among the women with AS, the prevalence of FM increased to 10.83%. The BASDAI, BASFI and total BASRI were strongly influenced by the presence of FM. The inverse relationship between BASDAI or BASFI and total BASRI was taken to generate a ratio. Accordingly, if the patient presented BASDAI/BASRI ≥1.5 or BASFI/BASRI ≥1.08, the probability of having FM was very high. CONCLUSIONS: There is an increased risk of FM in females with AS. The fact of having FM distorts the measures of activity and functional damage of AS. As a result, it is possible that some patients with AS and FM are being overtreated. The BASDAI/BASRI and BASFI/BASRI ratios are very useful to identify these patients.

Evaluation of CD7 and terminal deoxynucleotidyl transferase (TdT) expression in CD34+ myeloblasts from patients with myelodysplastic syndrome.

There is an emerging use of flow cytometry to evaluate patients with myelodysplastic syndrome (MDS). We have studied CD7 and TdT expression in the CD34+ myeloid blast cell population in 55 bone marrow samples of patients with MDS. CD7 and/or TdT were detected in 38 out of 55 patients (69%). CD7 expression was not related to other bad prognosis data but conversely, we found an association between TdT+ CD34 myeloblasts and high-risk MDS patients according to the International Prognostic Scoring System. Therefore, CD7 and TdT may help to establish the diagnosis of MDS and, TdT expression also seems to be a useful marker in distinguishing risk groups.

Plasma endothelin-1 levels after stem cell transplantation.

Acute renal failure and veno-occlusive disease of the liver are serious complications following stem cell transplantation (SCT) and contribute to the non-relapse mortality associated with this procedure. Endothelins, a family of vasoconstrictor peptides, may be involved in the pathogenesis of a variety of renal and hepatic diseases, including CsA-associated hypertension and the hepatorenal syndrome. In order to study the relevance of endothelins to SCT-related liver and kidney dysfunction, we determined endothelin-1 (ET-1) levels in plasma samples obtained from 65 patients (38 autologous, 27 allogeneic) 7 days before and 7, 14 and 28 days after SCT. A steady increase in plasma ET-1 was observed after SCT (5.36 pg/ml, 95% CI 4.30-6.43 on day +28 vs 3.82 pg/ml, 95% CI 3.21-4.43 on day -7; P = 0.020). No differences in ET-1 levels existed between autologous and allogeneic SCT recipients at any of the time points studied (P = 0.561). In addition, no significant differences were observed among patients with renal dysfunction vs those without (P = 0.187), nor in patient groups with or without hepatic dysfunction (P = 0.075). In conclusion, even though plasma ET-1 levels showed a steady increase following SCT, no correlation could be found with development of SCT-related kidney or liver dysfunction.

The quotient of number of nodes and tumour size (N/T) from primary breast cancer predicts the clinical course after diagnosis of distant relapse.

INTRODUCTION: Breast cancer is a disease with a very variable progression. Primary tumour size and metastatic lymph node involvement are the best indicators of the likelihood of relapse. However, their value in predicting progression following relapse is not clear. AIM: The aim of this study was to asses whether the relationship between tumour size and the number of lymph nodes involved had any value as predictive factors of post-relapse progression. METHOD: We established an index defined as the quotient between the number of diseased lymph nodes and the tumour size (in cm). RESULTS: Applying this index in 230 consecutive patients with metastatic breast cancer, we observed that there was a significant inverse relation between the index and post-relapse progression. CONCLUSION: We conclude that, at the time of initial diagnosis, the quotient of tumour size and the number of diseased lymph nodes could be a good predictor of time-to-progression following the diagnosis of the metastatic disease.

Diagnostic interest of the monoclonal antibody CA1 in malignant pleural effusion.

The Ca1 antibody was used in an immunohistochemical procedure on smears of cells from 40 patients with malignant pleural effusion. The control group consisted of 25 benign pleural effusions with a high percentage of reactive mesothelial cells. The Ca1 Mc Ab was positive in 19 (79%) of the 24 pleural effusions with positive malignant cytology. In all the benign cases the Ca1 Mc Ab was negative (100% specificity). The Ca1 Mc Ab detected malignant mesothelial cells in two cases and was negative with reactive mesothelial cells and other nucleated cells present in the pleural effusion. We conclude that the Ca1 antibody offers a useful diagnostic method for malignant pleural effusions, when the morphological interpretation is doubtful.

[Comparative study of piperacillin/tazobactam versus imipenem/cilastatin in febrile neutropenia (1994-1996)]. / Estudio comparativo de piperacilina/tazobactam frente a imipenem/cilastatina en la neutropenia febril (1994-1996).

BACKGROUND: We aimed at comparing the effectiveness and safety of piperacillin/tazobactam(PIP-TAZ) versus imipenem/cilastin (IMI) administered as empiric monotherapy in patients with febrile neutropenia. PATIENTS AND METHOD: Patients with hematological diseases who were randomly assigned either PIP-TAZor IMI were enrolled in the study. A sequential strategy of antibiotic therapy addition was applied as long as fever persisted or microorganisms were isolated at 72 h. Moreover, if bacteriologically unconfirmed fever persisted after 5-7 days, an antifungal therapy was started. The treatment was considered successful if fever and clinical signs resolved and/or pathogens were cleared without adding further antibiotics at 72 h. Differences between percentages were analyzed using the *2test. RESULTS: 137 patients were evaluated. The successful response rate of PIP-TAZ after 72 h was similar to IMI (32.2 and 35.2%). The defervescence time was shorter (3.6 and 4.2 days) and the bacterial response more favourable with PIP-TAZ than with IMI, but statistically significant differences were not reached. The overall response in both groups was 91%.18.2% of episodes were bacteriologically confirmed. The most frequent isolated microorganism was Staphylococcus coagulase-negative(48.8%). There was one only case of septic shock, within the IMI group, and the overall mortality of the group was 8.7%. The occurrence of vomiting in the IMI group was significantly higher than in the PIP-TAZ group (39.9 and 5.6%; p < 0.0001). CONCLUSIONS: PIP-TAZ is as effective as IMI and it constitutes a good choice as an initial empiric monotherapy of febrile neutropenia.

[Bladder amyloidosis: report of 2 cases]. / Amiloidosis vesical: presentación de dos casos.

Two cases of amyloidosis of the bladder are reported: 1) a 45 year old man with haematuria. Cystoscopic examination reveals several tumours in the wall of the bladder. Transuretral resection was performed and histopathological examination revealed primary amyloidosis. Systemic amyloidosis was excluded. He was treated with oral colchicine with success. 2) a 71 year old male with diagnosis of rheumatoid arthritis and systemic amyloidosis visited our hospital with massive haematuria. Transuretral resection was unsuccessful and was necessary surgical ligation of hypogastric arteries.

[Epidermoid cysts of the testis]. / Quistes epidermoides de teste.

The epidermoid cyst of the penis is an uncommon benign intratesticular tumour. This paper presents two cases that were diagnosed and operated in our centre. It also describes the most significant clinical, radiological and histological aspects.

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.

Cryptic Leishmaniosis by Leishmania infantum, a feature of canines only? A study of natural infection in wild rabbits, humans and dogs in southeastern Spain.

An epidemiological study was carried out to investigate asymptomatic Leishmania infantum infection by PCR and ELISA in wild rabbits, humans and domestic dogs in southeastern Spain. Seroprevalence was 0% (0/36) in rabbits, 2% (13/657) in humans and 7% (14/208) in dogs. The prevalence of PCR-positives was 0.6% (1/162) in rabbits tested in a wide range of tissue samples, 2% (8/392) in humans analysed in blood samples and 10% (20/193) and 67% (29/43) in dogs analysed in blood and lymphoid tissue samples, respectively. Results suggest that wild rabbits have a very low risk of becoming chronically infected with L. infantum, and provide further evidence that cryptic L. infantum infection is widespread in the domestic dog population and is also present in a comparatively smaller proportion of healthy humans. The epidemiological and clinical implications of these findings are discussed.

Geographical variation and factors associated to seroprevalence of canine leishmaniosis in an endemic Mediterranean area.

This article retrospectively analyses the spatial distribution and dog- and environmental-level risk factors associated to Leishmania infantum seroprevalence among 807 asymptomatic dogs in the Municipality of Crevillente in Alicante in southeast Spain in 1999. They represented 60% of the dogs in this 103 km2 area, with a human census of 27 034 people and 90% lived in Crevillente town. The estimated seroprevalence (95% confidence interval) in 714 dogs > or =1-year old was 22% (19-25) however; it was 12% (8-15) in town dogs and 0-100% in other administrative zones. High-medium seroprevalence zone clustered along a northeast-southwest fringe and around the town. They comprised the highest and driest inhabited part of the municipality, where farmland was interspersed by residential detached houses, whilst null-low seroprevalence zones included larger farmland extensions and two small rural villages. Predominant vegetation and ground soil type were bush, non-irrigated fruit trees and conglomerate crust and sandstone in medium-high seroprevalence zones and irrigated grassland and fruit trees and colluvial deposits in null-low seroprevalence zones. Random effects logistic regression indicated that the prevalence of infection with L. infantum was higher for dogs sharing residence with infected dogs, increased until 5-6 years old and with body weight and was associated to increasing conglomerate crust and low surface water in the dog's zone of residence. The study confirms that L. infantum infection is endemic in this part of Spain and shows that prevalence can vary significantly within a small area depending on specific demographic and environmental factors conditioning the habitat of the local L. infantum vector, Phlebotomus perniciosus. It suggests similar low-scale variability is present in other geographically variable endemic areas and should be investigated to design Leishmaniosis risk maps and cost-effective, evidence-based, targeted control interventions.

Persistent polyclonal B lymphocytosis with multiple bcl-2/IgH rearrangements: a benign disorder.

The appearance of a chronic B lymphocytosis is usually associated with the existence of an underlying monoclonal malignant condition. However, a few cases of persistent polyclonal B cell lymphocytosis (PPBL), presented in young asymptomatic women with an uneventful course, have been reported in recent years. In these PPBL cases, since the lymphocytes usually display an anomalous morphology, a false diagnosis of a neoplastic chronic lymphoproliferative syndrome can be easily made. We report a typical case of PPBL that presents multiple bcl-2 rearrangements, the typical finding of follicular lymphomas. A review of different causes of benign non neoplastic lymphocytosis with special steadiness in changes in the lymphoid subsets will be made.