Variables related to chronic immune thrombocytopenia: experience from a single center and comparison to a meta-analysis.

Classically, several variables have been related to the disease course of chronic primary immune thrombocytopenia (cITP), though to date, there is no consensus on their clinical relevance. In a recent systematic review, a meta-analysis was made and confirmed the existence of certain cITP-related variables that may be related to prognosis in pediatric patients. We retrospectively analyzed a cohort of patients diagnosed with ITP, identified prognostic variables, and compared our results to the variables described by the authors. A multivariate study revealed that older age at diagnosis and higher platelet count were the only independent variables related to cITP. Children up to age 4 years and those with lower platelet counts (below 20 × 109/L) were at lower risk for cITP.Conclusion: We therefore concluded that only age and platelet count at diagnosis are independent variables that should be considered when evaluating the risk of developing cITP. What is Known: • Around 20% of patients with immune thrombocytopenia progress to chronic disease as determined by a sustained platelet count below 100×109/L for more than 12 months. • A number of variables potentially related to the development of cITP are being studied, such as age, sex, cell count, and previous treatment. What is New: • This is a new group of patients diagnosed with ITP in which the platelet count and age at diagnosis are the only independent variables closely related to cITP. • In this new series, we could not confirm other variables previously related to cITP such as total leukocyte count or the absence of treatment at diagnosis.

Venous thromboembolism in patients with liver diseases.

Essentials Emerging evidence shows that patients with liver disease are not protected from thrombotic events. We assessed the risk of venous thromboembolism (VTE) in patients with liver disease. The presence of VTE resulted in an increase in mortality for patients with liver disease. Hospitalized patients with moderate-severe liver disease had low risk of VTE during admission. SUMMARY: Background and Aims Patients with liver disease were traditionally believed to be protected against development of blood clots, but some studies have shown a potential increased risk of venous thrombotic complications. We assessed the risk of venous thromboembolism (VTE) in patients with liver disease. Methods Data in discharge reports of patients with liver disease and control patients without liver disease were analyzed from the national inpatient sample. Incidence of VTE was compared in patients with mild, moderate-severe or no liver disease, and the impact on in-hospital mortality and length of stay was calculated. Results The overall incidence of VTE for patients with no liver disease, mild liver disease and moderate-severe liver disease was 2.7, 2.4 and 0.9 per 100 patient discharges, respectively. In the presence of VTE, in-hospital mortality was 10.8%, 5.8%, and 21.7% for the no liver disease, mild disease and moderate-severe liver disease, respectively. The presence of VTE resulted in an increase in mortality for patients with no liver disease (OR, 1.16; 95% CI, 1.14-1.18) and moderate-severe liver disease (OR, 1.63; CI 95%, 1.42-1.88). Conclusions Patients with moderate-severe liver disease have a lower risk of VTE than those without liver disease. Development of thrombosis during admission increased the risk of in-hospital mortality.

Pri sORF peptides induce selective proteasome-mediated protein processing.

A wide variety of RNAs encode small open-reading-frame (smORF/sORF) peptides, but their functions are largely unknown. Here, we show that Drosophila polished-rice (pri) sORF peptides trigger proteasome-mediated protein processing, converting the Shavenbaby (Svb) transcription repressor into a shorter activator. A genome-wide RNA interference screen identifies an E2-E3 ubiquitin-conjugating complex, UbcD6-Ubr3, which targets Svb to the proteasome in a pri-dependent manner. Upon interaction with Ubr3, Pri peptides promote the binding of Ubr3 to Svb. Ubr3 can then ubiquitinate the Svb N terminus, which is degraded by the proteasome. The C-terminal domains protect Svb from complete degradation and ensure appropriate processing. Our data show that Pri peptides control selectivity of Ubr3 binding, which suggests that the family of sORF peptides may contain an extended repertoire of protein regulators.

Depressive symptoms are independently associated with pain perception in Colombians with rheumatoid arthritis.

AIMS: To examine the relationships between psychosocial factors and reported pain in Colombians with Rheumatoid Arthritis (RA). METHODS: One hundred and three RA patients [85% from the lowest socio-economic strata (SES) in the country] recruited from outpatient centers in Neiva, Colombia were administered the Disease Activity Scale (DAS) , which included a Visual Analog Scale (VAS) arthritis pain/activity rating, Zung Depression Scale, State-Trait Anxiety Inventory (STAI), Interpersonal Support Evaluation List-12 (ISEL-12), and Symptom Checklist-90 Revised (SCL-90R). MAJOR RESULTS: VAS pain was not associated with socio-demographic or medical factors, but was negatively associated with ISEL tangible subscale (r=-0.22, p< 0.01; r=0.28, p<0.01). VAS pain was positively associated with Zung Depression Scale score (r=0.38, p<0.001), STAI-State and STAI-Trait Anxiety (r=0.23 and r=0.25 respectively, p's<0.01), SCL-90R Global Severity Index (GSI) and Positive Symptom Total (PST) (r=0.23, p<0.05 and r=0.29, p<0.01 respectively), and SCL-90R Somatization, Depression, and Anxiety subscales (r=0.30, p< 0.01; r=0.28, p<0.01; and r=0.20, p<0.05 respectively). A linear regression model showed that socio-demographic characteristics theoretically associated with pain perception (gender, age, and SES) explained only 2.4% of the variance of VAS scores (R(2)=0.02, p=0.49). The full model, including psychosocial factors significantly associated with VAS scores explained 18.9% of the variance in VAS pain perception scores (R(2)=0.19, p=0.02). The Zung Depression Scale score was the only factor independently associated with VAS pain, such that higher depression scores were associated with higher VAS ratings (ß =0.13, p<0.01), controlling for gender, age, SES, STAI-State, STAI-Trait, ISEL tangible, SCL-90R GSI, and SCL-90R PST. CONCLUSIONS: Depressive symptoms, anxiety, social support, and psychopathological symptom distress were associated with pain ratings, but only depressive symptoms were found to be uniquely associated with higher pain perception, taking into account socio-demographic characteristics and other psychosocial factors. Findings provide evidence for the need to assess and treat pain in RA in Colombia from a bio-psycho-social perspective. Future research is needed to determine effective depression screening and evidence-based interventions for depressive symptoms in RA patients in this socio-cultural context, as intervening in depression may decrease pain perception.

Malnutrition and obesity: influence in mortality and readmissions in chronic obstructive pulmonary disease patients.

BACKGROUND: The present study aimed to assess the association of obesity and malnutrition with the mortality of hospitalised patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and the risk of readmission in <30 days. METHODS: A retrospective chart review of consecutive patients admitted with COPD as the primary reason for discharge in Spain between 1 January 2006 and 31 December 2007 was performed. Patients with a diagnosis of obesity or malnutrition in the hospital discharge clinical report were identified. The in-hospital mortality and re-admittance 30 days after discharge indices of obese and malnourished patients were compared against the subpopulation without these diagnoses. RESULTS: Of the 313 233 COPD admittances analysed, there were 22 582 (7.2%) diagnoses of obesity and 6354 (2.0%) diagnoses of malnutrition. In-hospital global mortality and the re-admittance risk were 12.0% and 16.7%, respectively. Obese patients showed a lower in-hospital mortality risk [odds ratio (OR) = 0.52; 95% confidence interval (CI) = 0.49-0.55] and early re-admittance risk (OR = 0.87; 95% CI = 0.85-0.92) compared to non-obese patients. Malnourished patients had a much higher risk of death when in hospital (OR = 1.73; 95% CI = 1.62-1.85) or of being re-admitted within 30 days after discharge (OR = 1.29; 95% CI = 1.22-1.38), even after adjusting for possible confounding factors. CONCLUSIONS: Obesity in patients hospitalised for COPD substantially reduces in-hospital mortality risk and the possibility of early re-admittance. Malnutrition is associated with an important increase in in-hospital mortality and risk of re-admittance in the 30 days following discharge.

Bronchopulmonary complications associated to enteral nutrition devices in patients admitted to internal medicine departments.

BACKGROUND AND AIMS: Enteral nutrition using feeding devices such as nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) is an effective feeding method subject that may give rise to complications. We have studied the relationship between enteral nutrition feeding devices in patients admitted to the Internal Medicine Departments and the development of pulmonary complications (bronchial aspiration and aspiration pneumonia). PATIENTS AND METHODS: All of the patients discharge between 2005 and 2009 from the Internal Medicine (IM) Departments of the public hospitals of the National Health System in Spain were analyzed. The data of patients with bronchial aspiration or aspiration pneumonia who also were carriers of NG tubes or PEG, were obtained from the Minimum Basic Data Set (MBDS). RESULTS: From a total of 2,767,259 discharges, 26,066 (0.92%) patients with nasogastric tube (NG tube) or percutaneous gastrostomy (PEG) were identified. A total of 21.5% of patients with NG tube and 25.9% of patients with PEG had coding for a bronchopulmonary aspiration on their discharge report versus 1.2% of patients without an enteral feeding tube. In the multivariate analysis, the likelihood of suffering bronchoaspiration was 9 times greater in patients with SNG (OR: 9.1; 95% CI: 8.7-9.4) and 15 greater in subjects with PEG (OR: 15.2; 95% CI: 14.5-15.9) than in subjects without SNG or PEG. Mean stay (9.2 and 12.7 more days), diagnostic complexity and costs were much higher in patients with SNG or PEG compared to patients in hospital who did not require these devices. CONCLUSIONS: An association was found between SNG and PEG for enteral feeding and pulmonary complications. Mean stay, diagnostic complexity and cost per admission of these patients was higher in patients who did not require enteral nutrition.

[Invasive procedures in patients hospitalized in Spanish internal medicine departments]. / Procedimientos invasivos en pacientes ingresados en los servicios de Medicina Interna españoles.

AIMS: Invasive procedures (IP) have become routine techniques that benefit an important number of patients on improving their quality of life or avoiding more aggressive treatments. We have conducted a study on the IPs performed in Spanish Internal Medicine (IM) Departments between 2005 and 2009. PATIENTS AND METHODS: IP performed to patients admitted to Spanish Internal Medicine departments were analyzed based on the information obtained from the Minimum Basis Data Set (CMBD). IP was defined as the following: filter placement in the inferior vena cava, chest tube placement, biliary, esophageal and colon prosthesis placement, pleurodesis, nephrostomy, external biliary drain placement, gastrostomy tube placement, thoracocentesis and peritoneal catheter placement. RESULTS: During the study period, a total of 75,853 invasive procedures on 70,239 admittances were performed in 2,766,673 patients (2.5%). IP subjects were younger (68.1 vs 71.4; P<.001), predominantly male (61.9 vs 53.2%; P<.001), with higher mortality (14.6 vs 9.9%; P<.001) and longer stay (18.4 vs 9.6 days; P<0.001). Cost of admittance was clearly higher than the rest of the patients (5,600€ vs 3,835€; P<.001). CONCLUSIONS: IPs are performed on a low percentage of IM Department hospitalized patients. They are costly, entail high mortality and a longer stay period compared to the mean population admitted to IM. A considerable proportion of the patients receiving IP suffer from neoplastic diseases, frequently in advances stages, which justifies the high inhospital mortality of this population.

The indication of tracheotomy conditions the predictors of time to decannulation in critical patients.

OBJECTIVE: Variables predicting optimal timing for tracheostomy decannulation remain unknown. We aimed to determine whether classifying patients into two groups according to their indications for tracheostomy could identify variables associated with time to decannulation. DESIGN: A prospective, observational cohort study was carried out. LOCATION: Two medical-surgical ICUs. PATIENTS: We included all patients tracheostomized during ICU stay, excluding patients with do-not-resuscitate orders, tracheostomies for long-term airway control, neuromuscular disease, or neurological damage. Patients were classified into two groups: patients tracheostomized due to prolonged weaning and/or prolonged mechanical ventilation (Group 1), and patients tracheostomized due to low level of consciousness or inability to manage secretions (Group 2). INTERVENTIONS: Patients were weaned and decannulated according to established protocols. MAIN VARIABLES: We recorded the following variables: time to tracheostomy, forced vital capacity, peak flow, suctioning requirements, Glasgow Coma Score (GCS), characteristics of respiratory secretions, and swallowing function. Statistical analyses included Cox-proportional multivariate analysis with time to decannulation as the dependent variable. RESULTS: A total of 227 patients were tracheostomized in the ICUs; of these, 151 were finally included in the study. In the multivariate analysis, time to decannulation in Group 1 was associated with the male gender (HR 1.74 (1.04-2.89), p= 0.03), age>60 years (HR 0.58 (0.36-0.91), p= 0.02), high suctioning frequency (HR 0.81 (0.67-0.97), p= 0.02), low forced vital capacity (HR 0.48 (0.28-0.82), p<0.01), and low peak flow (HR 0.25 (0.14-0.46), p<0.01). In Group 2 time to decannulation was associated to GCS >13 (HR 2.73 (1.51-4.91), p<0.01), high suctioning frequency (HR 0.7 (0.54-0.91), p<0.01), and inadequate swallowing (HR 1.97 (1.11-3.52), p=0.02). CONCLUSION: Variables associated with longer time to decannulation in ICU-tracheostomized patients differ with the indications for tracheostomy.

The impact of weekends on outcome for acute exacerbations of COPD.

Differences in hospital staffing may influence outcomes for patients with acute conditions, including acute exacerbations of chronic obstructive pulmonary disease (COPD), depending on which day of the week the patients are admitted. This study was conducted to determine whether weekend admission increases the risk of dying in hospital. We analysed the clinical data of 289,077 adults with acute exacerbations of COPD admitted to the hospital at any public centre in Spain, during 2006 and 2007. We analysed the following factors for their association with death rate: day of admission, demographics, medical history and comorbidity. During the study period, there were 35,544 (12.4%) deaths during admission in COPD patients. Weekend admissions were associated with a significantly higher in-hospital mortality (12.9%) than weekday admissions (12.1%) among COPD patients (OR 1.07 (95% CI 1.04-1.10)). The differences in mortality persisted after adjustment for age, sex and coexisting disorders (OR 1.05 (95% CI 1.02-1.08)). Analyses of deaths within 2 days after admission showed larger relative differences in mortality between the weekend and weekday admissions (OR 1.17 (95% CI 1.11-1.23)). We conclude that patients with acute exacerbations of COPD are more likely to die in the hospital if they are admitted on a weekend compared with a weekday.

[Survey of Spanish Society of Internal Medicine on health care provision by internists in the public health system]. / Encuesta SEMI sobre la oferta asistencial de los internistas en los hospitales del Sistema Público de Salud.

AIMS: To know the organization of internal medicine departments (IMD) and the opinion of their heads of department. METHODS: In 2008, a survey was mailed to 410 heads of department of the IMD of 313 Spanish public hospitals. It included a standardized structured questionnaire on staff, hospitalization, outpatients, consultation, research and teaching. The heads of departments were also asked for their opinion and suggestions on management, projects and future. RESULTS: Sixty-eight surveys (22%) were filled out. Internists are on call an average of 3 times a month and perform 200 discharges, 500 outpatient visits and 40 consultations in a year. The average IMD consists of 10 internists with one-fifth of the hospital beds. One third of hospitals have alternatives to inpatient care, the most frequent being palliative care. Infectious diseases accounts for the most common monographic outpatient visit, one-third of IMD lack a structured relationship with primary care and the emergency department is independent of IMD. Half of the IMD have at least one IM resident and 6 residents in other specialties; half are involved in at least two clinical trials and one-third train medical students. The heads of the IMD identify problems in their relationship with hospital managers, other specialties and local population. Excessive workload, aging and discouragement of staff and patients' social problems have negative effects. Even so, they want to initiate projects, are optimistic about the future and take an interest in clinical epidemiology research. CONCLUSIONS: Although the sample is small and heterogeneous, it permits a valuable panoramic view of the structure and standard operation of a Spanish IMD as well as their expectations and areas of improvement.

Small peptides switch the transcriptional activity of Shavenbaby during Drosophila embryogenesis.

A substantial proportion of eukaryotic transcripts are considered to be noncoding RNAs because they contain only short open reading frames (sORFs). Recent findings suggest, however, that some sORFs encode small bioactive peptides. Here, we show that peptides of 11 to 32 amino acids encoded by the polished rice (pri) sORF gene control epidermal differentiation in Drosophila by modifying the transcription factor Shavenbaby (Svb). Pri peptides trigger the amino-terminal truncation of the Svb protein, which converts Svb from a repressor to an activator. Our results demonstrate that during Drosophila embryogenesis, Pri sORF peptides provide a strict temporal control to the transcriptional program of epidermal morphogenesis.

Possible association between NOD2 variants and joint surgery in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) has been inconsistently associated with common NOD2 gene variants, although some of these studies did not include patient stratification by clinical phenotype. OBJECTIVES: To analyse the association between the three common NOD2 variants (R702W, G908R and L1007fs) and clinical phenotypes of PsA, particularly with surrogate markers of severe joint destruction. PATIENTS AND METHODS: A total of 183 unrelated PsA patients and 187 controls were included. Demographic, clinical, biological and immunological characteristics were collected. Genotypes for the three common NOD2 gene variants were obtained by PCR and direct sequencing. RESULTS: NOD2 variants in PsA patients (7.6%) are just as prevalent as in healthy controls (7.5%). 18.5% of PsA patients carrying at least one NOD2 variant underwent joint surgery compared with 4.5% of those without these variants (p=0.019). Multivariate analysis confirmed this finding (OR 8.82, CI 1.7-46.3). There was no requirement for early surgery in patients carrying the NOD2 variants but there was an increased possibility of requiring surgery at similar times of disease duration. No other association with clinical features and NOD2 status carrier was found. CONCLUSIONS: Common NOD2 gene variants are not associated with PsA, but might increase the risk of undergoing joint replacement surgery, suggesting that this autoinflammatory-associated gene could act as a phenotypic modifier gene in PsA patients by increasing the risk of joint destruction. Given the small number of PsA patients with joint surgery included, we consider our findings a new hypothesis that will need further testing.

KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer.

The let-7 family of microRNAs are important regulatory molecules in lung cancer. One downstream target of let-7 is the RAS gene family, including KRAS, an important oncogene in the etiology and clinical outcome of lung adenocarcinoma. Recently, a SNP in the let-7 binding region of the KRAS 3' UTR was identified (termed LCS6). This functional polymorphism alters let-7 binding, resulting in both increased KRAS expression and decreased let-7 exposure. Further, this SNP has been reported as a risk trait for lung cancer among low-moderate smokers. Given the functionality of LCS6, we tested the hypothesis that this SNP is associated with the occurrence of KRAS mutation as well as patient survival. Here, we report there is no association between the LCS6 KRAS polymorphism and KRAS mutation. Further, we find no association between the LCS6 polymorphism and lung cancer survival. These unexpected findings imply that this newly reported KRAS-LCS6 polymorphism will have limited clinical utility for NSCLC.

Deafness on the island of Providencia - Colombia: different etiology, different genetic counseling.

Providencia is a small island located in the Caribbean Ocean, northwest of Colombia with an unusually high frequency of individuals with hearing loss (5 in 1,000) is present. The hearing loss in the island was characterized as non-syndromic autosomal recessive deafness accounting for 47% (8/17) of the deaf population, Waardenburg Syndrome (deafness associated with pigmentary anomalies) for 29% (5/17), and the remaining 24% (4/17) are cases of sporadic non-syndromic deafness. For appropriate genetic counseling a complete pedigree of families with deaf individuals was constructed. The 35delG mutation in GJB2 gene, which encodes connexin 26 (Cx26), is responsible for the deafness observed in the 8 individuals with autosomal recessive non-syndromic hearing loss. The deaf individuals with Waardenburg Syndrome and the sporadic cases did not have this mutation. Therefore, we present here an atypical case of an isolated community with at least two different genetic etiologies for deafness: non-syndromic genetic deafness caused by the 35delG mutation in the GJB2 gene and deafness associated with Waardenburg Syndrome not related to GJB2. In a small and isolated population, it is feasible to assume that the deafness is caused by the same factor; however, Providencia is an atypical case. Therefore, it is extremely important to define the exact etiology of deafness in each case, since different etiologies require different genetic counseling.

PBSC collection in extremely low weight infants: a single-center experience.

BACKGROUND: Peripheral blood progenitor cell (PBPC) collection has become the main source of hematopoietic cells for high-dose chemotherapy with stem cell rescue and, in some protocols, for allogeneic hematopoietic transplantation. This procedure is complicated in the smallest children because of difficulties related to their weight, and there is little published experience. We have conducted a prospective study to analyze the incidence of adverse events during PBPC collection in the smallest children (< or = 10 kg). METHODS: From January 2000 to November 2005, 257 leukapheresis were performed in our unit, and 13 of them (5%) in 12 children weighing up to 10 kg (median 9 kg, range 5.8-10.9 kg). RESULTS: Most cases had hypovolemic signs during the procedure (usually tachycardia); six cases had hypotension, five of them with pallor and diaphoresis, and, of those, two also had nausea. In all these cases infusion of saline or plasma volume expanders resolved the clinical findings. In two cases the nausea related to hypocalcemia was resolved after calcium gluconate infusion. Changes in platelet counts were also remarkable, with a median platelet loss of 52%. DISCUSSION: Leukapheresis with continuous-flow cell separators has frequent complications related to volume shift in the smallest children. These adverse events are mild and easily resolved with standard measures for hypovolemia, as plasma expander or normal saline infusions. However, we recommend that the procedure should only be performed by teams with extensive experience in the field.

Treatment of canine mast cell tumours with vinblastine, cyclophosphamide and prednisone: 35 cases (1997-2004).

The purpose of this retrospective study was to determine the efficacy and toxicity of a combined protocol of vinblastine, cyclophosphamide and prednisone (VCP) in 35 dogs with mast cell tumours (MCTs). Eleven dogs had measurable disease (group 1) and 24 dogs had incompletely excised MCT or were at high risk for metastasis (group 2). Five patients in group 1 achieved complete response, two partial responses, two stable diseases and two progressive diseases. The median progression-free survival time (PFST) for group 1 and 2 dogs was 74 and 865 days, respectively. The median overall survival time (OST) for group 1 and 2 dogs was 145 and >2092 days, respectively. Significant negative multivariate prognostic factors included macroscopic disease and reduced vinblastine (VBL) treatments for PFST, and presence of MCT in bone marrow analysis, Patnaik grade III MCT and reduced VBL treatments for OST. Toxicity was infrequent and self-limiting. This study suggests that the VCP protocol should be considered as an option in the treatment of MCT in dogs.

Comparison of CT during arterial portography and MR during arterial portography in the detection of liver metastases.

OBJECTIVE: This study compared MR during arterial portography (MRAP) with CT during arterial portography (CTAP) with regard to the detection and differentiation of liver metastases before surgery. MATERIALS AND METHODS: Fifteen patients with liver metastases were enrolled before surgery according to the guidelines of our institutional review board and good clinical practice. After mesentericography, unenhanced scans (Volume Zoom) were performed initially. For CTAP, the contrast medium was injected through the superior mesenteric artery. Images were acquired in portal and delayed enhancement. The MR protocol (1.5 T; Magnetom Symphony) started with T1-weighted fast low-angle shot (FLASH) T2-weighted turbo spin echo (TSE). MRAP followed with gadolinium-enhanced dynamic T1-weighted 3D FLASH. Delayed-phase T1-weighted 2D FLASH axial images were performed 2 min after IV injection of the contrast medium. Qualitative and quantitative evaluation of CTAP and MRAP was performed by three blinded radiologists regarding the number of lesions and their size, localization, and differential diagnosis. RESULTS: The overall sensitivity in detecting liver metastases was 97% with MRAP and 93% with CTAP (p > 0.05, not significant [n.s.]). The specificity was calculated to be 97% for MRAP and 82% for CTAP (p < 0.0001, statistically significant [s.s.]). The differences in sensitivity were more accentuated if only lesions 10 mm or smaller were considered (95% vs 88%, p > 0.05, n.s.), for which the respective specificities were 95% and 80% (p < 0.0014, s.s.). Improvements in sensitivity and specificity were associated with a higher lesion-to-liver contrast-to-noise ratio (59.4 +/- 51.0 for MRAP vs 10.4 +/- 7.3 for CTAP) and resulted in higher diagnostic confidence in the differential diagnosis of liver lesions (p < 0.001, s.s.) and better interobserver agreement (median kappa value, 0.88 vs 0.63). CONCLUSION: MRAP proved to be a reliable method in the preoperative detection of small liver metastases in particular, with a higher sensitivity and specificity than CTAP. If organizational difficulties of MRAP can be overcome, MRAP could be considered instead of CTAP in the preoperative invasive evaluation of metastatic liver disease.

Behçet's disease and hereditary periodic fever syndromes: casual association or causal relationship?

OBJECTIVE: Mutations in the MEFV and the type 1 TNF receptor (TNFRSF 1A) genes have recently been linked to familial Mediterranean fever (FMF) and TNF receptor-associated periodic syndrome (TRAPS), respectively. A higher prevalence of Behçet's disease (BD) among FMF patients has been described compared to the general population. The aim of this study was to evaluate whether FMF TRAPS and BD could be genetically related. METHODS: We screened a cohort of 50 BD patients and 100 healthy subjects for the common MEFV and TNFRSF 1A mutations. An initial screening of exons 10 and 2 of the MEFV gene and exon 4 of the TNFRSF 1A was performed in all chromosomes. RESULTS: The heterozygous MEFV mutation (K695R) was found in one (2%) BD patient. Analysis for FMF mutations in the control group revealed that 5 (5%) individuals bore MEFV gene mutations (3 were heterozygous for the E148Q and 2 were heterozygous for the A744S). At codon 202, there were no differences in allele frequencies between BD and control population: 73%R 27%Q in the BD patients vs 75%R 25%Q in controls. Concerning mutations in the TNFRSF 1A gene, the R92Q mutation was present in heterozygous state in one (2%) BD patient and in 4 (4%) controls without differences between allele frequencies: 99%R 1%Q in BD patients vs 98%R 2%Q in controls, respectively. There was no association between the clinical manifestations of BD patients and the presence of a particular polymorphism or a mutation. CONCLUSIONS: Neither FMF nor TRAPS are genetically associated with BD in our cohort of Spanish patients.

Hematopoietic transplantation for bone marrow failure syndromes and thalassemia.

Several genetic diseases, generally considered as congenital diseases, are characterized by bone marrow failure during early childhood. Hematopoietic stem cell transplantation is the only curative treatment for syndromes involving bone marrow failure and thalassemia. In this slate-of-the-art review, we wish to focus on the results of hematopoietic transplantation in treating some of these diseases, with a special emphasis on congenital bone marrow failure and thalassemia. The results of this procedure have improved over the previous years, mainly when performed by experienced teams. New conditioning regimes based on fludarabine and the use of HLA-identical donors have been related with better survivals. In the previous years, donors other than HLA-identical siblings have been increasingly used in patients not responding to conventional measures, but this approach needs to be evaluated in larger studies.

[Acute leukemia in patients with Down syndrome]. / Leucemia aguda en pacientes con síndrome de Down.

BACKGROUND: Children with Down syndrome (DS) have a higher risk of acute leukemia than the remaining pediatric population. A favorable outcome of acute myeloid leukemia (AML) has recently been described in these patients whereas the prognosis of acute lymphoblastic leukemias (ALL) is similar to that in other children. The main cause of morbidity and mortality in children with Down syndrome are complications related to chemotherapy, leading to numerous modifications in treatment protocols. OBJECTIVES: To characterize acute leukemias in children with Down syndrome in our center and determine their clinical outcome. METHODS AND RESULTS: Between 1990 and 2002, 214 children were diagnosed with acute leukemia at the Niño Jesus Hospital (40 with AML and 174 with ALL). Of these, eight children (3.8 %) had Down syndrome. AML (2/40) represented 5 % of myeloid leukemias and ALL (6/174) represented 3.4 % of lymphoblastic leukemias. The most frequent complication was hematologic toxicity due to chemotherapy, causing a high incidence of infections: pneumonia (5/8) and bacteriemia (5/8). In all patients, these complications led to treatment interruption or dose reduction. Two children died from treatment-related toxicity. Of these, one with AML developed fulminant sepsis due to Candida infection and the other, diagnosed with high risk ALL, died from multiorgan failure after high doses of methotrexate and ARA-C. CONCLUSIONS: Patients with Down syndrome diagnosed with acute leukemia show a higher incidence of treatment-related complications, which affects their prognosis. Consequently, individualized treatment of these children in qualified units is essential.