A common founder mutation in FANCA underlies the world's highest prevalence of Fanconi anemia in Gypsy families from Spain

Fanconi anemia (FA) is a genetic disease characterized by bone marrow failure and cancer predisposition. Here we have identified Spanish Gypsies as the ethnic group with the world's highest prevalence of FA (carrier frequency of 1/64-1/70). DNA sequencing of the FANCA gene in 8 unrelated Spanish Gypsy FA families after retroviral subtyping revealed a homozygous FANCA mutation (295C>T) leading to FANCA truncation and FA pathway disruption. This mutation appeared specific for Spanish Gypsies as it is not found in other Gypsy patients with FA from Hungary, Germany, Slovakia, and Ireland. Haplotype analysis showed that Spanish Gypsy patients all share the same haplotype. Our data thus suggest that the high incidence of FA among Spanish Gypsies is due to an ancestral founder mutation in FANCA that originated in Spain less than 600 years ago. The high carrier frequency makes the Spanish Gypsies a population model to study FA heterozygote mutations in cancer.     

Is pre-operative anaemia a risk marker for in-hospital mortality and morbidity after valve replacement?

AIMS: To assess the level of pre-operative haemoglobin (HB) as a risk marker for morbidity and mortality in the early post-operative period of patients who underwent elective valve replacement. METHODS AND RESULTS: Between January 1998 and March 2004, clinical and outcomes data were collected for the 201 patients who had elective valve replacement. For each gender, the criterion to choose the best cut-off point was that which achieved the maximum likelihood after several General Additive Model models performed in a Bootstrap procedure. The best cut-off point obtained for pre-operative HB was 12 g/dL. Overall peri-operative mortality (deaths occurring during hospital period or within 30 days) was 9.5%. After adjusting well-known independent pre-operative risk factors for operative mortality, pre-operative HB <12 g/dL was identified as an independent predictor for in-hospital mortality (OR, 3.23; 95% CI, 1.09-9.55; P = 0.03). Also adjusting for EuroScore, pre-operative HB remained significant (OR, 3.64; 95% CI, 1.32-10.06; P = 0.01). The same model was applied to post-operative morbidity, and pre-operative HB <12 g/dL was identified as an independent predictor with and without EuroScore (OR, 4.67; 95% CI, 2.03-10.71; P < 0.001), (OR, 5.18; 95% CI, 2.18-12.3; P < 0.001), respectively. CONCLUSION: In patients undergoing elective valve replacement pre-operative HB <12 g/dL is a risk marker of in-hospital mortality and serious adverse outcomes.     

Efficacy of atorvastatin and gemfibrozil,alone and in low dose combination,in the treatment of diabetic dyslipidemia

To compare the effects of atorvastatin, gemfibrozil, and their combination on the components of diabetic dyslipidemia, 44 type 2 diabetic patients with low density lipoprotein cholesterol (LDLc) levels greater than 100 mg/dl and triglyceride levels less than 400 mg/dl were included. Twelve-week treatments with atorvastatin (10-20 mg/d) and gemfibrozil (900-1200 mg/d) were given in random order in an open, cross-over study and then combined (10 mg atorvastatin and 900 mg gemfibrozil) for 12 additional wk. Triglyceride, LDLc, high density lipoprotein cholesterol (HDLc), non-HDLc, apolipoprotein B (apoB), and LDL size were measured at baseline and after each treatment. Atorvastatin was more effective (P < 0.001) in lowering LDLc, non-HDLc, and apoB and in achieving treatment goals, whereas gemfibrozil lowered triglyceride levels more effectively (P < 0.001) and increased LDL size (from 25.59 +/- 0.06 to 25.69 +/- 0.06 nm; P < 0.05). Combined treatment with both drugs reduced LDLc, triglyceride, non-HDLc, and apoB by 26.5%, 24.1%, 30.4%, and 21.8%, respectively; increased HDLc by 4.8% and LDL size by 0.1 nm; and was the most effective treatment in reaching the therapeutic targets, especially in patients with triglyceride levels higher than 150 mg/dl. In conclusion, statins are first choice drugs in diabetic patients with low to moderate risk LDLc, although their combination with fibrates might be the most appropriate treatment, especially when triglyceride levels are above the therapeutic goal.     

Seasonal Patterns of Buruli Ulcer Incidence,Central Africa, 2002–2012

To determine when risk for Buruli ulcer is highest, we examined seasonal patterns in a highly disease-endemic area of Cameroon during 2002–2012. Cases peaked in March, suggesting that risk is highest during the high rainy season. During and after this season, populations should increase protective behaviors, and case detection efforts should be intensified.     

Total fluid intake of children and adolescents: cross-sectional surveys in 13 countries worldwide

Purpose

To describe total fluid intake (TFI) according to socio-demographic characteristics in children and adolescents worldwide.

Methods

Data of 3611 children (4–9 years) and 8109 adolescents (10–18 years) were retrieved from 13 cross-sectional surveys (47 % males). In three countries, school classes were randomly recruited with stratified cluster sampling design. In the other countries, participants were randomly recruited based on a quota method. TFI (drinking water and beverages of all kinds) was obtained with a fluid-specific record over 7 consecutive days. Adequacy was assessed by comparing TFI to 80 % of adequate intake (AI) for total water intake set by European Food Safety Authority. Data on height, weight and socio-economic level were collected in most countries.

Results

The mean (SD) TFI ranged from [1.32 (0.68)] to [1.35 (0.71)] L/day. Non-adherence to AIs for fluids ranged from 10 % (Uruguay) to >90 % (Belgium). Females were more likely to meet the AIs for fluids than males (4–9 years: 28 %, OR 0.72, p = 0.002; 10–18 years: 20 %, OR 0.80, p = 0.001), while adolescents were less likely to meet the AI than children (OR 1.645, p < 0.001 in males and OR 1.625, p < 0.001 in females).

Conclusions

A high proportion of children and adolescents are at risk of an inadequate fluid intake. This risk is especially high in males and adolescents when compared with females or children categories. This highlights water intake among young populations as an issue of global concern.

     

Syncope in Patients With Severe Aortic Stenosis: More Than Just an Obstruction Issue

BackgroundSevere aortic stenosis (AoS) is considered a primary cause of syncope. However, other mechanisms may be present in these patients and accurate diagnosis can have important clinical implications. The aim of this study is to assess the different etiologies of syncope in patients with severe AoS and the impact on prognosis of attaining a certain or highly probable diagnosis for the syncope.MethodsOut of a cohort of 331 patients with AoS and syncope, 61 had severe AoS and were included in the study. Main cause of syncope and adverse cardiac events were assessed.ResultsIn 40 patients (65.6%), we reached a certain or highly probable diagnosis of the main cause of the syncope. AoS was considered the primary cause of the syncope in only 7 patients (17.5% of the patients with known etiology). Atrioventricular block (14 patients, 35.0%) and vasovagal syncope (6 patients, 15.0%) were the most frequently diagnosed causes. The presence of a known cause for syncope during the admission was not associated with a lower incidence of recurrence during follow-up (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.20-2.40). Syncope of unknown etiology was independently associated with greater mortality during 1-year follow-up (HR 5.4, 95% CI 1.3-21.6) and 3-year follow-up (HR 3.5, 95% CI 1.2-10.3).ConclusionsIn a high proportion of patients with severe AoS admitted for syncope, the valvulopathy was not the main cause of the syncope. Syncope in two-thirds of this population was caused by either bradyarrhythmia or reflex causes. Syncope of unknown cause was associated with increased short- and medium-term mortality, independently from treatment of the valve disease. An exhaustive work-up should be conducted to determine the main cause for syncope.     

Attenuated response to purified protein derivative in patients with rheumatoid arthritis: study in a population with a high prevalence of tuberculosis

BACKGROUND: The purified protein derivative (PPD) skin test is the only widely used method which detects latent tuberculosis infection (LTBI) and is dependent on a normal T cell function. In rheumatoid arthritis (RA) the T cell function is altered, which may result in an inability to develop an adequate PPD reaction. OBJECTIVES: To evaluate the response to PPD in patients with RA and to compare it with that of control subjects. METHODS: 112 patients with RA and 96 healthy controls were studied. PPD 5 U was applied using the Mantoux method, and skin reaction was measured at 72 hours. The reaction was considered negative for PPD <5 mm. RESULTS: There were no significant differences in age, sex, history of bacille Calmette-Guerin vaccination, or tuberculosis contact between the two groups. The median size of the PPD induration in the patients with RA was significantly less than that in the control group (4.5 v 11.5 mm, p<0.01). 79 (70.6%) patients with RA compared with 25 (26%) of the control group had a negative reaction to PPD (p<0.01), a response not influenced by disease activity or duration of disease in the patients with RA. CONCLUSION: A PPD skin test is not an appropriate test for recognising LTBI in patients with RA in our population.     

Practical recommendations for the use of ACE inhibitors, beta-blockers, aldosterone antagonists and angiotensin receptor blockers in heart failure: putting guidelines into practice

Surveys of prescribing patterns in both hospitals and primary care have usually shown delays in translating the evidence from clinical trials of pharmacological agents into clinical practice, thereby denying patients with heart failure (HF) the benefits of drug treatments proven to improve well-being and prolong life. This may be due to unfamiliarity with the evidence-base for these therapies, the clinical guidelines recommending the use of these treatments or both, as well as concerns regarding adverse events. ACE inhibitors have long been the cornerstone of therapy for systolic HF irrespective of aetiology. Recent trials have now shown that treatment with beta-blockers, aldosterone antagonists and angiotensin receptor blockers also leads to substantial improvements in outcome. In order to accelerate the safe uptake of these treatments and to ensure that all eligible patients receive the most appropriate medications, a clear and concise set of clinical recommendations has been prepared by a group of clinicians with practical expertise in the management of HF. The objective of these recommendations is to provide practical guidance for non-specialists, in order to increase the use of evidenced based therapy for HF. These practical recommendations are meant to serve as a supplement to, rather than replacement of, existing HF guidelines.