Relationship of lipid oxidation with subclinical atherosclerosis and 10-year coronary events in general population

Objectives

To assess 1) the association of lipid oxidation biomarkers with 10-year coronary artery disease (CAD) events and subclinical atherosclerosis, and 2) the reclassification capacity of these biomarkers over Framingham-derived CAD risk functions, in a general population.

Methods

Within the framework of the REGICOR study, 4782 individuals aged between 25 and 74 years were recruited in a population-based cohort study. Follow-up of the 4042 who met the eligibility criteria was carried out. Plasma, circulating oxidized low-density lipoprotein (oxLDL) and oxLDL antibodies (OLAB) were measured in a random sample of 2793 participants.End-points included fatal and non-fatal acute myocardial infarction (AMI) and angina. Carotid intima-media thickness (IMT) in the highest quintile and ankle-brachial index <0.9 were considered indicators of subclinical atherosclerosis.

Results

Mean age was 50.0 (13.4) years, and 52.4% were women. There were 103 CAD events (34 myocardial infarction, 43 angina, 26 coronary deaths), and 306 subclinical atherosclerosis cases. Oxidized LDL was independently associated with higher incidence of CAD events (HR = 1.70; 95% Confidence Interval: 1.02–2.84), but not with subclinical atherosclerosis. The net classification index of the Framingham-derived CAD risk function was significantly improved when ox-LDL was included (NRI = 14.67% [4.90; 24.45], P = 0.003). No associations were found between OLAB and clinical or subclinical events. The reference values for oxLDL and OLAB are also provided (percentiles).

Conclusions

OxLDL was independently associated with 10-year CAD events but not subclinical atherosclerosis in a general population, and improved the reclassification capacity of Framingham-derived CAD risk functions.     

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m²), mitoxantrone (MXR, 12 mg/m²), or idarubicin (IDA, 10 mg/m²) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.     

pFDR and pFNR estimation for brain networks construction

Recent developments in the study of brain functional connectivity are widely based on graph theory. In the current analysis of brain networks, there is no unique way to derive the adjacency matrix, which is a useful representation for a graph. Its entries, containing information about the existence of links, are identified by thresholding the correlation between the time series that characterized the dynamic behavior of the nodes. In this work, we put forward a strategy to choose a suitable threshold on the correlation matrix considering the problem of multiple comparisons in order to control the error rates. In this context we propose to control the positive false discovery rate (pFDR) and a similar measure involving false negatives, called the positive false nondiscovery rate (pFNR). In particular, we provide point and interval estimators for pFNR and a method for balancing the two types of error, demonstrating it by using functional magnetic resonance imaging data and Monte Carlo simulations. Copyright © 2013 John Wiley & Sons, Ltd.     

Occupational laryngitis caused by formaldehyde: A case report

Formaldehyde is commonly accepted to be an allergen and irritant. However, specifically diagnosed occupational respiratory diseases caused by formaldehyde are relatively rare. Occupational laryngitis was diagnosed in a 47-year-old dairy foreman. He had been exposed for 9 years to formaldehyde emitted from a milk-packing machine situated underneath his office. His exposure level varied considerably. Under normal process conditions, the measured formaldehyde level was 0.03 mg/m³. The patient was examined by different specialists over 1½ years. It was concluded that that he had psychogenic dysphonia. However, a specific laryngeal provocation test with formaldehyde carried out at the Finnish Institute of Occupational Health was positive. His laryngitis was so serious that he was pensioned. During the 3 years of follow-up his condition gradually worsened. He now reacts especially to tobacco smoke and other air impurities known to contain formaldehyde. © 1996 Wiley-Liss, Inc.     

Development and psychometric properties of the “Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales” in adolescents

European Child & Adolescent Psychiatry - Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and...     

Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adenomatous polyposis. Hereditary Colorectal Tumors Registry

OBJECTIVE: To identify factors influencing the occurrence of cancer in the rectal remnant in patients with familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). SUMMARY BACKGROUND DATA: The risk for rectal cancer in patients with FAP after colectomy and IRA remains a major concern. METHODS: Between 1955 and 1997, 371 patients (206 men, 165 women) from the Registry of Hereditary Colorectal Tumors underwent colectomy and IRA as a primary surgical procedure. Survival was estimated using the Kaplan-Meier method. Cox proportional hazard models were fitted to assess the relative excess risk of rectal cancer and to control for confounding factors. A multivariate analysis was performed to assess the relation between cancer risk in the rectum and sex, age, number of rectal polyps, colon cancer, and APC germline mutation. RESULTS: Median follow-up was 81 months. Eighty-nine patients (24%) had colon cancer at the time of surgery. The APC mutation was found in 200 patients. In 27 patients, cancer developed in the retained rectum 1 to 26 years after surgery. The incidence of rectal carcinoma appears to increase with time: at 10, 15, and 20 years after surgery, the cumulative risk was 7.7%, 13.1%, and 23.0%, respectively. Multivariate analysis identified as independent predictors the presence of colon cancer at IRA and a mutation occurring between codons 1250 and 1464; both factors increased the risk nine times. CONCLUSIONS: The presence of cancer at IRA and APC mutation type are the most important risk factors for the future development of cancer in the rectal remnant in patients with FAP.     

Follow-up study of thyroid function in polytransfused thalassemic patients

The aim of our investigation was to evaluate thyroid function by a follow-up study in 45 polytransfused thalassemic patients, since endocrine abnormalities are frequent consequences of iron overload in thalassemia major. Significant changes of thyroid function have been revealed in the time elapsing the observation, despite unchanged haematological parameters; at the end of the present study five patients were affected by overt hypothyroidism and 15 patients by subclinical hypothyroidism. Ultrasound thyroid volume in 13 randomly selected patients was greatly reduced, while thyroid Magnetic Resonance Imaging (MRI) was not able to detect tissue alterations. Inversely, liver MRI was markedly reduced in 14 patients and negatively related to ferritine levels (P< 0.01). We conclude that polytransfused thalassemics are frequently affected by thyroid disfunction; haepatic haemosiderosis due to iron overload seems influence hormonal peripheral metabolism, although the patients display a moderate compliance with iron chelation therapy. Therefore, periodic thyroid investigation should be carried out in thalassemic subjects in order to detect patients who need hormone replacement therapy.     

MRI angiography is superior to helical CT for detection of HCC prior to liver transplantation: an explant correlation

Helical computerized tomography (CT) and magnetic resonance imaging (MRI) are used for staging of hepatocellular carcinoma (HCC) prior to curative treatments but underestimate tumor extension in 30% to 50% of cases when compared with pathologic explants. This study compares a new technology, MRI angiography (MRA), with triphasic helical CT in detection of HCC. Fifty cirrhotic patients, 29 with HCC, undergoing liver transplantation were analyzed. MRA was performed with a 3-D breath-hold fast spoiled gradient-echo sequence by using an effective section thickness of 2 to 2.5 mm. The gold standard was the pathologic examination (liver cut into 5-mm slices). One hundred twenty-seven lesions were identified at the explant: 76 HCC, 13 high-grade dysplastic nodules, 31 macroregenerative nodules, 7 hemangiomas. Diameter of the main HCC nodules was 29 +/- 14 mm and 11 +/- 7 mm for the 47 additional nodules. On a per nodule basis, sensitivity of MRA was superior to CT (58/76 [76%] vs. 43/70 [61%], respectively, P =.001). Sensitivity of MRA for detection of additional nodules decreased with size (>20 mm: 6/6 [100%]; 10-20 mm: 16/19 [84%]; <10 mm: 7/22 [32%]) and was superior to CT for nodules 10 to 20 mm (84% vs. 47%, P =.016). Nonspecific hypervascular nodules >5 mm at MRA were HCC in two thirds of the cases. In conclusion, MRA has a high diagnostic accuracy for HCC > or =10 mm and is more sensitive than triphasic helical CT in nodules sized 10 to 20 mm. MRA is the optimal technique for HCC staging prior to curative therapies.     

A unique MSH2 exon 8 deletion accounts for a major portion of all mismatch repair gene mutations in Lynch syndrome families of Sardinian origin

Lynch syndrome is an autosomal-dominant hereditary condition predisposing to the development of specific cancers, because of germline mutations in the DNA-mismatch repair (MMR) genes. Large genomic deletions represent a significant fraction of germline mutations, particularly among the MSH2 gene, in which they account for 20% of the mutational spectrum. In this study we analyzed 13 Italian families carrying MSH2 exon 8 deletions, 10 of which of ascertained Sardinian origin. The overrepresentation of Sardinians was unexpected, as families from Sardinia account for a small quota of MMR genes mutation tests performed in our laboratory. The hypothesis that such a result is owing to founder effects in Sardinia was tested by breakpoint junctions sequencing and haplotype analyses. Overall, five different exon eight deletions were identified, two of which recurrent in families, all apparently unrelated, of Sardinian origin (one in eight families, one in two families). The c.1277–1180_1386+2226del3516insCATTCTCTTTGAAAA deletion shares the same haplotype between all families and appears so far restricted to the population of South-West Sardinia, showing the typical features of a founder effect. The three non-Sardinian families showed three different breakpoint junctions and haplotypes, suggesting independent mutational events. This work has useful implications in genetic testing for Lynch syndrome. We developed a quick test for each of the identified deletions: this can be particularly useful in families of Sardinian origin, in which MSH2 exon 8 deletions may represent 50% of the overall mutational spectrum of the four MMR genes causing Lynch syndrome.