Usefulness of circulating biomarkers for the prediction of left ventricular remodeling after myocardial infarction

Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a high risk of heart failure and death, but LV remodeling remains difficult to predict. Biomarkers may help to refine risk stratification for a more personalized medical approach. They may also shed light on the pathophysiologic processes involved. We performed a systematic review of the published evidence about the association of circulating biomarkers with LV remodeling after MI. We selected 59 publications. Overall, these studies examined 112 relations between 52 different biomarkers and LV remodeling. The biomarkers most consistently associated with LV remodeling were involved in extracellular matrix turnover or neurohormonal activation: matrix metalloproteinase-9, collagen peptides, and B-type natriuretic peptide. This review underscores the vitality of the research on LV remodeling but concludes that the ideal biomarker has not yet been identified. To reach this goal, future studies will have to be larger, have standardized imaging end points, and include replication populations to define optimal cutoffs for LV remodeling prediction. Cardiovascular magnetic resonance appears to be the best technique for LV remodeling assessment but its current availability may be a concern for recruitment for multicenter studies. Recent technologic advances will probably yield new candidate biomarkers of LV remodeling. Tests are necessary to determine whether a multimarker approach would significantly improve risk prediction.     

Validation of a short food frequency questionnaire to evaluate nutritional lifestyles in hypercholesterolemic patients

ObjectivesThe purpose of our study was to develop and validate a short food frequency questionnaire which could assess the nutritional lifestyles of hypercholesterolemic patients consulting in daily practice.Material and methodsThe questionnaire explores 11 nutrient categories. Hundred and thirty-one patients were recruited for the construct validity and 58 patients for the external validity in La Pitié Hospital, Paris. The reference method used was the diet history. To measure the internal consistency and to test the sensibility to change on a large scale, the questionnaire was used in an observational study conducted in Spain in 1048 moderate hypercholesterolemic patients. Psychometric analyses included construct validity, internal consistency, test-retest reliability, external validity and sensibility to change.ResultsValidation of the questionnaire indicated a good internal consistency (Cronbach Coefficient Alpha at 0.69) and test-retest reliability (intraclass correlation coefficient = 0.89). The correlation between the scores of the FFQ and those of the diet history was significant with a Pearson correlation coefficient at 0.3 (P = 0.029). The comparison between the ranking of the patients showed an agreement of 72% with a kappa of 0.48 [0.10; 0.69]. The sensibility to change was good with a score evolution improving one and four months after nutrition advices: 28.2% of patients ranked in group 1 at inclusion versus 61.3% (P < 0.0001) at one month and 75.2% (P < 0.0001) at four months.ConclusionIn conclusion, we developed and validated a food questionnaire for hypercholesterolemic patients, which can be used as a therapeutic education tool in daily practice or in clinical research.     

Proximity to HIV is associated with a high rate of HIV testing among men who have sex with men living in Douala, Cameroon

In low- and middle-income countries, men who have sex with men (MSM) are 19 times more likely to be HIV positive compared with background populations. Criminalisation and social rejection of homosexuality in most sub-Saharan African countries reinforce stigma and exclude MSM from prevention activities, including HIV testing. This paper's purpose is to identify factors associated with never having been HIV tested (NHT), among a sample of Cameroonian MSM. In 2008, a community-based study was conducted in Douala, the economic capital city of Cameroon, by a local NGO Alternatives-Cameroun, recruiting participants through the snowball technique and administering a questionnaire during face-to-face interviews. Proximity to HIV was investigated according to the following criteria: knowing at least one person living with HIV and having been exposed to HIV prevention interventions. NHT was defined as reporting to have never been HIV tested. A logistic regression was used to identify factors associated with NHT. Among the 165 MSM of our study group who reported that they were not HIV positive, 19% reported NHT. Factors independently associated with NHT were as follows: being younger, being Muslim, not having a steady male partner, not knowing any person living with HIV and never having been exposed to HIV prevention interventions. In this MSM population, a small proportion reported that they had never been HIV tested and among these, the percentage was higher among individuals not in proximity to HIV. Despite the hostile context of sub-Saharan African countries towards MSM, local and national HIV testing campaigns to date may have played a substantial role in raising HIV awareness in the MSM population living in Douala, and peer-based counselling may have educated those in contact with Alternatives-Cameroun regarding the positive value of HIV testing. This result is a further argument for continuing community-based prevention and extending it to difficult-to-reach MSM.     

Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 μg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 μg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.     

The impact of lymph node status and features on oncological outcomes in urothelial carcinoma of the upper urinary tract (UTUC) treated by nephroureterectomy

Purpose

Prognostic impact of lymphadenectomy during radical nephroureterectomy (RNU) for urothelial carcinoma of the upper urinary tract (UTUC) is controversial. Our aim was to assess the impact of lymph node status (LNS) on survival in patients treated by RNU.

Methods

In our multi-institutional, retrospective database, 714 patients with non-metastatic UTUC had undergone RNU between 1995 and 2010. LNS was tested as prognostic factor for survivals through univariate and multivariable Cox regression analysis.

Results

Median age was 70 years [interquartile range (IQR), 60–75] with median follow-up of 27 months (IQR, 10–50). Overall, lymphadenectomy was performed in 254 patients (35.5 %). Among these patients, 204 (80 %) had negative lymph nodes (pN0) and 50 (20 %) had positive lymph nodes (pN1/2). The 5-year cancer-specific survival (CSS) was 81 % [95 % confidence interval (CI), 73–88 %] for pN0 patients, 85 % (95 % CI, 80–90 %) for pNx patients and 47 % (95 % CI, 24–69 %) for pN1/2 patients (p < 0.001). Metastasis-free survival (MFS) and overall survival (OS) rates were significantly lower in pN1/2 patients than in pN0 and pNx patients (p < 0.05). On multivariable analysis, LNS did not appear as an independent prognostic factor for CSS, OS or MFS (p > 0.05). In case of lymph node involvement, extra-nodal extension was marginally associated with worse CSS (log rank p = 0.07). The retrospective design was the main limitation.

Conclusion

LNS is helpful for survival stratification in patients treated with RNU for UTUC. However, LNS did not appear as an independent predictor of survival in this retrospective series and needs to be investigated in a large multicentre, prospective evaluation.