Characteristics, management, and outcomes of active cancer patients with cardiogenic shock.

AIMS: Characteristics, management, and outcomes of patients with active cancer admitted for cardiogenic shock remain largely unknown. This study aimed to address this issue and identify the determinants of 30-day and 1-year mortality in a large cardiogenic shock cohort of all aetiologies. METHODS AND RESULTS: FRENSHOCK is a prospective multicenter observational registry conducted in French critical care units between April and October 2016. 'Active cancer' was defined as a malignancy diagnosed within the previous weeks with planned or ongoing anticancer therapy. Among the 772 enrolled patients (mean age 65.7 ± 14.9 years; 71.5% male), 51 (6.6%) had active cancer. Among them, the main cancer types were solid cancers (60.8%), and hematological malignancies (27.5%). Solid cancers were mainly urogenital (21.6%), gastrointestinal (15.7%), and lung cancer (9.8%). Medical history, clinical presentation, and baseline echocardiography were almost the same between groups. In-hospital management significantly differed: patients with cancers received more catecholamines or inotropes (norepinephrine 72% vs. 52%, P = 0.005 and norepinephrine-dobutamine combination 64.7% vs. 44.5%, P = 0.005), but had less mechanical circulatory support (5.9% vs. 19.5%, P = 0.016). They presented a similar 30-day mortality rate (29% vs. 26%) but a significantly higher mortality at 1-year (70.6% vs. 45.2%, P < 0.001). In multivariable analysis, active cancer was not associated with 30-day mortality but was significantly associated with 1-year mortality in 30-day survivors [HR 3.61 (1.29-10.11), P = 0.015]. CONCLUSION: Active cancer patients accounted for almost 7% of all cases of cardiogenic shock. Early mortality was the same regardless of active cancer or not, whereas long-term mortality was significantly increased in patients with active cancer.

Effect of Sex on Outcomes of Coronary Rotational Atherectomy Percutaneous Coronary Intervention (From the European Multicenter Euro4C Registry).

Data regarding the potential influence of gender on outcomes of rotational atherectomy (RA) percutaneous coronary intervention (PCI) are scarce and conflicting. Using the Euro4C registry, an international prospective multicentric registry of RA PCI, we evaluated the influence of gender on clinical outcomes of RA PCI. Between October 2016 and July 2018, 966 patients were included. In them, 267 (27.6%) were females. Female patients were older than males (77.7 years old ± 9.8 vs 73.3 ± 9.5 years old respectively, p < 0.001) had a poorer renal function (43,1% of females had a GFR < 60 ml/min:1.73m² vs 30.4% of males, p < 0.001) and were more frequently admitted for an acute coronary syndrome (32.2% vs 22.3% p = 0.002). During RA procedure, women were less likely to be treated by radial approach (65.0% vs 74.4%, p = 0.004). In-hospital major adverse cardiac event rate-defined as cardiovascular death, myocardial infarction, stroke/transient ischemic attack, target lesion revascularization, and coronary artery bypass grafting surgery-was higher in the female group (7.1% vs 3.7%, p = 0.043). However, coronary perforation, dissection, slow/low flow and tamponade did not significantly differ in gender, neither did cardiovascular medications at discharge. At 1 year follow-up, rate of major adverse cardiac event was 18.4% in the female group vs 11.2% in the male group (adjusted Hazard Ratio 1.82 [1.24 to 2.67], p = 0.002). No significant bleeding differences were observed in gender, neither in hospital, nor during follow-up. In conclusion women had worse clinical outcomes following RA PCI during hospitalization and at 1 year follow-up than did men.

Impact of aortic valve calcification severity on device success after transcatheter aortic valve replacement.

Aortic valvular calcium score (AVCS) can identify severe aortic stenosis (AS) and provide powerful prognostic information. In severe and symptomatic AS, patients can be referred for a transcatheter aortic valve replacement (TAVR). The aim of this study was to determine whether AVCS, measured on the preoperative contrast enhanced multislice computed tomography (MSCT), is associated with device success (DS), major adverse cardiac events (MACEs) and paravalvular leak (PVL) after TAVR. Three hundred and fifty-two consecutive patients who underwent TAVR with a preoperative standardised contrast enhanced MSCT were included in the study. Valvular calcification detection was defined by adding + 100 Hounsfield Unit (HU) to mean HU determined by a region of interest placed in the contrast enhanced ascending aorta. AVCS was then indexed to the aortic annulus surface (AVCSi). Endpoints were DS and 30-day MACE according to Valve Academic Research Consortium-2 consensus document, and moderate to severe PVL. DS was obtained for 305 patients. In multivariate analysis, AVCSi was negatively and independently associated with DS: OR = 0.99, 95% CI 0.99-0.99, p = 0.03. In the subgroup analysis, this association was particularly relevant with self-expanding prostheses [n = 151 (43%), p = 0.018] and in the cases of asymmetric calcium valvular distribution [n = 283 (80%), p 0.002]. There was no association between MACE and AVCS (p = 0.953) and AVCSi (p = 0.757). PVL was positively associated with AVCS (p < 0.001) and AVCSi (p < 0.001). In conclusion, in TAVR, AVCS, measured on preoperative contrast enhanced MSCT, is significantly associated with DS and PVL, but not with 30-day MACE. Its routine use could be relevant to appreciate success chances of TAVR.

Management of patients with acute ST-elevation myocardial infarction: Results of the FAST-MI Tunisia Registry.

BACKGROUND: The FAST-MI Tunisia registry was set up by the Tunisian Society of Cardiology and Cardiovascular Surgery to assess the demographic and clinical characteristics, management and hospital outcome of patients with ST-elevation myocardial infarction (STEMI). METHODS: Data for 459 consecutive patients (mean age 60.8 years; 88.5% male) with STEMI, treated in 16 public hospitals (representing 72.2% of public hospitals in Tunisia treating STEMI patients), were collected prospectively.The most common risk factors were smoking (63.6%), hypertension (39.7%), diabetes (32%) and dyslipidaemia (18.2%). RESULTS: Among the 459 patients, 61.8% received reperfusion therapy: 30% with primary percutaneous coronary intervention (PPCI) and 31.8% with intravenous fibrinolysis (IF) (28.6% with pre-hospital thrombolysis). The median time from symptom onset to thrombolysis was 185 min and to PPCI was 358 min. In-hospital mortality was 5.3%. Compared with those managed at regional hospitals, patients managed at interventional university hospitals (n = 357) were more likely to receive reperfusion therapy (52.9% vs. 34.1%; p<0.001), with less IF (28.6% vs. 43.1%; p = 0.002) but more PPCI (37.8% vs. 3.9%; p<0.0001). However, in-hospital mortality in the two types of hospitals was similar (5.3% vs. 5.1%; p = 0.866). CONCLUSIONS: Data from the FAST-MI Tunisia registry show that a pharmaco-invasive strategy of management for STEMI should be promoted in non-interventional regional hospitals.

Increased mortality risk in diabetic patients discharged from hospital with insulin therapy after an acute myocardial infarction: Data from the FAST-MI 2005 registry.

BACKGROUND: Merits of insulin use for diabetes treatment in patients with advanced atherosclerosis are debated. This observational study conducted in diabetic patients after an acute myocardial infarction aimed to assess whether insulin prescription at discharge (IPD) was related to all-cause mortality during follow-up. METHODS: Subjects were diabetic patients admitted in intensive- or coronary-care units for acute myocardial infarction (consecutively recruited in 223 centres in France) and discharged alive from the hospital, with or without an IPD. Vital status after five years was obtained and the relationship between insulin prescription at discharge and survival was studied. RESULTS: Overall, 1221 diabetic patients were discharged alive and 38% had an IPD. Factors independently related to IPD were female gender, hospitalization in a public hospital, duration of diabetes, HbA1c level, smoking, peripheral artery disease, history of coronary heart disease and Killip class. After adjustment, IPD was independently related to all-cause mortality after five years of follow-up (adjusted hazard ratio = 1.72 (1.42-2.09), p<0.001). This increased mortality in subjects with IPD was also observed in propensity matched analyses, when subjects actually treated or actually not treated with insulin at discharge were compared in two groups matched on their computed probability of having had insulin prescribed. CONCLUSIONS: Insulin was preferably prescribed in seriously affected patients, regarding diabetes and cardiovascular risk. However, insulin prescription at discharge was associated with increased all-cause mortality after extensive adjustments for confounders. These results suggest possible intrinsic harmful effects of insulin in high-risk diabetic patients after myocardial infarction.

Comparison of Ankle Pressure, Systolic Toe Pressure, and Transcutaneous Oxygen Pressure to Predict Major Amputation After 1 Year in the COPART Cohort.

The hemodynamic definition of critical limb ischemia (CLI) has evolved over time but remains controversial. We compared the prediction of major amputation by 3 hemodynamic methods. Patients were selected from the Cohorte des Patients ARTériopathes cohort of patients hospitalized for peripheral arterial disease. Patients with CLI were enrolled according to the Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease II definition and followed up for at least 1 year. We compared the major amputation rate according to initial ankle pressure (AP), systolic toe pressure (STP), and forefoot transcutaneous oxygen pressure (TcPO2); 556 patients were included and divided into surgical (264) and medical (292) groups. The AP failed to identify 42% of patients with CLI. After 1 year, 27% of medical and 17% of surgical patients had undergone major amputation. The TP <30 mm Hg predicted major amputation in the whole sample and in the medical group (odds ratio [OR] 3.5 [1.7-7.1] and OR 5 [2-12.4], respectively), but AP did not. The TcPO2 <10 mm Hg also predicted major amputation (OR 2.3 [1.5-3.5] and OR 3.8 [2.1-6.8]). The best predictive thresholds to predict major amputation were STP <30 mm Hg and TcPO2 <10 mm Hg. None of these methods performed before surgery was able to predict outcome in the revascularized patients.

Peripheral Atheromatous Arterial Disease in the Young: Risk Factors, Clinical Features, and Prognosis From the COPART Cohort.

We describe the cardiovascular risk factors, clinical presentation, and prognosis in a comparative study of patients with peripheral artery disease (PAD) from the Cohorte des Patients ARTériopathes (COPART) cohort, which includes patients hospitalized for PAD in France. Among the 2514 patients included in the cohort, 189 had PAD before or at the age of 50 years and 2325 had it after. Young patients with PAD had diabetes less frequently (34% vs 46%, P < .001), were more frequent active smokers (58% vs 23%, P < 0.001), had lower high-density lipoprotein cholesterol (HDL-C; 41 ± 14 vs 44 ± 15 mg/dL, P = .026), and had a less frequent family and personal history of coronary heart disease. In a subset of 59 patients whose lipoprotein (a) (Lp(a)) was measured, the Lp(a) levels were higher in the young patients than in the older ones (89.7 mg/dL [9.7-151.3] vs 19.9 mg/dL [3.0-207.9], P = .004). Survival and amputation-free survival was 2.2 times higher (1.5-3.2, P < .001) in the young after 1 year. The onset of PAD before 50 years was associated with active smoking, low HDL-C, high Lp(a), and lower mortality.

Mitral Annular Calcium and Mitral Stenosis Determined by Multidetector Computed Tomography in Patients Referred for Aortic Stenosis.

Mitral annular calcium (MAC) is a common finding in older patients referred for transcatheter aortic valve implantation (TAVI). Multidetector computed tomography (MDCT) allows fine quantification of the calcific deposits. Our objective was to estimate the prevalence of MAC and associated mitral stenosis (MS) in patients referred for TAVI using MDCT. A cohort of 346 consecutive patients referred for TAVI evaluation was screened by MDCT for MAC: 174 had MAC (50%). Of these patients, 165 patients (95%) had mitral valve area (MVA) assessable by MDCT planimetry (age 83.8 ± 5.9 years). Median mitral calcium volume and MVA were 545 mm3 (193 to 1,253 mm3) and 234 mm2 (187 to 297 mm2), respectively. The MS was very severe, severe, and moderate in 2%, 22%, and 10% patients, respectively. By multivariate analysis, MVA was independently correlated to mitral calcium volume, aortic annular area, and some specific patterns of mitral leaflet calcium. Based on these findings, a formula was elaborated to predict the presence of a significant MS. In conclusion, MDCT allows detailed assessment of MAC in TAVI populations, demonstrating a high prevalence. Mitral analysis should become routine during MDCT screening before TAVI as it may alter therapeutic strategy.

Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients.

Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5% had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46%. The clinical response of the 37 targeted lesions led to an OOR of 51% and a DCR of 75%. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3-/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed.

Effectiveness of screening for abdominal aortic aneurysm during echocardiography.

Screening patients with abdominal aortic aneurysm (AAA) is associated with reduced AAA-related mortality, but population screening is poorly implemented. Opportunistic screening during imaging for other indications might be efficient. Single-center series reported AAA rates of 0.8% to 6.5% in patients undergoing transthoracic echocardiography (TTE), with disparities due to selection bias. In this first multicenter study, we aimed to assess the feasibility and criteria for screening AAA during TTE in real-life practice. During a week of May 2011, 79 centers participated in a nationwide survey. All patients aged ≥65 years requiring TTE for any indication were eligible, except for those with operated abdominal aorta. We defined AAA by an anteroposterior diameter of the infrarenal aorta≥30 mm. Of 1,382 consecutive patients, abdominal aorta imaging was feasible in 96.7%, with a median delay of 1.7 minutes (>3 minutes in 3.6% of cases). We found AAA in 50 patients (3.7%). Unknown AAA (2.7%) was more frequent in men than women (3.7% vs 1.3%, respectively, p=0.007) and increased by age at 2.2%, 2.5%, and 5.8% in age bands of 65 to 74, 75 to 84, and 85+ years, respectively. None of the female participants aged <75 years had AAA. Smoking status and family history of AAA were significantly more frequent among patients with AAA. The ascending aorta was larger in those with AAA (36.2±4.7 vs 34.0±5.2 mm, p=0.006), and bicuspid aortic valve and/or major aortic regurgitation were also more frequent (8% vs 2.6%, p=0.017). In conclusion, rapid AAA screening during TTE is feasible and should be limited to men ≥65 years and women≥75 years.

TG1042 (Adenovirus-interferon-γ) in primary cutaneous B-cell lymphomas: a phase II clinical trial.

RATIONAL: While a variety of registered therapies exist for Cutaneous T Cell Lymphoma, no such therapy is available for Cutaneous B Cell Therapy. In this context we performed a phase II, open label, multicenter, non-comparative study to evaluate the efficacy and safety of repeated intra-lesional administrations of TG1042 (adenovirus-interferon-γ) in patients with relapsing primary cutaneous B-cell lymphomas (CBCL). METHOD: Thirteen patients have been enrolled and received intralesional injections of TG1042 containing 5×10(10) viral particles into up to six lesions simultaneously. Injections were performed on days 1, 8 and 15 of each of four consecutive 28 day cycles. RESULTS: Eleven (85%) out of 13 enrolled patients showed an objective response after injections of TG1042. Seven patients (54%) exhibited complete and four (31%) displayed partial response. The median time to disease progression in the study population was 23.5 months (range 6.25 to 26+). Most commonly observed adverse events were minor to moderate flu-like symptoms, fatigue and injection site reactions. CONCLUSIONS: Our study showed that treatment with TG1042 was associated with a clinical benefit in the majority of the patients with relapsing CBCL, including tumor regression, a clinically meaningful duration of response and a good treatment tolerance. TRIAL REGISTRATION: www.clinicaltrials.govNCT00394693.

Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042.

BACKGROUND: Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL). METHODS: For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient's objective response at the end of the study. RESULTS: Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit. CONCLUSIONS: These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response. TRIAL REGISTRATION: The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693.

Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry.

BACKGROUND: Clopidogrel requires metabolic activation by cytochrome P450 2C19 (CYP2C19). Proton pump inhibitors (PPIs) that inhibit CYP2C19 are commonly coadministered with clopidogrel to reduce the risk of gastrointestinal bleeding. This analysis compares treatment outcomes for patients in the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) who did or did not receive clopidogrel and/or PPIs. METHODS AND RESULTS: The FAST-MI registry included 3670 patients (2744 clopidogrel- and PPI-naïve patients) presenting with definite MI. Patients were categorized according to use of clopidogrel and/or PPI within 48 hours after hospital admission. PPI use was not associated with an increased risk for any of the main in-hospital events (in-hospital survival, reinfarction, stroke, bleeding, and transfusion). Likewise, PPI treatment was not an independent predictor of 1-year survival (hazard ratio, 0.97; 95% confidence interval [CI], 0.87 to 1.08; P=0.57) or 1-year MI, stroke, or death (hazard ratio, 0.98; 95% CI, 0.90 to 1.08; P=0.72). No differences were seen when the type of PPI or CYP2C19 genotype was taken into account. In the propensity-matched cohorts, the odds ratios for major in-hospital events in PPI versus no PPI were 0.29 (95% CI, 0.06 to 1.44) and 1.70 (95% CI, 0.10 to 30.3) for patients with 1 and 2 variant alleles, respectively. Similarly, the hazard ratio for 1-year events in hospital survivors was 0.68 (95% CI, 0.26 to 1.79) and 0.55 (95% CI, 0.06 to 5.30), respectively. CONCLUSION: PPI use was not associated with an increased risk of cardiovascular events or mortality in patients administered clopidogrel for recent MI, whatever the CYP2C19 genotype, although harm could not be formally excluded in patients with 2 loss-of-function alleles.

Impact of polyvascular disease on baseline characteristics, management and mortality in acute myocardial infarction. The Alliance project.

BACKGROUND: A substantial number of patients with acute myocardial infarction (AMI) have polyvascular disease (PolyVD), defined as cerebrovascular disease (CVD), peripheral arterial disease (PAD) or both. AIM: To investigate the impact of PolyVD on baseline characteristics, management and outcomes. METHODS: The Alliance project is a multicentre, cross-sectional database of patients with myocardial infarction throughout France from 2000 to 2005. A pooled analysis of individual patient data was performed by aggregating data from five registries, representing 9783 patients hospitalized for acute coronary syndromes. Data were collected on history of PAD and CVD and correlated to baseline characteristics, management and hospital outcomes. RESULTS: Eight thousand nine hundred and four patients had full datasets for this analysis (13% with a history of CVD or PAD, 87% without). Patients with PolyVD were older (72 vs 65 years, p<0.0001), had a more frequent history of AMI (26% vs 15%, p<0.0001), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), renal insufficiency (12% vs 3%, p<0.0001) and consistently more risk factors for atherosclerosis (hypertension, dyslipidaemia, smoking, diabetes), but less frequently a body mass index>30 kg/m(2) (14.0% vs 20.1%, p<0.0001) compared to patients with coronary artery disease (CAD) alone. Killip class, left-ventricular ejection fraction and GUSTO risk score were all worse among patients with PolyVD. Management of patients with PolyVD was less aggressive (with later admission and less frequent use of in-hospital angiography or evidence-based therapies at discharge). Mortality of patients with PolyVD was consistently higher than in those with CAD alone, regardless of age. Multivariable analysis, adjusting for age, showed that both PAD (odds ratio 1.36 95% confidence interval 1.03-1.79) and history of CVD (odds ratio 1.74, 95% confidence interval 1.27-2.40) were independent predictors of hospital mortality relative to patients with CAD only. CONCLUSION: Patients with PolyVD represented a substantial group among AMI patients, at particularly high risk of death, yet were managed less aggressively than patients with CAD alone. This was associated with markedly higher in-hospital mortality. Further research is warranted to design and test strategies to decrease mortality in this high-risk subset.

Phase II clinical trial of intratumoral application of TG1042 (adenovirus-interferon-gamma) in patients with advanced cutaneous T-cell lymphomas and multilesional cutaneous B-cell lymphomas.

Cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative disorders that are manageable by immunotherapy. Twenty-one patients were enrolled in a prospective open-label, dose-escalation multicenter study evaluating the effects of repeated TG1042 [adenovirus-interferon (IFN)-gamma] intralesional injections in patients with primary CLs, of which 18 were of T-cell and 3 of B-cell type. Repeated intralesional therapy using TG1042 consistently results in local tumor regressions in about half of treated patients and one-third of patients also in regressions in noninjected distant lesions, likely reflecting the systemic immune activation after intralesional therapy. Treatment was well tolerated with few adverse events including injection site reactions, chills, lymphopenia, and fever. Immune monitoring in the peripheral blood demonstrated systemic immune activation and the induction of antibodies against tumor antigens in some patients without clear association with clinical responses. CLs, in particular B-cell lymphomas with high objective response rates, seem to be excellent targets for this type of immunotherapy.

Seasonality of serum prostate-specific antigen levels: a population-based study.

OBJECTIVE: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study. METHODS: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency. RESULTS: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40). CONCLUSIONS: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced.

Sex hormone-binding globulin is a major determinant of the lipid profile: the PRIME study.

The prevalence of coronary heart disease is much higher in men than in women and sex hormones might play a role in these differences through their influence on the lipid profile. The aim of this cross-sectional study was to study the relationship between hormonal markers (total testosterone (TT), estradiol (E2), sex-hormone-binding globulin (SHBG)) and plasma lipids in a population-based sample. Subjects were 352 men, 50-59 years old, selected in France (Lille, Strasbourg and Toulouse) and Northern-Ireland (Belfast) who had questionnaires and a medical examination at baseline of the PRIME prospective study (1991-1993). Pearson correlation coefficients and Student's t tests were used to identify factors associated with plasma lipids. Multiple linear regression models were used for multivariate analyses, using triglycerides (TG) (log-transformed) and high density-lipoprotein cholesterol (HDL-C) as dependent variables. SHBG and TT were negatively correlated with TG (p<0.0001 and p<0.05, respectively) and positively correlated with HDL-C (p<0.0001 and p<0.01). E2 was positively correlated with TG (p<0.05). No significant association was found between sex-hormones and LDL-C. In multiple linear regression analyses, SHBG remained independently associated negatively with TG (p<0.01) and positively with HDL-C (p<0.0001) after adjustment for centre of recruitment, age, body mass index, systolic blood pressure, smoking, alcohol intake and physical activity. After further adjustment for insulin, the association between SHBG and HDL-C remained highly significant (p<0.0001). The association between SHBG and TG was weakened but remained also significant. Our results suggest that SHBG might to be a central protein in the hormonal regulation of the lipid profile.

Alcohol intake and diet in France, the prominent role of lifestyle.

AIM: Moderate alcohol intake is related to a decrease of coronary heart disease. This protective effect may be attributed to ethanol but may also depend on the type of alcoholic beverages. However, these differences may be confounded by lifestyle and diet. We investigated the relationships between alcohol consumption, beverage type preference and socio-economic status, diet and lifestyle. METHODS AND RESULTS: A cross-sectional survey on cardiovascular risk factors and nutrition was carried out from 1995 to 1997 by the French MONICA Centres. A sample of 1110 middle-aged men (45-64 years) was randomly recruited; 12.8% of men were abstainers and 16.3% reported a consumption of #10878;60 g/d alcohol. Smoking, waist-to-hip ratio and hypertension increased along with the amount of alcohol intake. Physical activity (from 40.9% in abstainers to 23.8% in heavy drinkers, p=0.0025), educational level (from 11.9+/-4.4 to 11.1+/-3.8 years, p=0.01), socio-economic status and diet quality index (from 7.1+/-2.3 to 6.3+/-2.0, p<0.0001 after multivariate adjustment) decreased along with the increase of alcohol consumption and were higher among wine drinkers than among beer or mixed drinkers. Diet quality index was 7.1+/-1.9, 6.4+/-1.8 and 6.6+/-1.9 among wine, beer and mixed drinkers, respectively (p=0.007 after multivariate adjustment). CONCLUSION: Moderate alcohol drinkers or wine drinkers have healthy diet and behaviours compared to other drinkers or abstainers. The living area plays a significant role in the dieting behaviours.

Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas.

Primary cutaneous lymphomas have been successfully treated with interferons (IFNs), counterbalancing the T-helper 2 (Th2)-skewing state. We undertook a phase 1, open-label, dose-escalating trial of repeated intratumoral administration of TG1042 in patients with advanced primary cutaneous T-cell lymphomas (CTCLs) and multilesional cutaneous B-cell lymphomas (CBCLs). TG1042 is a third-generation, nonreplicating human adenovirus vector containing a human IFN-gamma cDNA insert. Nine patients (7 CTCL, 2 CBCL) were enrolled at the following TG1042 doses: 3 x 10(9), 3 x 10(10), and 3 x 10(11) total particles. Local clinical response was observed in 5 of 9 treated patients (3 patients with complete response [CR] and 2 patients with partial response [PR]). Out of these, 3 patients showed systemic CR with the clearance of other noninjected skin lesions. Clinical response lasted for a median of 3 months (range, 1-6 months). Adverse events were mostly of grades 1 and 2. Seven of 9 treated patients had a detectable TG1042-derived IFN-gamma message in injected lesions after the first treatment cycle. A TG1042-IFN-gamma message was also detectable after several treatment cycles. We demonstrate the induction of humoral immune response to lymphoma tumor-antigen se70-2 after treatment. Our study shows that intralesional injections of TG1042 are both safe and well tolerated.

Joint use of clinical parameters, biological markers and CAGE questionnaire for the identification of heavy drinkers in a large population-based sample.

AIMS: Alcohol consumption in France is one of the highest in the world. Factors associated with excessive alcohol drinking are numerous. However, taken separately, none of the existing clinical or biological markers of excessive alcohol intake enables an adequate identification of heavy drinkers. The aim of this cross-sectional survey was to identify socio-demographic, clinical and biological factors associated with excessive alcohol drinking, to develop a model and to assess its reliability, thus enabling the detection of heavy drinkers. METHODS: Subjects were 1619 men and 1559 women, aged 35-64 years, living in three French areas (Lille, Strasbourg and Toulouse) and randomly selected from polling lists. Socio-demographic status, lifestyle, reported alcohol intake and answers to the CAGE questionnaire (alcohol dependence) were obtained by questionnaire. A blood sample was taken for quantification of biological parameters. Men who drank 60 g of ethanol a day (g/day) or above and women who drank 30 g/day or above were classified as heavy drinkers. The reference class (RC) gathered non-drinkers and moderate drinkers together. The sample was divided into two sub-samples: the first was used to estimate the parameters of a logistic regression model (heavy drinkers vs others), and the second to assess the accuracy of this model for the identification of heavy drinkers, using receiver operating characteristic (ROC) curves. A specific analysis was performed for each gender. RESULTS: Fourteen per cent of men and 40.8% of women were non-drinkers. Nine per cent of women and 14.4% of men were heavy drinkers. Wine was the most consumed alcoholic beverage. In the univariate analyses, differences were observed between the two groups of alcohol consumers for most of the socio-demographic, clinical and biological variables considered. In the multivariate analyses, low educational level, smoking, apoprotein B, high density lipoprotein cholesterol, mean corpuscular volume (MCV), gamma-glutamyl-transferase (GGT) and the CAGE score for men, and living area, age, MCV, GGT and the CAGE score for women remained independently and significantly associated with heavy drinking. In the validation sub-sample, these models combining different types of markers enabled a good discrimination between heavy drinkers and the RC, with an area under the ROC curve of 82% for men and of 79% for women. CONCLUSIONS: In this study, socio-demographic, clinical and biological factors and the CAGE score were independently related to excessive alcohol drinking and their joint utilization in a screening model enabled a good recognition of heavy drinkers.