Hemodynamic and angiographic results following surgical correction of mitral insufficiency. Apropos of 51 repeated catheterizations

The benefits of surgical correction of mitral incompetence were assessed in 51 patients by comparing pre and postoperative catheter and quantitative angiographic results. The mean age of the patients was 43.5 +/- 12.3 years. The mitral lesions were elongation or ruptured chordae (27 cases), valvular perforation due to endocarditis (1 case) and the usual rheumatic disease in 23 cases. Hemodynamic investigation was carried out on average 2 months before operation and 29 +/- 22 months after surgery. The following angiographic parameters were measured : indexed end diastolic and end systolic volumes (EDV and ESV), ejection fraction (EF), myocardial mass (MM) and its ratio to EDV (hypertrophy coefficient : HC) and the geometry of the ventricle as assessed by diastolic and systolic coefficients of excentricity (DE and SE). Surgery comprised 13 mitral valvuloplasties and 38 valve replacements. Patients who suffered perioperative myocardial infarction or who had a residual valvular lesion were excluded from the study. After surgery, the hemodynamic state was considerably improved with a significant decrease in pulmonary capillary pressures (11 +/- 5 compared to 17 +/- 6 mmHg, p less than 0.09) and mean pulmonary artery pressures (19 +/- 7 compared to 27 +/- 11, p less than 0.01) and increase in cardiac index (2.8 +/- 0.7 compared to 2.3 +/- 0.6 l/min/m2, p less than 0.01). There was an associated decrease in ventricular volumes (EDV : 115 +/- 44 compared to 165 +/- 43, p less than 0.01) (ESV : 60 +/- 39 compared to 77 +/- 22, p less than 0.001). The reduction in myocardial mass was less spectacular (129 +/- 40 compared to 148 +/- 32, p less than 0.01) with a resulting increase in the HC (1.10 +/- 0.26 compared to 0.88 +/- 0.17, p less than 0.001). The geometry of the LV was less spherical in diastole (DE 0.76 +/- 0.08 compared to 0.70 +/- 0.08, p less than 0.001) and in systole (SE = 0.83 +/- 0.06 compared to 0.77 +/- 0.08, p less than 0.001). The EF fell slightly but this was not statistically significant (0.51 +/- 0.13 compared to 0.53 +/- 0.09 NS). The surgical result of 14 patients with PCP greater than or equal to 13 mmHg was considered hemodynamically incomplete, and this was confirmed by a lower cardiac index than in the remaining 37 patients (2.4 +/- 0.5 compared to 3.0 +/- 0.7, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)     

The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis

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Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a common adverse effect of unfractionated heparin (UFH) therapy. In contrast, only a few patients have been reported with HIT following low-molecular-weight heparin (LMWH) therapy (LMW-HIT). To define the clinical and biological characteristics of LMW-HIT, 180 patients treated for suspected HIT at 15 French centres were investigated. Clinical history was recorded and HIT was confirmed in 59 patients with positive serotonin release assay results: 57 of them had high levels of antibodies (Abs) to heparin-platelet factor 4 complexes (H/PF4) and two had Abs to interleukin 8. Eleven patients were treated exclusively with LMWH (LMW-HIT) and 48 with UFH either alone (UF-HIT, n = 34) or combined with LMWH (UF/LMW-HIT, n = 14). The LMW-HIT and UF-HIT groups were similar with respect to sex, age, platelet count before heparin therapy, frequency of bleeding and occurrence of disseminated intravascular coagulation. The interval to onset of HIT was longer in LMW-HIT patients compared with UF-HIT patients (P = 0.03). Severe thrombocytopenia (platelets < 15 x 10(9)/l) was more frequent in the LMW-HIT group (P = 0.04). Thrombosis occurred in three of 11 LMW-HIT patients, i.e. as frequently as in UF-HIT patients. LMW-HIT is potentially severe and may be observed after longer heparin treatment compared with UF-HIT. It is highly recommended, therefore, that platelet counts be monitored carefully whenever LMWH is administered.     

Limited treatment adaptation despite poor asthma control in asthma patients treated with inhaled corticosteroids

Objective: Current asthma guidelines recommend use of inhaled corticosteroids (ICS) in patients with persistent disease. This study was designed to investigate (1) the proportion of patients prescribed ICS-containing maintenance treatment who achieve asthma control, (2) determinants of control and (3) how physicians adapt treatment to the level of control. Methods: General practitioners (GPs) and chest physicians (CPs) in France recruited patients consulting for asthma and prescribed an ICS. Over a 2-year follow-up period, asthma symptoms in the previous 3 months and treatments prescribed were documented at each visit. Variables independently associated with asthma control were determined by multiple logistic regression. Results: Data were available for 924 patients recruited by GPs and 455 recruited by CPs. Asthma control was acceptable in only 24% of patients at inclusion, and in 33.6% at the last follow-up visit. Five factors were independently associated with asthma control: age (or time since diagnosis), gender, smoking status, allergic aetiology of asthma and treatment. Most patients (56.3%) were prescribed the same ICS dose regimen at the end of follow-up as at inclusion. The intensity of controller therapy had been increased in only 12.2% of patients unacceptably controlled at inclusion. Conclusions: Asthma was unacceptably controlled in most patients receiving ICS-containing maintenance treatment and remained so during follow-up. Despite this, treatment adaptations by GPs and CPs were very infrequent. This unsatisfactory situation may be improved by adopting a more dynamic approach to tailoring controller therapy to the needs of the patient.     

Impact of Direct Transcatheter Aortic Valve Replacement Without Balloon Aortic Valvuloplasty on Procedural and Clinical Outcomes: Insights From the FRANCE TAVI Registry

Objectives

This study sought to describe the current practices and compare outcomes according to the use of balloon aortic valvuloplasty (BAV) or not during transcatheter aortic valve replacement (TAVR).

p16 gene homozygous deletions in acute lymphoblastic leukemia

The p16 protein is a cyclin inhibitor encoded by a gene located in 9p21, which may have antioncogenic properties, and is inactivated by homozygous p16 gene deletion or, less often, point mutation in several types of solid tumors often associated to cytogenetic evidence of 9p21 deletion. We looked for homozygous deletion and point mutation of the p16 gene in acute lymphoblastic leukemia (ALL), where 9p21 deletion or rearrangement are also nonrandom cytogenetic findings. Other hematologic malignancies including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), chronic lymphocytic leukemia (CLL), and myeloma were also studied. Homozygous deletion of the p16 gene was seen in 9 of the 63 (14%) ALL analyzed, including 6/39 precursor B-ALL, 3/12 T-ALL, and 0/12 Burkitt's ALL. Three of the 7 ALL with 9p rearrangement (including 3 of the 5 patients where this rearrangement was clearly associated to 9p21 monosomy) had homozygous deletion compared to 5 of the 55 patients with normal 9p (the last patient with homozygous deletion was not successfully karyotyped). Single stranded conformation polymorphism analysis of exons 1 and 2 of the p16 gene was performed in 88 cases of ALL, including the 63 patients analyzed by Southern blot. Twenty-six of the cases had 9p rearrangement, associated to 9p21 monosomy in at least 12 cases. A missense point mutation, at codon 49 (nucleotide 164), was seen in only 1 of the 88 patients. No homozygous deletion and no point mutation of the p16 gene was seen in AML, MDS, CLL, and myeloma. Homozygous deletion of interferon alpha genes (situated close to p16 gene in 9p21) was seen in only 3 of the 9 ALL patients with p16 gene homozygous deletion, and none of the ALL without p16 gene homozygous deletion. Our findings suggest that homozygous deletion of the p16 gene is seen in about 15% of ALL cases, is not restricted to cases with cytogenetically detectable 9p deletion, and could have a pathogenetic role in this malignancy. On the other hand, p16 point mutations are very rare in ALL, and we found no p16 homozygous deletions or mutations in the other hematologic malignancies studied.     

TIMI risk score underestimates prognosis in unstable angina/non-ST segment elevation myocardial infarction

OBJECTIVES: To determine the value of the TIMI risk score in the individual risk stratification of patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: TIMI risk score is a validated tool to identify groups of patients at high risk for major cardiac events. Its prognostic value in individual patients with current diagnostic tools and therapy is unknown. METHODS: TIMI risk score was assessed in patients with UA/NSTEMI admitted to six Belgian hospitals and related to clinical outcome at 30 days. RESULTS: Of the 500 patients enrolled, 49.4% were placed in the low TIMI risk group (score = 0-3) and 50.6% in the high-risk group (score = 4-7). Multivariate analysis identified raised cardiac markers and invasive strategy, but not high TIMI risk score as independent predictors of death and new myocardial infarction (MI). Moreover, the incidence of death and MI in the low TIMI risk group with positive cardiac markers was not lower than in the high TIMI risk group with positive markers: 15.1% versus 17.8% (P = 0.7). CONCLUSIONS: TIMI risk score is of limited value for individual risk stratification. The presence of positive cardiac markers (troponin) appears to be a more powerful prognostic marker.     

Inefficacy of infliximab in primary Sjögren's syndrome: results of the randomized, controlled Trial of Remicade in Primary Sjögren's Syndrome (TRIPSS)

OBJECTIVE: There is no effective treatment for patients with primary Sj?gren's syndrome (SS). Since tumor necrosis factor alpha (TNF alpha) could be a key element in the pathogenesis of primary SS, we conducted a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of infliximab in primary SS. METHODS: A total of 103 patients with primary SS were randomly assigned to receive infliximab infusions (5 mg/kg) or placebo at weeks 0, 2, and 6 and were followed up for 22 weeks. All patients fulfilled the new American-European Consensus Group criteria for SS and had active disease as assessed by values >50 mm on 2 of 3 visual analog scales (VAS) (0-100 mm) that evaluated joint pain, fatigue, and buccal, ocular, skin, vaginal, or bronchial dryness. A favorable overall response was defined as the patient having > or =30% improvement between weeks 0 and 10 in the values on 2 of the 3 VAS. Secondary end points were values on each VAS separately, the number of tender and swollen joints, the basal salivary flow rate, results of the Schirmer test for lacrimal gland function, the focus score on labial salivary gland biopsy, the level of C-reactive protein, and the erythrocyte sedimentation rate evaluated at weeks 0, 10, and 22, as well as quality of life evaluated by use of the generic Short Form 36 questionnaire administered at weeks 0, 10, and 22. RESULTS: At week 10, 26.5% of patients receiving placebo and 27.8% of patients treated with infliximab had a favorable overall response (P = 0.89), and at week 22, 20.4% of the placebo group and 16.7% of the infliximab group had a favorable response (P = 0.62). In addition, the 2 groups did not differ in any of the secondary end points over the 22 weeks of the trial. Severe adverse events reported in the infliximab group did not differ from those observed in previous studies. CONCLUSION: This randomized, double-blind, placebo-controlled study of an anti-TNF agent did not show any evidence of efficacy of infliximab in primary SS.     

Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase

In chronic myelogenous leukemia (CML) imatinib mesylate has been shown to selectively inhibit the tyrosine kinase domain of the oncogenic bcr-abl fusion protein. Using this agent alone high rates of cytogenetic responses were recorded. However, several mechanisms of resistance have been described. In vitro studies examining the effects of imatinib mesylate plus cytarabine have shown synergistic antiproliferative effects of this combination. Thus, the CML French Group decided to perform a phase 2 trial testing a combination of imatinib mesylate and low-dose cytarabine in 30 previously untreated patients in chronic phase. Treatment was administered on 28-day cycles. Patients were treated continuously with imatinib mesylate orally at a dose of 400 mg daily. Cytarabine was given on days 15 to 28 of each cycle at an initial dose of 20 mg/m2/d via subcutaneous injection. Adverse events were frequently observed with grade 3 or 4 hematologic toxicities and nonhematologic toxicities in 53% (n = 16) and 23% (n = 7) of patients, respectively. The cumulative incidence of complete cytogenetic response (CCR) at 12 months was 83% and at 6 months 100% of the patients achieved complete hematologic response (CHR). We concluded that the combination was safe and promising given the rates of response.