Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II

Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.     

Fibrinogen as a predictor of mortality after acute myocardial infarction: a forty-two-month follow-up study.

BACKGROUND: Several studies suggest that fibrinogen may be considered an independent risk factor for coronary artery disease, but it is still on debate if we need its evaluation during an acute myocardial infarction (AMI) to prevent future fatal or non-fatal cardiovascular events. Therefore, we decided to investigate this field. METHODS: We studied 92 male patients with AMI, evaluating at admission age, body mass index, systolic blood pressure, cigarette smoking, ejection fraction, plasma levels of total cholesterol, triglycerides, fibrinogen, glycemia, and white blood cell count. All patients were followed up for 42 months to evaluate total mortality and cardiovascular morbidity. RESULTS: During the follow-up 5 patients died and 64 had one or more non-fatal cardiovascular events: angina (n = 78), heart failure (n = 17), re-AMI (n = 3), stroke (n = 3), or revascularization procedure (n = 16). A multivariate analysis revealed that fibrinogen plasma levels at admission (r = +0.213, p < 0.05) were independently associated with mortality, while systemic thrombolysis was negatively associated (r = -0.447, p < 0.0001). CONCLUSIONS: Plasma fibrinogen levels were the only independent predictor of mortality in a 42-month follow-up post-AMI. This finding, together with other observations from recent studies, suggest that fibrinogen evaluation during AMI may be useful in identifying patients at higher risk of acute event recurrence.     

Influence of left ventricular mass,uremia and hypertension on vagal tachycardic reserve

BACKGROUND: Left ventricular (LV) hypertrophy, arterial hypertension and end-stage renal disease (ESRD) are associated with deranged cardiac parasympathetic regulation and increased cardiovascular risk. These conditions often co-exist but little is known about the relative contribution of LV mass, arterial blood pressure and ESRD to impaired cardiac vagal tone.We evaluated the vagal tachycardic reserve (VTR) in subjects with normal renal function (age 58.4 +/- 6.6 years, n = 19) and in patients under chronic hemodialysis (HD) (age 62.6 +/- 13.2 years, n = 30) having wide ranges of LV mass and blood pressure. METHODS: VTR was estimated from the tachycardic response to atropine (15 microg/kg intravenously) administered during a dipyridamole-atropine stress-echo test performed as part of the diagnostic work-up for identification of inducible myocardial ischemia. LV hypertrophy (defined as LV mass index > 125 g/m2 in both genders) was present in 20 HD patients and in nine control patients. Only patients free of inducible myocardial ischemia were included in the study. RESULTS: The atropine-mediated tachycardia was: (i) significantly smaller in HD patients than in control patients (34.7 +/- 7.6 versus 60.8 +/- 10.5 beats/min, P < 0.01); (ii) independently and inversely related to LV mass (multiple regression; partial coefficients, -0.139 in HD patients and -0.382 in controls, both P < 0.01) and to mean blood pressure (-0.171 in HD patients and -0.268 in controls, both P < 0.01). CONCLUSIONS: LV mass is the strongest (inverse) determinant of VTR. Blood pressure as well as the patient's renal status are also independent correlates of VTR, and the concomitance of LV hypertrophy and ESRD exacerbates the impairment of VTR.     

Low-intensity oral anticoagulant plus low-dose aspirin during the first six months versus standard-intensity oral anticoagulant therapy after mechanical heart valve replacement: a pilot study of low-intensity warfarin and aspirin in cardiac prostheses (LIWACAP).

The objective of this study was to evaluate the safety and efficacy of low-intensity warfarin treatment plus aspirin during the first 6 months after surgery in patients undergoing heart valve substitution with mechanical prostheses. Vitamin K antagonists (VKA) are able to reduce but not eliminate thrombosis and systemic embolism in patients with mechanical heart valves. The intensity of treatment and additional use of aspirin in these patients is still controversial. Consecutive patients undergoing aortic or mitral valve replacement (or a combination of the two) with mechanical prostheses were invited to participate in the study. After stratifying for site of prosthesis, patients were randomized to receive low intensity VKA treatment (target INR 2.5) plus aspirin (100 mg/day) for the first six months (Group A) or standard-intensity (INR target 3.7) VKA treatment (Group B). Mean follow-up was 1.5 years. Principal outcome events were systemic embolism, major bleeding, and vascular death. A total of 94 patients in Group A and 104 in Group B were randomized and followed up for 144 and 163 patient years, respectively. There were 5 (5%) events in Group A (4 major bleeding events and 1 vascular death) and 4 (4%) in group B (2 major bleeding events and 2 ischemic stroke). All the events except 1 occurred within the first 6 months after surgery. Cumulative incidence of primary outcome events was 5.8% (95% CI 0.9 to 10.7) in Group A and 4.3% (95% CI 0.2 to 8.4) in Group B (p=0.6). Low-intensity treatment plus aspirin during the first six months after surgery appears to be as effective and safe as moderate-high-intensity anticoagulation.     

Clinical application of the 24-H urinary C-peptide excretion rate and its relationship to metabolic control in diabetics

Summary In this study, we evaluated in normal subjects, insulin-dependent (IDD) and non-insulin-dependent (NIDD) diabetics, the diurnal urinary C-peptide excretion rate (CPR-U) and its relationship to serum C-peptide concentration and glucose:C-peptide molar ratio, and to the common parameters of metabolic control. The CPR-U (and CPR-U/g creatinine) were significantly lower in IDD and higher in NIDD compared to control subjects. Moreover, a good and significant correlation with serum C-peptide concentrations and the glucose:C-peptide ratio in diabetic subjects as well as in controls and diabetics considered together was found. A slight but significant correlation was present in diabetic subjects between CPR-U and body mass index (r=0.45), 24-h glycosuria (r=−0.36), HbA1 levels (r=−0.31), post-prandial glucose concentrations (r=−0.26) and per cent glucose variation after each meal (r=−0.34). No differences were found in CPR-U and the degree of metabolic control between obese and non-obese NIDD. In conclusion, CPR-U may be a useful and simple method of defining the secretory activity of the B-cell. Metabolic control in diabetics is slightly correlated to the degree of B-cell function as evaluated by the diurnal excretion rate of C-peptide in urine. Part of this paper was presented at the National Meeting of the Italian Diabetes Association, Bari, May 27–29, 1982.     

The Perugia hospital-based Stroke Registry: report of the 2nd year

This study reports the characteristics of stroke patients admitted to our hospital in the period Jan 1st, 1998-Dec 31st 1999. Seven hundred and ninety seven consecutive subjects (412 males; mean age 71 +/- 13 years) with a first-ever stroke were registered. Two-thirds of patients (65%) were admitted to the Stroke Unit (SU). The remaining part was managed in six general medicine wards (GM) or other services [neurosurgery and intensive care units (ICU+ NS)]. Ischemic stroke occurred in 534 subjects (67%). The high prevalence (30.1%) of haemorrhages can be partly explained by the presence of specialized neurosurgical services. Athero-thrombotic infarctions occurred in 21.7% of patients, lacunar in 24.7%, cardioembolic in 18.1%, other determined in 6.1%, and other undetermined in 27.5%. Overall hospital mortality was 10%. In cerebral hemorrhage mortality was 18% (44/240) vs. 6.3% (32/534) in ischemic stroke (p < 0.05). The distribution of stroke types and mortality was similar to other previous reports.     

Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients

BACKGROUND: In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. METHODS: A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). RESULTS: Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). CONCLUSIONS: Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.     

Inherited thrombophilia and gestational vascular complications

The most common causes of inherited thrombophilia, the factor V Leiden and the factor II A20210 mutations, confer a higher risk of venous thromboembolism. Moreover, several studies have suggested that they can have a role in the occurrence of gestational vascular complications in otherwise unexplained recurrent fetal losses, hypertensive disorders of pregnancy and fetal growth restriction. Observational and case-control studies addressing these issues are available in literature. However, longitudinal, perspective studies are lacking. Mild hyperhomocysteinaemia can be due partly to inherited susceptibility--as the homozygous carriership of the T677 variant in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR). Case-control studies have been carried out on a possible association between unexplained fetal losses and mild hyperhomocysteinaemia. Although case-control and perspective studies are available on hyperhomocysteinaemia and other gestational vascular complications the data are conflicting.Intervention studies have been carried out to prevent adverse obstetric outcomes in women with factor V Leiden or factor II A20210 mutations and previous adverse outcomes. Although these are not randomized controlled trials, all have found significantly better outcomes in treated pregnancies compared to those of untreated pregnancies in the same women.