One-year prognosis of primary ventricular fibrillation complicating acute myocardial infarction. The GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico) investigators

The 1-year prognosis of 293 patients discharged alive from the hospital after acute myocardial infarction (AMI), who experienced primary ventricular fibrillation (VF) in the acute phase, was compared with that of a reference group of 6,337 patients identified from the same population included in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto miocardico (GISSI) trial. There was no difference in the 6- and 12-month mortality between the patients with primary VF and the reference group (3.7 vs 2.7% and 4.1 vs 4.2%, respectively). Survival of the 2 groups was also similar when patients were stratified according to infarct site (anterior and posterior), and whether or not they received treatment with streptokinase during AMI. Thus, long-term mortality of patients discharged alive after AMI complicated by primary VF is low and is not influenced by previous fibrinolytic therapy or by infarct site. The excess mortality of patients with primary VF is confined to the hospital phase, after which survivors represent a low-risk subgroup.     

Clinical characteristics, treatment outcome and survival of 36 adult patients with primary anaplastic large cell lymphoma. Gruppo Italiano per lo Studio dei Linfomi (GISL).

BACKGROUND AND OBJECTIVE: Although in recent years anaplastic large-cell lymphoma (ALCL) has emerged as a distinct clinico-pathological entity, a gold standard for treatment has still not been defined. Goals of our histologic, phenotypic and clinical study were to present clinical findings, treatment outcome and survival rates of a small, but highly homogeneously treated, series of patients. DESIGN AND METHODS: From April 1991, 36 newly diagnosed adult patients with systemic ALCL CD30+, entered a prospective non-randomized trial in one of the institutions participating in a GISL (Gruppo Italiano per lo studio dei Linfomi) study and were treated with a MOPP/EBV/CAD hybrid scheme. Chemotherapy (CHT) was administered every 28 days, for a total of 6 cycles. After CHT, 19 patients received radiation therapy (RT) to the site of previously involved fields. Kaplan and Meier and log-rank tests were used for statistical analysis. RESULTS: The overall complete remission rate was 78%, the partial remission rate was 6%. The overall survival rate at 74 months was 69%. No statistically significant differences in response or survival rates were noted comparing ALCL-HL and -CT subgroups, T+ Null- and B- subtypes, or ALCL-HL and -CT, with different phenotypes. In the analysis of patients with T+ Null phenotype treated with CHT+RT in comparison with B-ALCL patients who had the same treatment, we observed statistically significant differences in the survival rate (p=0.048). No prognostic factors predictive of response or survival were identified. INTERPRETATION AND CONCLUSIONS: Our results show that using MOPP/ABV/CAD the results, in terms of remission rate and survival, are similar to those obtained with 3rd generation CHT regimens. The diagnosis of T and Null ALCL is the most important prognostic factor, because it is associated with a very good survival, even in patients with a high prognostic index. Finally, we believe that longer follow-ups are needed to evaluate long-term survival and toxicity with different treatments.     

Tuberculosis in HIV-infected subjects in Italy: a multicentre study. The Gruppo Italiano di Studio Tubercolosi e AIDS.

OBJECTIVES: To evaluate the strength of the association between tuberculosis and HIV infection in Italy, to assess the pattern of this association in relation to HIV transmission categories, and to describe clinical presentation of tuberculosis in a large group of Italian HIV-infected subjects. DESIGN: Multicentre review of clinical records. SETTING: Twenty-one infectious disease hospital units in nine of the 20 administrative regions of Italy. PATIENTS, PARTICIPANTS: All HIV-infected adults observed by each participating unit (in- and outpatients) between 1985 and 1989. MAIN OUTCOME MEASURE: Culture-proven tuberculosis. RESULTS: A total of 306 cases of tuberculosis were observed. Of these, 85 were pulmonary, 167 extrapulmonary, and 54 both pulmonary and extrapulmonary. The proportion of HIV-infected subjects diagnosed with tuberculosis increased during the study period from three out of 1380 (0.2%) in 1985 to 152 out of 6504 subjects (2.3%) in 1989 (P less than 0.0001). Two hundred and twenty-six of the 2760 (8.19%) patients with AIDS had tuberculosis within 12 months of AIDS diagnosis; the proportion of AIDS patients with tuberculosis remained stable after 1985. Compared with AIDS patients who were intravenous drug users, only homosexual AIDS patients had a significantly lower proportion of tuberculosis (178 out of 1958 versus 30 out of 522; P less than 0.02). CONCLUSIONS: Our data show that tuberculosis is quite common among HIV-infected subjects in Italy, and suggest that the risk of tuberculosis in these subjects has not changed. There are some differences between the pattern of the association between tuberculosis and HIV infection in Italy, compared with other industrialized countries.     

Effect of streptokinase on left ventricular modeling and function after myocardial infarction: the GISSI (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico) Trial

It has been shown that streptokinase administration at the time of acute myocardial infarction reduces mortality significantly, and that this reduction in mortality should be related to salvage of jeopardized myocardium and preservation of left ventricular function. To better define the relation between thrombolytic therapy and left ventricular modeling and function after acute myocardial infarction, 331 consecutive patients enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico trial were studied by two-dimensional echocardiography just before discharge from the hospital. A 6 month follow-up examination was also available in 232 of these patients. Ventricular volumes were computed from an apical four chamber view, according to a previously published algorithm. An infarct size index was also semiquantitatively assessed, according to the number of akinetic and dyskinetic segments in an 11 segment left ventricular model. At predischarge examination, the 161 patients assigned to streptokinase treatment showed smaller ventricular volumes (end-diastolic volume 119.3 +/- 49.7 versus 134.5 +/- 57.8 ml [p = 0.011]; end-systolic volume 65.4 +/- 36.4 versus 74.9 +/- 45.7 ml [p = 0.036]) and smaller regional wall motion index (2.2 +/- 1.9 versus 2.7 +/- 1.9 segments; p = 0.019) compared with values in the 170 patients assigned to standard care; there was no difference in ejection fraction (46.6 +/- 14.1 versus 45.9 +/- 14.9%; p = 0.64). For both groups of patients, there was a significant relation between end-systolic volume and regional wall motion index (p less than 0.001); for large and similar extents of infarct size, ventricular volume was smaller in patients assigned to thrombolytic treatment than in patients assigned to standard care. At 6 months' follow-up, the differences in volume and regional dysfunction detected at the early examination persisted: 110.8 +/- 47.6 versus 127.9 +/- 53.8 ml for end-diastolic volume (p = 0.001), 56.3 +/- 33.6 versus 69.4 +/- 42.1 ml for end-systolic volume (p = 0.001) and 1.8 +/- 1.8 versus 2.3 +/- 1.8 segments for regional wall motion index (p = 0.001). Again, for comparable extents of infarct size, end-systolic volume was smaller in patients who received streptokinase (n = 110) than in those assigned to conventional treatment (n = 122). It is concluded that streptokinase improves left ventricular modeling and function in patients with myocardial infarction, reducing the extent of regional wall motion abnormalities and lessening postinfarction ventricular dilation. The beneficial effects persist up to 6 months.     

Serum cholesterol and acute myocardial infarction: a case-control study from the GISSI-2 trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto-Epidemiologia dei Fattori di Rischio dell'Infarto Miocardico Investigators.

OBJECTIVE--To examine the role of serum cholesterol in acute myocardial infarction in a population of patients with no history of coronary heart disease and to establish the nature of this association, the degree of risk, and the possible interaction between serum cholesterol and other major risk factors for acute myocardial infarction. DESIGN--Case-control study. SETTING--90 hospitals in northern, central, and southern Italy. PATIENTS--916 consecutive cases of newly diagnosed acute myocardial infarction and 1106 hospital controls admitted to hospital with acute conditions not related to known or suspected risk factors for coronary heart disease. DATA COLLECTION--Data were collected with a structured questionnaire and blood samples were taken by venepuncture as soon as possible after admission to hospital from cases and controls. Blood cholesterol concentrations were available for 614 cases and 792 controls. RESULTS--After adjustment by logistic regression for sex, age, education, geographical area, smoking status, body mass index, history of diabetes and hypertension, and family history of coronary heart disease the estimated relative risks of acute myocardial infarction for quintiles of serum cholesterol (from lowest to highest) were 2.3 (95% confidence interval (CI) 1.6 to 3.4), 3.1 (95% CI 2.1 to 4.6), 4.1 (95% CI 2.8 to 6.0), and 5.2 (95% CI 3.5 to 7.7). The estimated relative risk across selected covariates increased from the lowest to the highest quintile of serum cholesterol particularly for men, patients under 55 years of age, and smokers. When the possible interaction of known risk factors with serum cholesterol was examined, smoking habits, diabetes, and hypertension had approximately multiplicative effects on relative risk. CONCLUSIONS--This study indicates that serum cholesterol was an independent risk factor for acute myocardial infarction. This association was linear, with no threshold level. Moreover, there was a multiplicative effect between cholesterol and other major risk factors on the relative risk of acute myocardial infarction.     

The role of high-dose therapy and autologous stem cell transplantation in patients with primary refractory Hodgkin's lymphoma: a report from the Gruppo Italiano per lo Studio dei Linfomi (GISL)

GISL recently conducted an exhaustive survey of 1078 patients with Hodgkin's Lymphoma (HL) enrolled between 1988 and 2002 in different prospective trials. Treatment failure was observed in 82 out of 1078 patients; of these 82 patients with refractory HL, complete information was available for 72, who form the evaluable population of the present study. After the initial therapy failure, 51 patients were treated with conventional salvage chemotherapy (CC) (n = 24) or high-dose chemotherapy (HDC) (n = 27); 4-year overall survival (OS) was 81% in the HDC group versus 38% in the CC group (P = 0.019). The remaining 21 patients had rapidly progressive disease and died. After a median follow-up of 2.8 years, the projected OS for all 72 patients is 58 and 49% at 3 and 5 years, respectively. Age <45 years, the absence of systemic symptoms and a PS <1 predicted a significantly longer OS. Interestingly, the majority of patients with two or three negative prognostic factors did not receive potentially curative therapy. In conclusion, HDC seems to be a reasonable option for selected patients with refractory HL, although the majority of them did not receive a transplant. Finally, patients with a high-risk score had little chance of receiving potentially curative treatment.     

Incidence and short-term prognosis of late sustained ventricular tachycardia after myocardial infarction: results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-3) Data Base.

BACKGROUND: There is little epidemiologic information from large multicenter databases on sustained monomorphic ventricular tachycardia occurring after the initial 48 hours of myocardial infarction. METHODS: We reassessed its incidence and short-term prognosis in 16,842 patients with a definite myocardial infarction enrolled in the Gruppo Italiano per lo Studio della Soprovvivenza nell'Infarto Miocardico (GISSI-3) trial. RESULTS: The incidence rate of late sustained ventricular tachycardia by 6 weeks was around 1%. Older age, a history of hypertension, diabetes, and myocardial infarction, nonadministration of lytic therapy, Killip class > I, > or = 6 leads with ST-segment elevation, higher heart rate, and bundle branch block on admission were significantly more frequent among patients with than without late sustained ventricular tachycardia. Patients with ventricular tachycardia had a more complicated course in-hospital and posthospital to 6 weeks than the reference group did. The arrhythmia was associated with a significant excess of pump failure, atrial flutter-fibrillation, asystole, atrioventricular block, ventricular fibrillation within the first 48 hours of myocardial infarction, and recurrent ischemic events. Larger left ventricular end-systolic volumes and lower ejection fractions were more frequent among ventricular tachycardia patients than in the reference group by 6 weeks. Death rates by 6 weeks were 35% for patients with ventricular tachycardia and 5% for those without the arrhythmia. Irrespective of the stratification of patients by site and type of infarct and presence/absence of bundle branch block, the occurrence of the arrhythmia was associated with reduced 6-week survival. CONCLUSION: In a proportional hazard regression model late sustained ventricular tachycardia was retained as a strong, independent predictor of 6-week mortality after myocardial infarction (hazard ratio 6.13, 95% confidence interval 4.56-8.25).     

A simple electrocardiographic predictor of the outcome of patients with acute myocardial infarction treated with a thrombolytic agent: A Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2)-derived analysis

Objectives. This analysis aimed to evaluate in a large patient cohort the relation between ST segment alterations after fibrinolytic therapy for acute myocardial infarction and 1) the combined end point of in-hospital mortality plus clinical congestive heart failure or extensive left ventricular damage, and 2) mortality 30 and 180 days after randomization.Background. Angina relief, enzyme release acceleration and ST segment normalization are related to coronary artery reperfusion and prognosis. Electrocardiographic (ECG) evaluation before and after fibrinolytic drug administration has been used to predict short-and long-term clinical outcome in acute myocardial infarction.Methods. Patients enrolled in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial underwent a standard ECG on admission and after 4 h of alteplase or streptokinase therapy; 7,426 recordings were suitable for ST segment analysis. A decrease ≥ 50% in the sum of ST segment elevation in all ECG leads was adopted as the cutoff for predicting coronary artery patency. Recanalization was deemed to have occurred in 4,951 patients (group A) versus 2,475 patients without reperfusion (group B).Results. Group A patients experienced a lower incidence of the combined end point than did group B patients (16.2% vs. 22.9%, respectively), as well as of all its components (death, clinical heart failure, ejection fraction < 35%, injured myocardial segment > 45%, QRS score > 10). Thirty- and 180-day mortality rates were lower in group A than group B (3.5% and 5.7% vs. 7.4% and 9.9%, respectively); relative risk (Cox) was 0.46 (95% confidence interval [CI] 0.37 to 0.57) for 30-day and 0.58 (95% CI 0.48 to 0.70) for 180-day mortality. Patients in group A had significantly less ventricular fibrillation and sustained ventricular tachycardia but more ischemic episodes (early recurrent angina plus myocardial infarction recurrence).Conclusions. A simple, inexpensive instrumental evaluation, unaffected by different epidemiologic and clinical characteristics of the population analyzed, can allow early assessment of the effectiveness of fibrinolytic treatment with respect to the main clinical outcomes.     

Prognostic impact of elevated serum uric acid levels on long-term outcomes in patients with chronic heart failure: A post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial

BackgroundThe prognostic impact of hyperuricemia on long-term clinical outcomes in patients with chronic heart failure (HF) has been investigated in observational registries and clinical trials, but the results have been often inconclusive. We examined the prognostic impact of elevated serum uric acid levels on long-term clinical outcomes in the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) trial.Clinical Trial Registration. ClinicalTrials.gov IdentifierNCT00336336.MethodsWe assessed the rates of all-cause death, cardiovascular death, cardiovascular hospitalization and the composite of all-cause death or cardiovascular hospitalization over a median follow-up of 3.9 years among 6683 ambulatory patients with chronic HF.ResultsPatients in the 3rd serum uric acid tertile (>7.2 mg/dl) had a nearly 1.8-fold increased risk of both all-cause death and cardiovascular death, and a nearly 1.5-fold increased risk of cardiovascular hospitalization and of the composite endpoint compared to those in the 1st uric acid tertile (<5.7 mg/dl). Beyond serum uric acid ≥ 7 mg/dl the risk of outcomes increased sharply and linearly. The significant association between elevated serum uric acid levels and adverse outcomes persisted after adjustment for multiple established cardiovascular risk factors, HF etiology, left ventricular ejection fraction, medication use and other potential confounders, with an adjusted hazard ratio of 1.37 (95% CI 1.22–1.55) for all-cause death, 1.48 (1.29–1.69) for cardiovascular death, 1.19 (1.09–1.30) for cardiovascular hospitalization and 1.21 (1.11–1.31) for the composite endpoint, respectively.ConclusionsElevated serum uric acid levels are independently associated with poor long-term survival and increased risk of cardiovascular hospitalization in patients with chronic HF.     

Guidelines of tuberculosis preventive therapy for HIV-infected persons: a prospective, multicentre study. GISTA (Gruppo Italiano di Studio Tubercolosi e AIDS).

The aim of this study was to assess the degree of implementation of national guidelines for isoniazid preventive therapy (IPT) among human immunodeficiency virus (HIV)-infected individuals and factors affecting the impact of the programme. Twenty-eight infectious disease hospital units in Italy participated in this observational, multicentre, prospective cohort study. A number of HIV-infected subjects, (n=1,705) seen for the first time as outpatients, were included in this analysis. Of the subjects considered, 1,215 out of the 1,705 completed purified protein derivative (PPD) screening. Variables independently associated with offering and completion of PPD screening included having acquired immune deficiency syndrome (AIDS), higher educational levels and currently receiving therapy. Overall, 103 subjects were identified as candidates for IPT. Of these subjects, five had tuberculosis and 15 had contraindications to IPT. Forty subjects agreed to start IPT, and 29 completed a full-course regimen. The incidence of tuberculosis among IPT candidates who either did not begin or discontinued IPT was 6.1 per 100 person-yrs, while no cases of tuberculosis were observed in subjects completing IPT. Several factors may limit the implementation of an isoniazid preventive therapy programme for human immunodeficiency virus-infected persons. Physicians fail to offer purified protein derivative screening to patients with high degrees of immunodeficiency, and those with a more intense workload seem to pay less attention to this test. The high number of contraindications among patients and their low level of acceptance further affects the impact of isoniazid preventive therapy.     

Phase II fludarabine and cyclophosphamide for the treatment of indolent B cell non-follicular lymphomas: final results of the LL02 trialof the Gruppo Italiano per lo Studio dei Linfomi (GISL)

Indolent non-follicular non-Hodgkin lymphomas (INFL) are a heterogenous subset whose treatment has been poorly investigated. In this context we have evaluated the efficacy and safety of combined fludarabine and cyclophosphamide (FC) upfront therapy. Sixty-three patients with advanced INFL were enrolled in the study. Therapy consisted in FC combination (25 and 250?mg/m², i.v., respectively, for three consecutive days) every 28?days for six courses. After histological review, 61 patients (36 men, median age 64?years, range 40?C70?years) were evaluated (22 small lymphocytic, 11 lymphoplasmacytic, 25 marginal zone and 3 CD5-negative non-Hodgkin lymphomas not otherwise specified). Further two patients were excluded for lack of essential data; six patients were withdrawn before the third cycle because of WHO grade III and IV toxicity. At the final evaluation, the overall response rate was 83% with 40.7% of complete remission. Intention-to-treat analysis showed that at the median follow-up of 36?months, overall survival, progression-free survival and failure-free survival were respectively 78%, 60% and 46%; remission duration among the 49 patients achieving complete remission/partial remission at the end of treatment was 65% (44?C78) without significant differences between the main histotypes. The most frequent grade III and IV toxic events were haematological (neutropaenia 34%, anaemia 18% and thrombocytopaenia 11%) and infectious (10%). FC is effective for advanced untreated INFL. Early deaths and haematological toxicity suggest careful patient selection and monitoring.     

Segmental colitis associated with diverticula: a prospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII)

OBJECTIVE: Little is known about the clinical features and natural history of segmental colitis associated with diverticula. Our aim was to evaluate the incidence of segmental colitis associated with diverticula in patients undergoing colonoscopy, its clinical picture, and its outcome. METHODS: This was a multicenter, prospective study. Patients with inflammatory bowel disease (IBD)-like lesions limited to colonic segments with diverticula were enrolled. Patients were treated with oral and topical 5-aminosalicylic (5-ASA) until remission was achieved; clinical and endoscopic follow-up was planned at 6 wk and 12 months. RESULTS: A total of 5457 consecutive colonoscopies were recorded at five participating institutions; 20 patients (0.36%) met the endoscopic criteria for segmental colitis associated with diverticula. All had lesions in the left colon, and one also had lesions in the right colon. In six cases, a specific diagnosis was made thereafter. The remaining 14 patients (0.25% of colonoscopies; eight men; age range, 49-80 yr) were in clinical and endoscopic remission at the first follow-up visit. At onset, 13/14 had hematochezia, seven had diarrhea, and five had abdominal pain; only one had weight loss. No subject had fever. In all but one case, blood chemistries were normal. Five patients had had similar symptoms previously. Thirteen of 14 patients were in clinical and endoscopic remission at 12 months. CONCLUSIONS: This endoscopic picture is not an exceptional finding. Hematochezia was the main clinical feature, and no relation with gender, age, or smoking habit was found. Blood chemistries were generally normal and the rectum was spared. The histological features were not diagnostic and most patients did not complain of any abdominal symptoms 12 months after enrollment.     

The natural history of ulcerative proctitis: a multicenter, retrospective study. Gruppo di Studio per le Malattie Infiammatorie Intestinali (GSMII)

OBJECTIVE: The aim of this study was to evaluate the clinical features and the long term evolution of patients with a well defined initial diagnosis of ulcerative proctitis. METHODS: Patients with an original diagnosis of ulcerative proctitis who had been seen at any of 13 institutions from 1989 to 1994 were identified. Data on disease onset and subsequent evolution were recorded. In addition, 575 patients with more extensive disease, treated in the same centers, were used as controls. RESULTS: A total of 341 patients satisfied the inclusion criteria. The percentage of smokers in these patients was slightly lower than in controls; no differences were found in the other clinical/demographic variables evaluated. A total of 273 patients entered long term follow-up (mean, 52 months). Proximal extension of the disease occurred in 74 of them (27.1%). The cumulative rate of proximal extension and of extension beyond the splenic flexure was 20% and 4% at 5 yr and 54% and 10% at 10 yr, respectively. The risk of proximal extension was higher in nonsmokers, in patients with >3 relapses/yr, and in patients needing systemic steroid or immunosuppressive treatment. Refractory disease was confirmed as an independent prognostic factor at multivariate analysis. CONCLUSIONS: Proximal extension of ulcerative proctitis is frequent and may occur even late after the original diagnosis. However, the risk of extension beyond the splenic flexure appears to be quite low. Smoking seems to be a protective factor against proximal extension, whereas refractoriness is a risk factor for proximal extension of the disease.