Body weight and comorbidity predict mortality in COPD patients treated with oxygen therapy.

The aim of this study was to investigate the association between clinical variables and all-cause and respiratory mortality in patients with chronic obstructive pulmonary disease (COPD) undergoing long-term oxygen therapy (LTOT). The authors retrospectively studied a historic cohort of 128 patients with COPD (126 males, mean age+/-SD 68.9+/-9.7 yrs, body mass index (BMI) 25.1+/-4.5 kg.m-2, and forced expiratory volume in one second 25.4+/-8.8% predicted), who were being treated with long-term oxygen therapy in a tertiary teaching hospital between 1992 and 1999. Comorbidity, assessed with the Charlson Index, was present in 38% of the patients. Vital status and cause of death were assessed through the population death registry. A total of 78 patients (61%) had died by the end of follow-up. Three-year survival was 55%. Death was due to respiratory causes in 77% of cases. On Cox analysis, BMI<25 kg.m-2, comorbid conditions, age>or=70 yrs and cor pulmonale were associated with all-cause mortality. The BMI and comorbidity were the only significant predictive factors when the analysis was restricted to respiratory mortality. In conclusion, body mass index<25 kg.m-2 and comorbidity were predictors of all-cause and respiratory mortality in a cohort of chronic obstructive pulmonary disease patients treated with long-term oxygen therapy. These factors should be taken into account when considering the management and prognosis of these patients.     

Direct intracavernous obliteration of high-flow carotid-cavernous fistulas

Four cases of high-flow carotid-cavernous sinus fistula (CCF), three of them posttraumatic and one spontaneous, have been treated by a direct surgical approach to the cavernous sinus. The CCF's were obliterated by the introduction into the cavernous sinus of muscle fragments and/or fibrin sealant. In the three cases with a preoperatively patent internal carotid artery (ICA), the CCF was occluded and the ICA flow preserved. One of these also had a posttraumatic false aneurysm that enclosed the two avulsed ends of a transected intracavernous ICA. This was treated by cervical ICA ligation following resolution of the CCF. A fourth patient, who had previously undergone an unsuccessful ICA trapping procedure elsewhere, also obtained a good result. The case histories and the surgical technique are presented. Direct intracavernous obliteration with muscle fragments and fibrin sealant fulfills the criteria for treatment of high-flow CCF's: occlusion of the arteriovenous fistula and preservation of the ICA circulation. While this surgical technique is a therapeutic option in some cases, it appears to have precise indications in others.     

Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment

Hypoxia is related to poor prognosis because it is associated to chemo-and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia.     

IFN-alpha-induced murine B16 melanoma cancer vaccine cells: induction and accumulation of cell-associated IL-15.

Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and natural killer (NK) cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Long-term IFN-alpha treatment of B16alpha vaccine cells induced both interleukin-15 (IL-15) mRNA and IL-15 protein. The bulk of the induced IL-15 remained cell associated, either cytoplasmic or associated with the cell membrane. Immunofluorescence microscopy studies showed that the cell-associated IL-15 was broadly distributed throughout the cytoplasm. These observations suggest that long-term IFN-alpha treatment may induce primarily the truncated isoform of IL-15. Vaccination with irradiated B16alpha vaccine cells may promote tumor immunity by releasing high levels of cell-associated IL-15 when spontaneously lysed or directly killed by innate immune cells. The release of accumulated cell-associated IL-15 may then trigger a host T cell response to tumor antigens and cause host development of immunity to the B16 tumor cells.     

Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.     

Impact of a specialized outpatient heart failure follow-up program on hospitalization frequency and functional status of patients with advanced heart failure.

BACKGROUND: High rates of morbidity and mortality are observed in patients with advanced heart failure (AHF). AHF is now considered the most costly syndrome in cardiology owing to the substantial economic burden associated with hospitalizations for acute decompensation. A management program that involves specialized follow-up by a multidisciplinary team has been suggested as a desirable strategy for improving outcomes for these patients. ObjectivE: To evaluate the impact of a specialized outpatient heart failure (HF) follow-up program for patients with AHF on frequency and duration of hospitalization for HF and functional status. METHODS: We retrospectively studied 167 consecutive patients with AHF who were referred to the outpatient HF follow-up program in our institution between January and November 2002, of whom 147 followed for > or =30 days were included in the analysis. In addition to demographic and baseline clinical characteristics, HF medication and NYHA functional class, the number and duration of hospitalizations for HF during the previous 12 months were recorded and compared at the time of referral and after a follow-up period of 6.5+/-3 months. RESULTS: Of the 147 patients analyzed (aged 60.8+/-13 years; 79% male; left ventricular ejection fraction 27+/-11%), 67% were in NYHA functional class III, 20% in class II and 13% in class IV at the time of referral. There was a significant improvement in functional class during the mean follow-up period: 55% of the patients were in class III, 37% in class II, 5% in class I and 3% in class IV (p<0.0001). The proportion of patients on beta-blockers or spironolactone increased from 33% and 51% at the time of referral to 69% and 71% respectively after referral (p<0.0001). In the 12 months before referral, 39% of the patients had been hospitalized for acute decompensation of HF (87 hospitalizations - mean 7.2/month) versus 13% of the patients during the mean follow-up period (25 hospitalizations - 3.8/month, p<0.0001). No significant differences were found in the proportion of patients on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, digoxin or diuretics, or in the mean duration of hospitalization before and after referral. ConclusioN: The specialized follow-up of patients with AHF by a team with expertise in HF resulted in significant therapeutic optimization. Increased use of beta-blockers and spironolactone was associated with significant improvement in functional capacity and significant reduction in hospitalizations.