Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0–9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p  = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.

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Remodeling, diastolic dysfunction, and arterial stiffness are some of the alterations through which obesity affects the cardiovascular system. Fibrosis and inflammation are important mechanisms underlying cardiovascular remodeling, although the precise promoters involved in these processes are still unclear. Galectin-3 (Gal-3) induces inflammation and fibrosis in the cardiovascular system. We have investigated the potential role of Gal-3 in cardiac damage in morbidly obese patients, and we have evaluated the protective effect of the Gal-3 inhibition in the occurrence of cardiovascular fibrosis and inflammation in an experimental model of obesity. Morbid obesity is associated with alterations in cardiac remodeling, mainly left ventricular hypertrophy and diastolic dysfunction. Obesity and hypertension are the main determinants of left ventricular hypertrophy. Insulin resistance, left ventricular hypertrophy, and circulating levels of C-reactive protein and Gal-3 are associated with a worsening of diastolic function in morbidly obese patients. Obesity upregulates Gal-3 production in the cardiovascular system in a normotensive animal model of diet-induced obesity by feeding for 6 weeks a high-fat diet (33.5% fat). Gal-3 inhibition with modified citrus pectin (100 mg/kg per day) reduced cardiovascular levels of Gal-3, total collagen, collagen I, transforming and connective growth factors, osteopontin, and monocyte chemoattractant protein-1 in the heart and aorta of obese animals without changes in body weight or blood pressure. In morbidly obese patients, Gal-3 levels are associated with diastolic dysfunction. In obese animals, Gal-3 blockade decreases cardiovascular fibrosis and inflammation. These data suggest that Gal-3 could be a novel therapeutic target in cardiac fibrosis and inflammation associated with obesity.