Prognostic and biologic significance of chromosomal imbalances assessed by comparative genomic hybridization in multiple myeloma

Cytogenetic abnormalities, evaluated either by karyotype or by fluorescence in situ hybridization (FISH), are considered the most important prognostic factor in multiple myeloma (MM). However, there is no information about the prognostic impact of genomic changes detected by comparative genomic hybridization (CGH). We have analyzed the frequency and prognostic impact of genetic changes as detected by CGH and evaluated the relationship between these chromosomal imbalances and IGH translocation, analyzed by FISH, in 74 patients with newly diagnosed MM. Genomic changes were identified in 51 (69%) of the 74 MM patients. The most recurrent abnormalities among the cases with genomic changes were gains on chromosome regions 1q (45%), 5q (24%), 9q (24%), 11q (22%), 15q (22%), 3q (16%), and 7q (14%), while losses mainly involved chromosomes 13 (39%), 16q (18%), 6q (10%), and 8p (10%). Remarkably, the 6 patients with gains on 11q had IGH translocations. Multivariate analysis selected chromosomal losses, 11q gains, age, and type of treatment (conventional chemotherapy vs autologous transplantation) as independent parameters for predicting survival. Genomic losses retained the prognostic value irrespective of treatment approach. According to these results, losses of chromosomal material evaluated by CGH represent a powerful prognostic factor in MM patients.     

Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena

Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disorder for which the best therapeutic option is not yet well established. Immune-related disorders are rare complications of MCD. We report on an MCD case in a 23-year-old patient with extensive abdominal involvement and associated immune hemolytic anemia and Raynaud phenomenon. He was negative for human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8). After 8 courses of the anti-CD20 monoclonal antibody (rituximab), the patient achieved complete remission. Interestingly, Raynaud phenomenon disappeared under treatment and no new hemolytic events occurred. Anti-CD20 antibody treatment could be an attractive therapeutic approach for MCD, mainly when immune-related disorders are associated.     

Interleukin-2 and natural killer activity in acute type B hepatitis

Natural killer (NK) cell activity against K562 cell line, and interleukin-2 (IL-2) activity in supernatants from lectin-activated PBMC cultures from 17 patients with acute hepatitis B in the early phase of illness were studied. These patients showed enhanced NK cytotoxicity and higher levels of IL2 activity as compared with control subjects. There was a positive correlation between cytotoxicity values and levels of IL2 activity. Furthermore, in the recovery phase of illness there was a tendency towards normalization in both parameters. When patients were divided in accordance with markers of HBV replication, HBV-DNA positive patients showed increased NK cell activity and IL2 levels as compared with the control group, whereas in HBV-DNA-negative patients no differences were found. However, no differences were found between patients with HBeAg and patients with anti-HBe. These results suggest that natural cytotoxicity is increased early in the course of acute hepatitis B, while NK cell activity returns to normal later, during convalescence. Enhanced NK cell activity appears to be secondary, at least in part, to increased production of IL2. Natural cytotoxicity may be one mechanism that controls the HBV infection before other cytotoxic mechanisms become fully operative.     

Urinary tract infection due to Corynebacterium urealyticum in kidney transplant recipients: an underdiagnosed etiology for obstructive uropathy and graft dysfunction-results of a prospective cohort study.

BACKGROUND: Corynebacterium urealyticum is a cause of urinary tract infection and encrusting cystitis or pyelitis. Information about this infection in renal transplant recipients is based on case reports. We communicate the first prospective epidemiological study for this population. METHODS: We selected a cohort of 163 renal transplant recipients who were screened for urinary tract infection due to C. urealyticum. Long-term incubation and special media were used for culture of C. urealyticum. The cohort was observed for a mean of 26.2 months (standard deviation, 8.7; range, 1-36 months). Risk factors and outcomes were assessed. RESULTS: At baseline, 16 (9.8%) of 163 patients had C. urealyticum bacteriuria (6 were asymptomatic, 9 had acute cystitis, and 1 had encrusting pyelitis). Independent risk factors (assessed by multivariate analysis) for urinary tract C. urealyticum infection were: antibiotic administration during the previous month (odds ratio, 8.04; 95% confidence interval, 1.57-41.06; P = .012), history of nephrostomy (odds ratio, 51.59; 95% confidence interval, 3.62-736.06; P = .004), and skin colonization (odds ratio, 208.35; 95% confidence interval, 21.54-2015.22; P< .001). Presence of urinary tract infection symptoms for >1 month (odds ratio, 27.7; 95% confidence interval, 2.55-300.5; P = .006) and obstructive uropathy (odds ratio 25.9; 95% confidence interval, 4.43-152.31; P < .001) were more frequent during follow-up in patients with C. urealyticum bacteriuria. CONCLUSIONS: When specifically tested for, C. urealyticum bacteriuria is more prevalent than previously thought in renal transplant recipients, and it is closely related to obstructive uropathy. Future studies are necessary to establish the relevance of treating the infection during follow-up after renal transplantation.     

Multidisciplinary protocol of preoperative and surgical management of patients with pituitary tumors candidates to pituitary surgery

The optimal planning of preoperative diagnosis, management and treatment of pituitary tumors (PT) candidates to pituitary surgery (PS) requires a multidisciplinary approach involving a team of endocrinologists, neurosurgeons, ENT, neuro-ophthalmologists and neuroradiologists with experience in pituitary diseases. Such teams improve surgical results, minimize complications and facilitate their correct treatment if occurring, and optimize the hormonal, ophthalmological and radiological preoperative and follow-up evaluation. We have developed a clinical practice protocol for patients with PT who are candidates to PS based on the most recent national and international guidelines and the relevant literature regarding PT published in the last years. The protocol has been elaborated by a multidisciplinary team of a Spanish Pituitary Tumor Center of Excellence (PTCE) that includes at least one neurosurgeon, ENT, neuroradiologist, neuro-ophthalmologist, endocrine pathologist and endocrinologist specialized in pituitary diseases. We elaborated this guideline with the aim of sharing our experience with other centers involved in the perioperative and surgical management of PT thereby facilitating the management of patients undergoing PS.