Effect of off-pump coronary artery bypass grafting on risk-adjusted and cumulative sum failure outcomes after coronary artery surgery

BACKGROUND AND AIM: We have shown that cumulative sum (CUSUM) failure analysis may be more sensitive than standard statistical methods in detecting a cluster of adverse patient outcomes after cardiac surgical procedures. We therefore applied CUSUM, as well as standard statistical techniques, to analyze a surgeon's experience with off-pump coronary artery bypass grafting (OPCAB) and on-pump procedures to determine whether the two techniques have similar or different outcomes. METHODS: In 320 patients undergoing nonemergent, first time coronary artery bypass grafting, preoperative patient characteristics, rates of mortality and major complications, and ICU and hospital lengths of stay were compared between the on-pump and OPCAB cohorts using Fisher's exact tests and Wilcoxon two sample tests. Predicted mortality and length of stay were determined using previously validated models of the Cardiac Care Network of Ontario. Observed versus expected ratios of both variables were calculated for the two types of procedures. Furthermore, CUSUM curves were constructed for the on-pump and OPCAB cohorts. A multivariable analysis of the predictors of hospital length of stay was also performed to determine whether the type of coronary artery bypass procedure had an independent impact on this variable. RESULTS: The predicted mortality risk and predicted hospital length of stay were almost identical in the 208 on-pump patients (2.2 +/- 3.9%; 8.2 +/- 2.5 days) and the 112 OPCAB patients (2.0 +/- 2.2%; 7.8 +/- 2.1 days). The incidence of hospital mortality and postoperative stroke were 2.9% and 2.4% in on-pump patients versus zero in OPCAB patients (p = 0.09 and 0.17, respectively). Mechanical ventilation for greater than 48 hours was significantly less common in OPCAB (1.8%) than in on-pump patients (7.7%, p = 0.04). The rate of 10 major complications was 14.9% in on-pump versus 8.0% in OPCAB patients (p = 0.08). OPCAB patients experienced a hospital length of stay that was a median of 1.0 day shorter than on-pump patients (p = 0.01). The observed versus expected ratio for length of stay was 0.78 in OPCAB patients versus 0.95 in on-pump patients. On CUSUM analysis, the failure curve in OPCAB patients was negative and was flatter than that of on-pump patients throughout the duration of the study. Furthermore, OPCAB was an independent predictor of a reduced hospital length of stay on multivariable analysis. CONCLUSIONS: OPCAB was associated with better outcomes than on-pump coronary artery bypass despite a similar predicted risk. This robust finding was documented on sensitive CUSUM analysis, using standard statistical techniques and on a multivariable analysis of the independent predictors of hospital length of stay.     

Intestinal transplantation: laboratory experience and report of a clinical case

The experimental intestinal transplantation in our laboratory and elsewhere is briefly reviewed. Replantation of the entire jejunoileum is compatible with long-term survival of experimental animals. Lymphatic pathways severed during the procedure fully regenerated within a few weeks. Contrary to the implication of earlier studies on this subject, it is now believed that intestinal allografts are rejected in the same manner as other organs, and the rejection response is definitely mitigated by immunosuppressive drugs. There is no conclusive evidence of a graft versus host reaction despite the fact that transplantation of the entire jejunoileum represents a large antigenic mass and transplantation of many mesenteric lymph nodes. The time necessary for regeneration of lymphatic pathways after allotransplantation is different from that after replantation.     

The lymphomas: molecular pathways and novel therapeutic targets

In recent years, several molecular mechanisms involved in promoting cancer cell survival and growth have been identified. These discoveries helped in designing and testing novel drugs that target specific cellular pathways. In this review, we focus on new molecular targets that are currently being explored for the treatment of non-Hodgkin's lymphoma and Hodgkin's lymphoma.     

Ethical issues in non-heart-beating donation

A shortage of organ donors and the large number of patients desperately waiting for kidney transplant have led to the search for new sources of transplantable organs. The waiting list has grown at an alarming rate resulting in increased waiting times and deaths. The introduction of non heart beating (NHB) donation programmes generates a lot of ethical issues. How should death of a patient be defined in the case of NHB donation? Is there a strict separation of responsibilities of the medical teams in the different phases of the procedure (patient treatment and actual donation)? How should consent be obtained? Is sufficient respect and care given to the patient and his family? How is the viability of the organs assessed and how should the organs be allocated? We believe that it is very important to debate these issues and to try to outline an ethical framework for NHB donation that can enjoy the widest possible community support.     

The Edpm5 locus prevents the 'angiogenic switch' in an estrogen-induced rat pituitary tumor

Edpm5 is one member of a group of quantitative trait loci that are responsible for the difference in susceptibility to estrogen-induced prolactinoma between the Fischer 344 (F344) and Brown Norway (BN) strains. Upon chronic estrogen treatment F344 rats develop large, hemorrhagic and invasive pituitary tumors, which exhibit both tumor angiogenesis and neoplasia. In contrast, BN rats do not develop a tumor despite an estrogen-induced increase in lactotroph density. To investigate the role of Edpm5 in the development of these tumors, we have generated a novel congenic rat strain F344.BN-Edpm5BN by introgressing the segment of rat chromosome bearing Edpm5 from BN into the F344 strain background. Phenotypic differences between F344 and F344.BN-Edpm5BN must be due to a gene(s) within the chromosomal interval encompassing Edpm5. Through use of these strains, we find that Edpm5 specifically regulates the switch to angiogenic phenotype, independent of neoplasia. The F344.BN-Edpm5BN rats developed tumors, which exhibited significant growth, 7-fold greater mass than the pituitary of untreated rats, and neoplasia indistinguishable from that of the F344 strain. However, the F344.BN-Edpm5BN rat tumor had a non-angiogenic phenotype. After chronic estrogen treatment, there was no increase in microvessel count over untreated controls in F344.BN-Edpm5BN tumors, whereas F344 rat tumors showed a significant increase (P < 0.0005). The ultrastructural morphology of the pituitary blood vessels also did not show significant angiogenesis associated changes in F344.BN-Edpm5BN rat pituitary tumors. In contrast the parental strain F344 had pronounced angiogenic activity. The F344.BN-Edpm5BN strain also fails to express VEGF at the high levels seen in the F344 rat pituitary after estrogen treatment. Hence at least one gene that has a large impact, directly or indirectly, on the switch to angiogenic phenotype must reside within the chromosomal interval that is the Edpm5 quantitative trait locus.     

Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma

BACKGROUND: The reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15-30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown. METHODS: From March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow-up evaluations. RESULTS: Only 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients. CONCLUSIONS: Gastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study.     

A pilot study of rituximab in patients with recurrent,classic Hodgkin disease

BACKGROUND: To explore the potential role of infiltrating benign B cells in classic Hodgkin disease (HD) lesions in supporting the survival of malignant Hodgkin and Reed-Sternberg (H/RS) cells, the authors initiated a pilot study of rituximab. Rituximab is used to primarily deplete normal B cells from HD lesions. METHODS: Patients with recurrent, classic HD who had received a minimum of two prior treatment regimens, regardless of whether H/RS cells expressed CD20, were treated with 6 weekly doses of 375 mg/m2 rituximab to selectively deplete infiltrating benign B cells. Objective tumor response was determined 3 weeks after completion of the last dose of rituximab and every 3 months thereafter. Serum samples were collected from patients before they started rituximab therapy and 3 weeks after the final course of rituximab. Serum cytokine levels of interleukin 6 (IL-6), IL-10, IL-12, IL-13, and interferon gamma were determined using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Twenty-two patients with nodular sclerosis histology were evaluable for treatment response. Five patients (22%) achieved partial or complete remission that lasted for a median of 7.8 months (range, 3.3-14.9 months). Remissions were observed in patients only at lymph node and splenic sites, but not at extranodal sites, and were irrespective of CD20 expression by H/RS cells. Furthermore, systemic (B) symptoms resolved in six of seven patients after therapy. In two patients, partial remissions were associated with a decline in serum IL-6 levels. CONCLUSIONS: The current data suggest that rituximab therapy in patients with recurrent, classic HD can alter serum IL-6 cytokine levels, can improve B symptoms, and may result in clinical remissions.     

Elevation of brain natriuretic peptide levels in children with septic shock

OBJECTIVES: 1) To compare brain natriuretic peptide levels in pediatric patients with septic shock with both children admitted to the pediatric intensive care unit without infection and with healthy subjects; and 2) to evaluate the correlation between brain natriuretic peptide with severity of illness and with myocardial dysfunction in children with septic shock. DESIGN:: Prospective, observational study. SETTING: Children's Hospital pediatric intensive care unit. PATIENTS: Children from age 2 wks to 18 yrs. Thirteen children with septic shock requiring inotropic support, 12 healthy controls, and five critically ill patients without infection or heart disease were evaluated. INTERVENTIONS: For patients with septic shock, brain natriuretic peptide was measured within 6 hrs of admission and throughout the pediatric intensive care unit course. Echocardiograms were performed within 12 hrs of admission and then repeated if the patient continued to require inotropic support. For controls, one measurement was performed. MEASUREMENTS AND MAIN RESULTS: Children with septic shock had an elevated (p < 0.0001) brain natriuretic peptide on admission (median 115 pg/mL [range 26-2960]) when compared with healthy (9 pg/mL [5-30]) and pediatric intensive care unit controls (10 pg/mL [5-30]). In patients with septic shock, brain natriuretic peptide at 12 hrs correlated directly with Pediatric Risk of Mortality III score (rs = .80, p = 0.002) and inversely with fractional shortening (rs = -.66, p = 0.014). In children with cold shock, brain natriuretic peptide at 12 hrs (718 pg/mL) [63-1530] was higher (p = 0.007) than in those with warm shock (208 pg/mL [20-366]). There was no pattern (p > 0.05) observed for brain natriuretic peptide over time. CONCLUSIONS: Brain natriuretic peptide measured early after admission is increased in children with septic shock, especially in those with cold shock. In addition, the level at 12 hrs correlates with both severity of illness and myocardial dysfunction. Brain natriuretic peptide may be useful in assessing myocardial dysfunction from septic shock, particularly in identifying children with cold shock. Further studies are warranted to determine whether this measurement will be helpful in guiding therapy in pediatric septic shock.     

Quality of survival in histiocytosis X: A southwest oncology group study

Sixty children survived for five years after the diagnosis of histiocytosis X. Serious disabilities were seen in 50% of children whose disease involved soft tissue and bone. Late deaths from pulmonary failure were associated with opportunistic infections in two cases. Future treatment approaches must weigh the risks of therapy-related complications against the probability of significant disability if the disease continues for many years.