Mutational analysis of IgVH and BCL-6 genes suggests thymic B-cells origin of mediastinal (thymic) B-cell lymphoma.

Mediastinal (thymic) large B-cell lymphoma (MBL) has been defined as a subtype of diffuse large B-cell lymphoma (DLBL) arising in the mediastinum with characteristic clinicopathological features. It has been postulated that MBL arise from non-circulating thymic B-cells and represent a distinct lymphoma entity, however, the histogenesis of the disease is not yet fully understood. In order to clarify the histogenetic derivation of MBL and to determine the relationship of MBL to thymic B-cells we have analyzed the nucleic acid sequences of immunoglobulin (Ig) heavy chain variable region (VH) and 5' noncoding region of BCL-6 genes in normal thymic B-cells and six cases of MBL. Thymic B-cells and tumor cells of MBLs displayed hypermutated VH and/or BCL-6 genes but intraclonal divergence did not associate with these mutations. Since somatic mutations of the IgVH and BCL-6 genes are histogenetic markers of B-cell transit through the germinal centre (GC), these results suggest that both thymic B-cells and MBLs derived from GC or an equivalent environment where B-cells underwent somatic hypermutation. The similar pattern of mutations of IgVH and BCL-6 genes found in thymic B-cells and MBLs further supports the theory that MBLs originate from thymic B-cells.

Errors and the burden of errors: attitudes, perceptions, and the culture of safety in pediatric cardiac surgical teams.

BACKGROUND: The fear of committing clinical errors in perioperative care has a negative impact on the psychological well-being of surgical team members and ultimately on patient care. We assessed the perceptions and attitudes of surgical teams relative to committing errors, the impact of errors, and the culture of safety. METHODS: Pediatric cardiac surgery team members at three academic hospitals were surveyed. The survey included scaled, open-ended questions and a clinical vignette. Respondents were asked about the safety climate, team climate, stress recognition, and the impact of error as they relate to making and the anticipation of making clinical errors. RESULTS: The response rate was 69%. Safety attitudes were influenced by the work environment climate. Many respondents felt unable to express disagreement and had difficulty raising safety concerns. Staffing levels, equipment availability, production pressures, and hectic schedules were concerns. Respondents admitted that errors occurred repeatedly, and that guidelines and policies were often disregarded. CONCLUSIONS: A psychometrically sound teamwork culture tool was used and demonstrated that surgical teams are influenced by the recognition of medical errors and that these errors carry significant personal burden. The findings suggest that the safety attitudes among team members may impact their performance and need to be carefully taken into consideration. Providers' reluctance to share safety events with others, as well as the perceived powerlessness to prevent events, must be addressed as part of an overall strategy to improve patient care outcomes. The study points to the need to address teamwork culture in efforts to improve patient care.

A prospective observational study of human factors, adverse events, and patient outcomes in surgery for pediatric cardiac disease.

OBJECTIVE: To explore the impact of human factors on intraoperative adverse events and compensation mechanisms in pediatric cardiac surgery. METHODS: Prospective observations of pediatric cardiac surgical procedures were conducted. Patient complexity scores were calculated and outcomes recorded. The process of care was divided into epochs. Events were extracted and coded into compensated or uncompensated major and minor adverse events. Linear regression and analysis of variance were used to analyze the relationships between epochs, complexity, adverse events, and outcome. Patient-specific and procedure-specific variables were tested in a forward stepwise logistic regression as predictors of cases with 1 or more major adverse events. RESULTS: One hundred two patients undergoing pediatric cardiac surgery were observed. An average of 1.2 (range 0-6) major adverse events occurred per case. The most common type of major adverse event was cardiovascular, and most occurred during the surgery/postbypass epoch. Cognitive compensation was the most common compensation mechanism for major adverse events. An average of 15.3 minor adverse events occurred per case. Minor adverse events occurred frequently during the surgery/bypass epoch and related to communication and coordination failures. Higher case complexity, longer surgery duration, and higher number of major adverse events per patient correlated with death compared with other outcome groups (P < .01). Case complexity (P < .01) and surgery duration (P < .05) were both significant predictors of major adverse events. CONCLUSIONS: Pediatric cardiac surgery is an ideal model to study the coordinated efforts of team members in a complex organizational structure. Adverse events occurred routinely during pediatric cardiac surgery and were mostly compensated. Case complexity was a significant predictor of major adverse events. The number of major adverse events per patient correlated with clinical outcomes.

Aberrant somatic hypermutation and expression of activation-induced cytidine deaminase mRNA in mediastinal large B-cell lymphoma.

To determine the possible role of aberrant somatic hypermutation (ASHM) and activation-induced cytidine deaminase (AID) expression in the pathogenesis of mediastinal large B-cell lymphoma (MBL), the mutational status of genes affected by ASHM, including c-MYC, PAX-5 and RhoH, was analysed, and the expression level of AID mRNA in tumour specimens from six patients with MBL was determined. Mutations in one or more genes and high expression of AID mRNA were detected in all the six cases of MBL. These results suggest that ASHM and AID expression may have a role in the pathogenesis of MBL.