Delivering Challenging News: An Illness-Trajectory Communication Curriculum for Multispecialty Oncology Residents and Fellows

Introduction: Published curricula to teach communication skills for postgraduate fellows in oncology are few in number despite the fact that oncologists conduct many difficult discussions with their patients and their families. Such discussions may include disclosing initial diagnosis or relapse of a patient\u27s cancer or relaying a poor prognosis or change to palliative care. Methods: An eight-module course on communication in oncology practice was delivered over 2 months for palliative and oncology fellows and radiation oncology residents. Learners were given a precourse survey in which they were asked to rate their proficiency in various communication tasks. Each learner then participated in a videotaped precourse objective structured clinical exam (OSCE) on breaking bad news with standardized patients (SPs). The course took place over 8 weeks with weekly didactics and role-play. At the end of the course, a second OSCE took place. After the course was completed, the fellows again filled out a proficiency survey. Results: Twenty-two learners participated over 2 years of this course. Participants reported a significant increase in perceived competence in all areas on the postcourse survey. SP feedback on OSCEs pre- and postcourse indicated improvement in skills for learners. Pre- and postcourse OSCE video assessment revealed a significant improvement in global communication skills. Discussion: Initial data show that this course successfully improved communication skills and increased fellows\u27 comfort level across several domains of communication. Future directions include validating our assessment tool, expanding the topic base, and investigating the impact on practice after course completion

Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases

Background: Complement C2 deficiency is the most common genetically determined complete complement deficiency and is associated with a number of diseases. Most prominent are the associations with recurrent serious infections in young children and the development of systemic lupus erythematosus (SLE) in adults. The links with these diseases reflect the important role complement C2 plays in both innate immunity and immune tolerance. Infusions with normal fresh frozen plasma for the treatment of associated disease have demonstrated therapeutic effects but so far protein replacement therapy has not been evaluated. Results: Human complement C2 was cloned and expressed in a mammalian cell line. The purity of recombinant human C2 (rhC2) was greater than 95% and it was characterized for stability and activity. It was sensitive to C1s cleavage and restored classical complement pathway activity in C2-deficient serum both in a complement activation ELISA and a hemolytic assay. Furthermore, rhC2 could increase C3 fragment deposition on the human pathogen Streptococcus pneumoniae in C2-deficient serum to levels equal to those with normal serum. Conclusions: Taken together these data suggest that recombinant human C2 can restore classical complement pathway activity and may serve as a potential therapeutic for recurring bacterial infections or SLE in C2-deficient patients

Hereditary Vascular Retinopathy, Cerebroretinal Vasculopathy, and Hereditary Endotheliopathy with Retinopathy, Nephropathy, and Stroke Map to a Single Locus on Chromosome 3p21.1-p21.3

We performed a genomewide search for linkage in an extended Dutch family with hereditary vascular retinopathy associated with migraine and Raynaud phenomenon. Patients with vascular retinopathy are characterized by microangiopathy of the retina, accompanied by microaneurysms and telangiectatic capillaries. The genome search, using a high throughput capillary sequencer, revealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum pairwise LOD score 5.25, with D3S1578). Testing of two additional families that had a similar phenotype, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage to the same chromosomal region (combined maximum LOD score 6.30, with D3S1588). Haplotype analysis of all three families defined a 3-cM candidate region between D3S1578 and D3S3564. Our study shows that three autosomal dominant vasculopathy syndromes with prominent cerebroretinal manifestations map to the same 3-cM interval on 3p21, suggesting a common locus

Thrombomodulin mutations in atypical hemolyticuremic syndrome

BACKGROUND: The hemolytic–uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. The common form of the syndrome is triggered by infection with Shiga toxin–producing bacteria and has a favorable outcome. The less common form of the syndrome, called atypical hemolytic–uremic syndrome, accounts for about 10% of cases, and patients with this form of the syndrome have a poor prognosis. Approximately half of the patients with atypical hemolytic–uremic syndrome have mutations in genes that regulate the complement system. Genetic factors in the remaining cases are unknown. We studied the role of thrombomodulin, an endothelial glycoprotein with anticoagulant, antiinflammatory, and cytoprotective properties, in atypical hemolytic–uremic syndrome. METHODS: We sequenced the entire thrombomodulin gene (THBD) in 152 patients with atypical hemolytic–uremic syndrome and in 380 controls. Using purified proteins and cell-expression systems, we investigated whether thrombomodulin regulates the complement system, and we characterized the mechanisms. We evaluated the effects of thrombomodulin missense mutations associated with atypical hemolytic–uremic syndrome on complement activation by expressing thrombomodulin variants in cultured cells. RESULTS: Of 152 patients with atypical hemolytic–uremic syndrome, 7 unrelated patients had six different heterozygous missense THBD mutations. In vitro, thrombomodulin binds to C3b and factor H (CFH) and negatively regulates complement by accelerating factor I–mediated inactivation of C3b in the presence of cofactors, CFH or C4b binding protein. By promoting activation of the plasma procarboxypeptidase B, thrombomodulin also accelerates the inactivation of anaphylatoxins C3a and C5a. Cultured cells expressing thrombomodulin variants associated with atypical hemolytic–uremic syndrome had diminished capacity to inactivate C3b and to activate procarboxypeptidase B and were thus less protected from activated complement. CONCLUSIONS: Mutations that impair the function of thrombomodulin occur in about 5% of patients with atypical hemolytic–uremic syndrome