Targetable genetic features of primary testicular and primary central nervous system lymphomas.

Primary central nervous system lymphomas (PCNSLs) and primary testicular lymphomas (PTLs) are extranodal large B-cell lymphomas (LBCLs) with inferior responses to current empiric treatment regimens. To identify targetable genetic features of PCNSL and PTL, we characterized their recurrent somatic mutations, chromosomal rearrangements, copy number alterations (CNAs), and associated driver genes, and compared these comprehensive genetic signatures to those of diffuse LBCL and primary mediastinal large B-cell lymphoma (PMBL). These studies identify unique combinations of genetic alterations in discrete LBCL subtypes and subtype-selective bases for targeted therapy. PCNSLs and PTLs frequently exhibit genomic instability, and near-uniform, often biallelic, CDKN2A loss with rare TP53 mutations. PCNSLs and PTLs also use multiple genetic mechanisms to target key genes and pathways and exhibit near-uniform oncogenic Toll-like receptor signaling as a result of MYD88 mutation and/or NFKBIZ amplification, frequent concurrent B-cell receptor pathway activation, and deregulation of BCL6. Of great interest, PCNSLs and PTLs also have frequent 9p24.1/PD-L1/PD-L2 CNAs and additional translocations of these loci, structural bases of immune evasion that are shared with PMBL.

A Clinical Prediction Model to Assess Risk for Chemotherapy-Related Hospitalization in Patients Initiating Palliative Chemotherapy.

IMPORTANCE: Chemotherapy-related hospitalizations in patients with advanced cancer are common, distressing, and costly. Methods to identify patients at high risk of chemotherapy toxic effects will permit development of targeted strategies to prevent chemotherapy-related hospitalizations. OBJECTIVE: To demonstrate the feasibility of using readily available clinical data to assess patient-specific risk of chemotherapy-related hospitalization. DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study conducted from January 2003 through December 2011 at the Mass General/North Shore Cancer Center, a community-based cancer center in northeastern Massachusetts. The parent cohort included 1579 consecutive patients with advanced solid-tumor cancer receiving palliative-intent chemotherapy. Case patients (n = 146) included all patients from the parent cohort who experienced a chemotherapy-related hospitalization. Controls (n = 292) were randomly selected from 1433 patients who did not experience a chemotherapy-related hospitalization. EXPOSURES: Putative risk factors for chemotherapy-related hospitalization-including patient characteristics, treatment characteristics, and pretreatment laboratory values-were abstracted from medical records. Multivariable logistic regression was used to model the patient-specific risk of chemotherapy-related hospitalization. MAIN OUTCOMES AND MEASURES: Chemotherapy-related hospitalization, as adjudicated by the oncology clinical care team within a systematic quality-assessment program. RESULTS: A total of 146 (9.2%) of 1579 patients from the parent cohort experienced a chemotherapy-related hospitalization. In multivariate regression, 7 variables were significantly associated with chemotherapy-related hospitalization: age, Charlson comorbidity score, creatinine clearance, calcium level, below-normal white blood cell and/or platelet count, polychemotherapy (vs monotherapy), and receipt of camptothecin chemotherapy. The median predicted risk of chemotherapy-related hospitalization was 6.0% (interquartile range [IQR], 3.6%-11.4%) in control patients and 14.7% (IQR, 6.8%-22.5%) in case patients. The bootstrap-adjusted C statistic was 0.71 (95% CI, 0.66-0.75). At a risk threshold of 15%, the model exhibited a sensitivity of 49% (95% CI, 41%-57%) and a specificity of 85% (95% CI, 81%-89%) for predicting chemotherapy-related hospitalization. CONCLUSIONS AND RELEVANCE: In patients initiating palliative chemotherapy for cancer, readily available clinical data were associated with the patient-specific risk of chemotherapy-related hospitalization. External validation and evaluation in the context of a clinical decision support tool are warranted.

Mastering cardiac murmurs: the power of repetition.

BACKGROUND: The ability of medical students to recognize heart murmurs is poor (20%), and does not improve with subsequent years of training. A teaching method to improve this skill would be useful. STUDY OBJECTIVES: To determine whether intensive repetition of four basic cardiac murmurs improves auscultatory proficiency in medical students. DESIGN: Controlled intervention study. SUBJECTS: Fifty-one second-year medical students in an east coast medical school. INTERVENTIONS: Subjects were classified into three groups: (1) a monitored group, who listened to 500 repetitions of each murmur in a monitored setting, (2) an unmonitored group, who listened to 500 repetitions of each murmur in an unmonitored setting, and (3) a control group. All three groups were tested using a pretest and posttest methodology. MEASUREMENTS AND RESULTS: The 20 subjects in the monitored group improved from 13.5 +/- 9.8 to 85 +/- 17.6% following the intervention (mean +/- SD). Similarly, 21 students in the unmonitored group improved from 20.9 +/- 10.9 to 86.1 +/- 15.6%. Ten control students showed no significant improvement (24 +/- 21.7 to 32 +/- 22.5%). The differences between the two intervention groups and the control subjects was significant at p < 0.001 by analysis of variance. CONCLUSION: Five hundred repetitions of four basic cardiac murmurs significantly improved auscultatory proficiency in recognizing basic cardiac murmurs by medical students. These results suggest that cardiac auscultation is, in part, a technical skill.

HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature.

Primary effusion lymphoma (PEL) is a rare extranodal lymphoma that typically presents in a body cavity in the absence of a detectable tumor mass and that occurs predominantly in immunosuppressed individuals. The neoplastic lymphoid cells are frequently infected with human herpes virus 8 (HHV8), also known as Kaposi sarcoma herpes virus (KSHV). We describe two HIV-negative patients who presented with primary effusion lymphoma of B-cell lineage involving the pleural cavity, but whose tumor cells lacked infection by HHV8. We review the English language literature of HHV8-negative PEL of B-cell lineage and compare these lymphomas to HHV8-associated PEL with regard to clinical and pathological characteristics, therapy, and outcome.