Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). The International Myeloma Working Group (IMWG) developed guidelines recommending primary thromboprophylaxis, in those identified at high‐risk of VTE by the presence of risk factors. The National Comprehensive Cancer Network (NCCN) has adopted these guidelines; however, they lack validation. We sought to develop and validate a risk prediction score for VTE in MM and to evaluate the performance of the current IMWG/NCCN guidelines. Using 4446 patients within the Veterans Administration Central Cancer Registry, we used time‐to‐event analyses to develop a risk score for VTE in patients with newly diagnosed MM starting chemotherapy. We externally validated the score using the Surveillance, Epidemiology, End Results (SEER)‐Medicare database (N = 4256). After identifying independent predictors of VTE, we combined the variables to develop the IMPEDE VTE score (Immunomodulatory agent; Body Mass Index ≥25 kg/m2; Pelvic, hip or femur fracture; Erythropoietin stimulating agent; Dexamethasone/Doxorubicin; Asian Ethnicity/Race; VTE history; Tunneled line/central venous catheter; Existing thromboprophylaxis). The score showed satisfactory discrimination in the derivation cohort, c‐statistic = 0.66. Risk of VTE significantly increased as score increased (hazard ratio 1.20, P = <.0001). Within the external validation cohort, IMPEDE VTE had a c‐statistic of 0.64. For comparison, when evaluating the performance of the IMWG/NCCN guidelines, the c‐statistic was 0.55. In summary, the IMPEDE VTE score outperformed the current IMWG/NCCN guidelines and could be considered as the new standard risk stratification for VTE in MM.

Cancer-testis antigens (CTAs) represent potential targets for cancer immunotherapy because these proteins are widely distributed in tumors but not in normal tissues, except testes. In this paper, we identify homology of the CTA CTp11 with SPAN-X (sperm protein associated with the nucleus mapped to the X chromosome). On two-dimensional Western blots of human sperm extracts, SPAN-X antibodies recognized 19 spots ranging from 20 to 23 kDa with isoelectric points from 5.0 to 5.5. Differential extraction of spermatozoa demonstrated that the SPAN-X protein is highly insoluble. Only 50% of ejaculated spermatozoa exhibited SPAN-X immunofluorescent staining. Dual localization of the sex chromosomes and the SPAN-X protein demonstrated that an equal number of X- and Y-bearing spermatozoa exhibited SPAN-X staining. In transfected mammalian CV1 cells, the SPAN-Xa and SPAN-Xb proteins were localized to the nucleus and cytoplasm, respectively, by indirect immunofluorescence. On immunoblots of CV1 cells, the SPAN-Xa protein migrated at 15-20 kDa, whereas the SPAN-Xb protein migrated at a higher molecular weight of 21-22 kDa. The SPAN-X protein was ultrastructurally associated with nuclear vacuoles and the redundant nuclear envelope. SPAN-X is the first protein specifically localized to these poorly characterized structures of the mammalian sperm nucleus and provides a unique biochemical marker for investigation of their function in spermatozoa as well as the role of SPAN-X/CTp11 in human tumors.

Background Multiple myeloma (MM) is one of the most common hematologic malignancies in the United States and is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Methods A retrospective cohort of patients in the U.S. Veterans Health Administration database diagnosed with MGUS between 1, October, 1999 and 31, December, 2009 and diabetes mellitus prior to their MGUS diagnosis was identified and followed through 6, August, 2013. Patient-level clinical data were reviewed to verify diagnoses and to abstract data on size of baseline M-protein and type of MGUS, i.e., immunoglobulin (Ig) subtype or light-chain, when available. Metformin users were defined as patients that were prescribed metformin for at least 4 years, with no single break between consecutive prescriptions ≥6 months. Kaplan-Meier curves and Cox models were used to analyze the association between metformin use and the progression of MGUS to MM. Findings The analytic cohort consisted of 2,003 MGUS patients with a median follow-up time of 69 months. Within the analytic cohort, 463 metformin users (23·1%) were identified. Among the metformin users, 13 patients progressed to MM, while 74 patients progressed to MM among the non-metformin users. Metformin use was associated with a reduced risk of transformation to MM (Hazard ratio, HR: 0·47; 95% confidence interval, CI: 0·25–0·87). Interpretation For diabetics diagnosed with MGUS, metformin use for 4 years or longer was associated with a reduced risk of transformation of MGUS to MM. Prospective studies are required to determine whether this association is causal and whether these results can be extrapolated to non-diabetics.

Obesity and black race are risk factors for transformation of MGUS to MM. Future clinical trials should examine whether weight loss is a way to prevent the progression to MM in MGUS patients.

The optimal treatment strategy for cT2N0 esophageal cancer depends on the accuracy of endoscopic ultrasound staging. High-risk features that confer increased probability of upstaging can inform clinical decision making to recommend induction chemoradiation for select cT2N0 patients.