Heterologous Tissue Culture Expression Signature Predicts Human Breast Cancer Prognosis

BACKGROUND: Cancer patients have highly variable clinical outcomes owing to many factors, among which are genes that determine the likelihood of invasion and metastasis. This predisposition can be reflected in the gene expression pattern of the primary tumor, which may predict outcomes and guide the choice of treatment better than other clinical predictors. METHODOLOGY/PRINCIPAL FINDINGS: We developed an mRNA expression-based model that can predict prognosis/outcomes of human breast cancer patients regardless of microarray platform and patient group. Our model was developed using genes differentially expressed in mouse plasma cell tumors growing in vivo versus those growing in vitro. The prediction system was validated using published data from three cohorts of patients for whom microarray and clinical data had been compiled. The model stratified patients into four independent survival groups (BEST, GOOD, BAD, and WORST: log-rank test p = 1.7×10(−8)). CONCLUSIONS: Our model significantly improved the survival prediction over other expression-based models and permitted recognition of patients with different prognoses within the estrogen receptor-positive group and within a single pathological tumor class. Basing our predictor on a dataset that originated in a different species and a different cell type may have rendered it less sensitive to proliferation differences and endowed it with wide applicability. SIGNIFICANCE: Prognosis prediction for patients with breast cancer is currently based on histopathological typing and estrogen receptor positivity. Yet both assays define groups that are heterogeneous in survival. Gene expression profiling allows subdivision of these groups and recognition of patients whose tumors are very unlikely to be lethal and those with much grimmer outlooks, which can augment the predictive power of conventional tumor analysis and aid the clinician in choosing relaxed vs. aggressive therapy

Synergistic effect of acute renal failure and respiratory failure in the surgical intensive care unit.

A retrospective evaluation of the effect of renal and respiratory failure on mortality in our surgical intensive care unit was undertaken. The coexistence of combined renal and respiratory failure had a synergistic adverse effect on survival. Combined pulmonary and kidney failure appeared to develop simultaneously. A subset of patients with severe prerenal azotemia but without uremia had the highest mortality. These results are not consistent with the simple combination of single systems failure but rather suggest that renal and respiratory failure are makers of a generalized underlying defect

Syndrome of inappropriate antidiuresis in Waldenström\u27s macroglobulinemia.

Hyponatremia due to the syndrome of inappropriate antidiuresis rather than due to isotonic hyponatremia from hyperproteinemia developed in a patient with Waldenström\u27s macroglobulinemia. The patient was unable to excrete a water load normally despite suppression of antidiuretic hormone to normal levels. The temporal relationship between control of the tumor and resolution of the hyponatremia suggests that the tumor either produced a substance that enhanced the hydro-osmotic effect of endogenous antidiuretic hormone or produced an antidiuretic substance immunologically different from antidiuretic hormone. The syndrome of inappropriate antidiuresis should be suspected in hyponatremic patients with Waldenström\u27s macroglobulinemia

Renal angiomyolipoma with arteriovenous shunting.

We describe a patient with arteriovenous shunting during renal arteriography who at operation was found to have an angiomyolipoma rather than renal cell carcinoma or an arteriovenous malformation. Renal angiomyolipoma should be added to the list of causes of gross hematuria with angiographically demonstrable arteriovenous shunting

Evidence for Ambient-Temperature Reversible Catalytic Hydrogenation in Pt-Doped Carbons

In situ high-pressure Raman spectroscopy, with corroborating density functional calculations, is used to probe C-H chemical bonds formed when dissociated hydrogen diffuses from a platinum nanocatalyst to three distinct graphenic surfaces. At ambient temperature, hydrogenation and dehydrogenation are reversible in the combined presence of an active catalyst and oxygen heteroatoms. Hydrogenation apparently occurs through surface diffusion in a chemisorbed state, while dehydrogenation requires diffusion of the chemisorbed species back to an active catalyst

Global Outreach Using a Systematic, Competency-Based Training Paradigm for Inguinal Hernioplasty

IMPORTANCE Sustainable, capacity-building educational collaborations are essential to address the global burden of surgical disease. OBJECTIVE To assess an international, competency-based training paradigm for hernia surgery in underserved countries. DESIGN, SETTING, AND PARTICIPANTS In this prospective, observational study performed from November 1, 2013, through October 31, 2015, at 16 hospitals in Brazil, Ecuador, Haiti, Paraguay, and the Dominican Republic, surgeons completed initial training programs in hernia repair, underwent interval proficiency assessments, and were appointed regional trainers. Competency-based evaluations of technical proficiency were performed using the Operative Performance Rating Scale (OPRS). Maintenance of proficiency was evaluated by video assessments 6 months after training. Certified trainees received incentives to document independent surgical outcomes after training. MAIN OUTCOMES AND MEASURES An OPRS score of 3.0 (scale of 1 [poor] to 5 [excellent]) indicated proficiency. Secondary outcomes included initial vs final scores by country, scores among surgeons trained by the regional trainers (second-order trainees), interval scores 6 months after training, and postoperative complications. RESULTS A total of 20 surgeon trainers, 81 local surgeons, and 364 patients (343 adult, 21 pediatric) participated in the study (mean [SD] age, 47.5 [16.3] years; age range, 16-83 years). All 81 surgeons successfully completed the program, and all 364 patients received successful operations. Mean (SD) OPRS scores improved from 4.06 (0.87) before the initial training program to 4.52 (0.57) after training (P < .001). No significant variation was found by country in final scores. On trainee certification, 20 became regional trainers. The mean (SD) OPRS score among 53 second-order trainees was 4.34 (0.68). After 6-month intervals, the mean (SD) OPRS score among participating surgeons was 4.34 (0.55). The overall operative complication rate during training series was 1.1%. CONCLUSIONS AND RELEVANCE Competency-based training helps address the global burden of surgical disease. The OPRS establishes an international standard of technical assessment. Additional studies of long-Term surgeon trainer proficiency, community-specific quality initiatives, and expansion to other operations are warranted. JAMA Surg