Predicting lung cancer prior to surgical resection in patients with lung nodules.

BACKGROUND: Existing predictive models for lung cancer focus on improving screening or referral for biopsy in general medical populations. A predictive model calibrated for use during preoperative evaluation of suspicious lung lesions is needed to reduce unnecessary operations for a benign disease. A clinical prediction model (Thoracic Research Evaluation And Treatment [TREAT]) is proposed for this purpose. METHODS: We developed and internally validated a clinical prediction model for lung cancer in a prospective cohort evaluated at our institution. Best statistical practices were used to construct, evaluate, and validate the logistic regression model in the presence of missing covariate data using bootstrap and optimism corrected techniques. The TREAT model was externally validated in a retrospectively collected Veteran Affairs population. The discrimination and calibration of the model was estimated and compared with the Mayo Clinic model in both the populations. RESULTS: The TREAT model was developed in 492 patients from Vanderbilt whose lung cancer prevalence was 72% and validated among 226 Veteran Affairs patients with a lung cancer prevalence of 93%. In the development cohort, the area under the receiver operating curve (AUC) and Brier score were 0.87 (95% confidence interval [CI], 0.83-0.92) and 0.12, respectively compared with the AUC 0.89 (95% CI, 0.79-0.98) and Brier score 0.13 in the validation dataset. The TREAT model had significantly higher accuracy (p < 0.001) and better calibration than the Mayo Clinic model (AUC = 0.80; 95% CI, 75-85; Brier score = 0.17). CONCLUSION: The validated TREAT model had better diagnostic accuracy than the Mayo Clinic model in preoperative assessment of suspicious lung lesions in a population being evaluated for lung resection.

Musculoskeletal occupational injury among surgeons: effects for patients, providers, and institutions.

BACKGROUND: The aim of this study was to determine the risk of occupational musculoskeletal injury during a surgeon's career and the effects of these injuries for patients, providers, and institutions. We hypothesized that surgeons have occupational injuries, which affect work performance. MATERIALS AND METHODS: Electronic RedCAP surveys on workplace injury were distributed statewide via e-mail to the members of the Tennessee chapter of the American College of Surgeons. Descriptive statistics were used to analyze survey data. RESULTS: A total of 260 of 793 surveys (33%) were returned. Forty percent of surgeons sustained ≥ 1 injuries in the workplace. Although 50% of injured surgeons received medical care for their most recent injuries, only 20% of these injuries were reported to their institution. Twenty-two percent of injured surgeons missed work and 35% performed fewer operations while they were recovering from their injury. Fifty-three percent of injured surgeons reported that pain from their injury had a minimal or moderate effect on their performance in the operating room. CONCLUSIONS: Surgeons appear to be at moderate risk for occupation-related injuries. The low rate of institutional reporting for these injuries is concerning, as this is a required step to access institutional support once injured. Surgeon injury results in lost productivity due to missed workdays and may impact the quality of surgical care because of performance issues while recovering from injury.

TR3 modulates platinum resistance in ovarian cancer.

In metastatic ovarian cancer, resistance to platinum chemotherapy is common. Although the orphan nuclear receptor TR3 (nur77/NR4A1) is implicated in mediating chemotherapy-induced apoptosis in cancer cells, its role in ovarian cancer has not been determined. In an ovarian cancer tissue microarray, TR3 protein expression was elevated in stage I tumors, but downregulated in a significant subset of metastatic tumors. Moreover, TR3 expression was significantly lower in platinum-resistant tumors in patients with metastatic disease, and low TR3 staining was associated with poorer overall and progression-free survival. We have identified a direct role for TR3 in cisplatin-induced apoptosis in ovarian cancer cells. Nucleus-to-cytoplasm translocation of TR3 was observed in cisplatin-sensitive (OVCAR8, OVCAR3, and A2780PAR) but not cisplatin-resistant (NCI/ADR-RES and A2780CP20) ovarian cancer cells. Immunofluorescent analyses showed clear overlap between TR3 and mitochondrial Hsp60 in cisplatin-treated cells, which was associated with cytochrome c release. Ovarian cancer cells with stable shRNA- or transient siRNA-mediated TR3 downregulation displayed substantial reduction in cisplatin effects on apoptotic markers and cell growth in vitro and in vivo. Mechanistic studies showed that the cisplatin-induced cytoplasmic TR3 translocation required for apoptosis induction was regulated by JNK activation and inhibition of Akt. Finally, cisplatin resistance was partially overcome by ectopic TR3 overexpression and by treatment with the JNK activator anisomycin and Akt pathway inhibitor, wortmannin. Our results suggest that disruption of TR3 activity, via downregulation or nuclear sequestration, likely contributes to platinum resistance in ovarian cancer. Moreover, we have described a treatment strategy aimed at overcoming platinum resistance by targeting TR3.

Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group.

OBJECTIVE: Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism. MEASUREMENTS AND METHODS: Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome. RESULTS: From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy. CONCLUSIONS: Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.