Research Spotlight

Posted April 15th 2016

Challenges in the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with brain metastases.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy, M.D.

Liu, M. C., J. Cortes and J. O’Shaughnessy (2016). “Challenges in the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer with brain metastases.” Cancer Metastasis Rev. Mar 29. [Epub ahead of print]

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Brain metastases are a major cause of morbidity and mortality for women with hormone receptor (HR)-positive breast cancer, yet little is known about the optimal treatment of brain disease in this group of patients. Although these patients are at lower risk for brain metastases relative to those with HER2-positive and triple-negative disease, they comprise the majority of women diagnosed with breast cancer. Surgery and radiation continue to have a role in the treatment of brain metastases, but there is a dearth of effective systemic therapies due to the poor penetrability of many systemic drugs across the blood-brain barrier (BBB). Additionally, patients with brain metastases have long been excluded from clinical trials, and few studies have been conducted to evaluate the safety and effectiveness of systemic therapies specifically for the treatment of HER2-negative breast cancer brain metastases. New approaches are on the horizon, such as nanoparticle-based cytotoxic drugs that have the potential to cross the BBB and provide clinically meaningful benefits to patients with this life-threatening consequence of HR-positive breast cancer.


Posted April 15th 2016

Assessing Trends in Tobacco Cessation in Diverse Patient Populations.

Elisa L. Priest Dr.P.H.

Elisa L. Priest, Dr.P.H.

Stevens, V. J., L. I. Solberg, S. R. Bailey, S. E. Kurtz, M. A. McBurnie, E. L. Priest, J. E. Puro, R. J. Williams, S. P. Fortmann and B. L. Hazlehurst (2016). “Assessing Trends in Tobacco Cessation in Diverse Patient Populations.” Nicotine Tob Res 18(3): 275-280.

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INTRODUCTION: This study examined change in tobacco use over 4 years among the general population of patients in six diverse health care organizations using electronic medical record data. METHODS: The study cohort (N = 34 393) included all patients age 18 years or older who were identified as smokers in 2007, and who then had at least one primary care visit in each of the following 4 years. RESULTS: In the 4 years following 2007, this patient cohort had a median of 13 primary care visits, and 38.6% of the patients quit smoking at least once. At the end of the fourth follow-up year, 15.4% had stopped smoking for 1 year or more. Smokers were more likely to become long-term quitters if they were 65 or older (OR = 1.32, 95% CI = [1.16, 1.49]), or had a diagnoses of cancer (1.26 [1.12, 1.41]), cardiovascular disease (1.22 [1.09, 1.37]), asthma (1.15 [1.06, 1.25]), or diabetes (1.17 [1.09, 1.27]). Characteristics associated with lower likelihood of becoming a long-term quitter were female gender (0.90 [0.84, 0.95]), black race (0.84 [0.75, 0.94]) and those identified as non-Hispanic (0.50 [0.43, 0.59]). CONCLUSIONS: Among smokers who regularly used these care systems, one in seven had achieved long-term cessation after 4 years. This study shows the practicality of using electronic medical records for monitoring patient smoking status over time. Similar methods could be used to assess tobacco use in any health care organization to evaluate the impact of environmental and organizational programs.


Posted April 15th 2016

The effect of wavelength on endothermal heat-induced thrombosis incidence after endovenous laser ablation.

William P. Shutze M.D.

William P. Shutze, M.D.

Shutze, W. P., K. Kane, T. Fisher, Y. Doud, G. Lassiter, R. Leuking, E. Nguyen and W. P. Shutze, Jr. (2016). “The effect of wavelength on endothermal heat-induced thrombosis incidence after endovenous laser ablation.” J Vasc Surg Venous Lymphat Disord 4(1): 36-44.

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OBJECTIVE: We hypothesized that the incidence of endothermal heat-induced thrombosis (EHIT) depends on the laser wavelength used in endovenous laser ablation (EVLA) of the saphenous veins. METHODS: We identified patients undergoing EVLA in our office from 2005 to 2014 with an 810-nm (hemoglobin-specific) or 1470-nm (water-specific) laser. We reviewed the records for age, sex, body mass index, Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) class, vein diameter, vein(s) treated, adjunctive phlebectomy, energy delivered, laser pullback times, and EHIT (closure level >/=3) development. The Fisher exact test and Pearson chi(2) test were used to evaluate the association between EHIT and the categoric variables. Logistic regression was used to evaluate the relationship between EHIT and the continuous variables. RESULTS: There were 1439 veins ablated in 1109 patients (769 female, 340 male). The great saphenous vein (GSV) was treated in 1332, the small saphenous vein (SSV) in 78, and both in 29 (22 procedures on accessory veins were excluded). The CEAP C class for these patients was 1 in 0, 2 in 616, 3 in 522, 4 in 150, 5 in 51, and 6 in 98, and was not recorded in 2. EHIT occurred in 76 cases (5.28%), in 73 after GSV ablation and in three after SSV ablation. The 810-nm laser was used in 1144 procedures, and EHIT developed in 69 patients (6.0%). The 1470-nm laser was used in 295 procedures, with EHIT developing in seven patients (2.4%; P = .0122 by Fisher exact test). The average energy delivered to the EHIT group (3517 +/- 1998.1 J) was higher than for the non-EHIT group (2825.1 +/- 1491.2 J; P = .0002). The average vein diameter was larger in the EHIT group (9.3 +/- 3.8 mm) than in the non-EHIT group (7.2 +/- 3.3 mm; P = .0001). EHIT occurred in 59 of 837 cases (6.6%) undergoing simultaneous stab phlebectomy compared with 17 of 525 cases (3.1%) undergoing only EVLA (P = .0049). Statistical analysis confirmed the association between EHIT and CEAP class was significant (P = .0001). No differences were seen for age, body mass index, sex, combined bilateral, and multiple or simultaneous GSV and SSV ablations between the two groups. A multivariate analysis confirmed that CEAP class, vein diameter, adjunctive phlebectomy, and laser wavelength were indeed risk factors for post-EVLA EHIT and that energy delivered and pullback time were not. CONCLUSIONS: Water-specific laser fiber wavelength (1470 nm) reduces the risk of EHIT compared with a hemoglobin-specific wavelength (810 nm). CEAP class, simultaneous phlebectomy, and vein diameter >7.5 mm are associated with increased risk of EHIT after EVLA.


Posted April 15th 2016

Essential phospholipids prevent islet damage induced by proinflammatory cytokines and hypoxic conditions.

Marlon F. Levy M.D.E

Marlon F. Levy, M.D.E

Shahbazov, R., M. A. Kanak, M. Takita, F. Kunnathodi, O. Khan, N. Borenstein, M. C. Lawrence, M. F. Levy and B. Naziruddin (2016). “Essential phospholipids prevent islet damage induced by proinflammatory cytokines and hypoxic conditions.” Diabetes Metab Res Rev 32(3): 268-277.

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BACKGROUND: The pancreatic islet damage that occurs through an inflammatory response and hypoxia after infusion is a major hurdle in islet transplantation. Because essential phospholipids (EPL) have been shown to exhibit anti-inflammatory properties in liver disease, we analysed their protective effect on islets in inflammatory or hypoxic conditions. METHODS: We evaluated the viability of mouse and human islets cultured with cytokines or in hypoxic conditions for 48 h and measured cytokine expression in islets by quantitative polymerase chain reaction. We then employed an in vivo mouse assay, transplanting a marginal dose of human islets treated with or without EPL into the subcapsule of the kidney in diabetic nude mice and determining the cure rate. RESULTS: The viability of mouse and human islets damaged by cytokines was significantly improved by supplementation of EPL in the culture (p = 0.003 and <0.001 for mouse and human islets respectively). EPL significantly inhibited intracellular expression of IL-1beta and IL-6 in cytokine-damaged human islets (p < 0.001). The viability of human islets in hypoxic conditions was significantly better when treated with EPL (p < 0.001). In the in vivo mouse assay, the EPL-treated islet group had a higher cure rate than the untreated control, with marginal statistical significance (75 and 17% respectively, p = 0.07). CONCLUSIONS: EPL could be a potent agent to protect islets from inflammatory and hypoxic conditions after isolation procedures. Further studies to clarify the effect of EPL in islet transplantation are warranted.


Posted April 15th 2016

Multicenter validation of American Association for the Surgery of Trauma grading system for acute colonic diverticulitis and its use for emergency general surgery quality improvement program.

Shahid Shafi M.D.

Shahid Shafi, M.D.

Shafi, S., E. L. Priest, M. L. Crandall, C. S. Klekar, A. Nazim, M. Aboutanos, S. Agarwal, B. Bhattacharya, N. Byrge, T. S. Dhillon, D. J. Eboli, D. Fielder, O. Guillamondegui, O. Gunter, K. Inaba, N. T. Mowery, R. Nirula, S. E. Ross, S. A. Savage, K. M. Schuster, R. K. Schmoker, S. Siboni, N. Siparsky, M. D. Trust, G. H. Utter, J. Whelan, D. V. Feliciano and G. Rozycki (2016). “Multicenter validation of American Association for the Surgery of Trauma grading system for acute colonic diverticulitis and its use for emergency general surgery quality improvement program.” J Trauma Acute Care Surg 80(3): 405-411.

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BACKGROUND: The American Association for the Surgery of Trauma (AAST) has developed a new grading system for uniform description of anatomic severity of emergency general surgery (EGS) diseases, ranging from Grade I (mild) to Grade V (severe). The purpose of this study was to determine the relationship of AAST grades for acute colonic diverticulitis with patient outcomes. A secondary purpose was to propose an EGS quality improvement program using risk-adjusted center outcomes, similar to National Surgical Quality Improvement Program and Trauma Quality Improvement Program methodologies. METHODS: This was a retrospective study of 1,105 patients (one death) from 13 centers. At each center, two reviewers (blinded to each other’s assignments) assigned AAST grades. Interrater reliability was measured using kappa coefficient. Relationship between AAST grade and clinical events (complications, intensive care unit use, surgical intervention, and 30-day readmission) as well as length of stay was measured using regression analyses to control for age, comorbidities, and physiologic status at the time of admission. Final model was also used to calculate observed-to-expected (O-E) ratios for adverse outcomes (death, complications, readmissions) for each center. RESULTS: Median age was 54 years, 52% were males, 43% were minorities, and 22% required a surgical intervention. Almost two thirds had Grade I or II disease. There was a high level of agreement for grades between reviewers (kappa = 0.81). Adverse events increased from 13% for Grade I, to 18% for Grade II, 28% for Grade III, 44% for Grade IV, and 50% for Grade V. Regression analysis showed that higher disease grades were independently associated with all clinical events and length of stay, after adjusting for age, comorbidities, and physiology. O-E ratios showed statistically insignificant variations in risk of death, complications, or readmissions. CONCLUSION: AAST grades for acute colonic diverticulitis are independently associated with clinical outcomes and resource use. EGS quality improvement program methodology that incorporates AAST grade, age, comorbidities, and physiologic status may be used for measuring quality of EGS care. High-quality EGS registries are essential for developing meaningful quality metrics. LEVEL OF EVIDENCE: Prognostic study, level V.