Research Spotlight

Nguyen, V. Q., J. L. Mays, M. Lang, Y. Wu, T. Dassopoulos, M. Regueiro, A. Moss, D. D. Proctor and D. Sorrentino (2017). “Knowledge gaps in the management of postoperative crohn’s disease: A us national survey.” Dig Dis Sci: 2017 Nov [Epub ahead of print].

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BACKGROUND: Postoperative recurrence (POR) of Crohn’s disease (CD) is common. Guidelines on POR management have recently been issued, but clinical practice may vary. AIMS: To examine the current clinical practice of POR management in the USA METHODS: A web-based survey was sent to all members of the American Gastroenterological Association and the American College of Gastroenterology. The survey consisted of multiple-choice questions with clinical scenarios to assess how participants manage POR. RESULTS: A total of 189 responses were received from practices in 34 states. 44% of participants were from academic settings. The median number of CD patients seen each month was 20-30 patients per participant. The majority of participants considered smoking, prior intestinal surgery, penetrating disease, perianal fistula, early disease onset, and long extent of disease as high-risk factors for POR. To diagnose and grade endoscopic recurrence, 57% of participants used an endoscopic scoring system; 86% defined clinical recurrence using a combination of symptoms and endoscopic findings; and 79% of participants routinely performed colonoscopy after surgery. In high-risk patients, 65% offered medical prophylaxis-most often biologics and/or immunomodulators-immediately after surgery, while 34% offered medical prophylaxis regardless of the patient’s risk of POR. 64% of participants never stopped medical prophylaxis once initiated. CONCLUSIONS: Most gastroenterologists routinely perform colonoscopy to guide POR management. The majority of these providers continue medical prophylaxis indefinitely regardless of subsequent endoscopic findings. Further research is needed to determine the risks and benefits of continuing versus deescalating therapy in patients with potentially surgically induced remission.

O’Gara, P. T., T. M. Sundt, M. A. Acker, T. E. David, R. E. Michler, M. A. Borger, G. Ailawadi, V. H. Thourani, A. M. Gillinov, R. J. Damiano, M. J. Mack, R. Lee, E. A. Rose, T. J. Gardner, M. A. Miller, R. D. Weisel and A. C. Gelijns (2017). “The cardiothoracic surgical trials network: Implications for clinical practice.” J Thorac Cardiovasc Surg 154(6): 1938-1956.

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Background: Postoperative recurrence (POR) of Crohn’s disease (CD) is common. Guidelines on POR management have recently been issued, but clinical practice may vary. Aims:To examine the current clinical practice of POR management in the USA Methods: A web-based survey was sent to all members of the American Gastroenterological Association and the American College of Gastroenterology. The survey consisted of multiple-choice questions with clinical scenarios to assess how participants manage POR. Results: A total of 189 responses were received from practices in 34 states. 44% of participants were from academic settings. The median number of CD patients seen each month was 20–30 patients per participant. The majority of participants considered smoking, prior intestinal surgery, penetrating disease, perianal fistula, early disease onset, and long extent of disease as high-risk factors for POR. To diagnose and grade endoscopic recurrence, 57% of participants used an endoscopic scoring system; 86% defined clinical recurrence using a combination of symptoms and endoscopic findings; and 79% of participants routinely performed colonoscopy after surgery. In high-risk patients, 65% offered medical prophylaxis—most often biologics and/or immunomodulators—immediately after surgery, while 34% offered medical prophylaxis regardless of the patient’s risk of POR. 64% of participants never stopped medical prophylaxis once initiated. Conclusions: Most gastroenterologists routinely perform colonoscopy to guide POR management. The majority of these providers continue medical prophylaxis indefinitely regardless of subsequent endoscopic findings. Further research is needed to determine the risks and benefits of continuing versus deescalating therapy in patients with potentially surgically induced remission.

O’Shaughnessy, J., K. Petrakova, G. S. Sonke, P. Conte, C. L. Arteaga, D. A. Cameron, L. L. Hart, C. Villanueva, E. Jakobsen, J. T. Beck, D. Lindquist, F. Souami, S. Mondal, C. Germa and G. N. Hortobagyi (2017). “Ribociclib plus letrozole versus letrozole alone in patients with de novo hr+, her2- advanced breast cancer in the randomized monaleesa-2 trial.” Breast Cancer Res Treat: 2017 Nov [Epub ahead of print].

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PURPOSE: Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. METHODS: Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. RESULTS: Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. CONCLUSIONS: Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

Packer, M. (2017). “Early worsening of renal function after treatment with antihyperglycemic drugs: A consistent finding in large-scale trials.” Am J Med: 2017 Nov [Epub ahead of print].

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Prolonged hyperglycemia in type 2 diabetes exerts adverse structural and functional effects on the kidney, and sustained lowering of blood glucose for a decade or longer has been shown to reduce the risk of progression to end-stage renal disease. 1 However, during the first months or years of treatment with an antihyperglycemic drug, patients may experience worsening of renal function regardless of the agent used to lower blood glucose. There is minimal recognition of this phenomenon in the medical literature. The most persuasive evidence supporting the occurrence of early worsening of renal function after initiation of treatment with antidiabetic drugs is derived from randomized controlled clinical trials with different antihyperglycemic agents. Sequential changes in estimated glomerular filtration rate (or in serum creatinine) have been reported in 5 large-scale trials completed since regulatory agencies issued a new guidance on diabetes in 2008. 2

Packer, M. (2017). “Early worsening of renal function after treatment with antihyperglycemic drugs: A consistent finding in large-scale trials.” Am J Med: 2017 Nov [Epub ahead of print].

Full text of this article.

Prolonged hyperglycemia in type 2 diabetes exerts adverse structural and functional effects on the kidney, and sustained lowering of blood glucose for a decade or longer has been shown to reduce the risk of progression to end-stage renal disease. 1 However, during the first months or years of treatment with an antihyperglycemic drug, patients may experience worsening of renal function regardless of the agent used to lower blood glucose. There is minimal recognition of this phenomenon in the medical literature. The most persuasive evidence supporting the occurrence of early worsening of renal function after initiation of treatment with antidiabetic drugs is derived from randomized controlled clinical trials with different antihyperglycemic agents. Sequential changes in estimated glomerular filtration rate (or in serum creatinine) have been reported in 5 large-scale trials completed since regulatory agencies issued a new guidance on diabetes in 2008. 2