Research Spotlight

Rizk, D. V., A. L. Silva, P. E. Pergola, R. Toto, D. G. Warnock, M. P. Chin, A. Goldsberry, M. O’Grady, C. J. Meyer and P. A. McCullough (2019). “Effects of Bardoxolone Methyl on Magnesium in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease.” Cardiorenal Med Jun 6: 1-10. [Epub ahead of print].

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BACKGROUND: Treatment with bardoxolone methyl (Bard) in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate with concurrent reductions in serum magnesium. We analyzed data from several trials to characterize reductions in magnesium with Bard. METHODS: BEACON randomized patients (n = 2,185) with type 2 diabetes (T2DM) and stage 4 chronic kidney disease (CKD) 1:1 to receive Bard (20 mg) or placebo once daily. In a separate open-label study, magnesium levels from 24-hour urine and sublingual epithelial cell samples were analyzed in patients with stage 3b-4 CKD and T2DM administered 20 mg Bard for 56 consecutive days. RESULTS: BEACON patients randomized to Bard experienced significant reductions in serum magnesium from baseline relative to patients randomized to placebo (-0.17 mEq/L, 95% CI -0.18 to -0.60 mEq/L; p < 0.001). A separate study showed intracellular and urinary magnesium levels were unchanged with Bard treatment. CONCLUSIONS: Bard treatment results in significant decreases in serum magnesium that are not associated with changes in intracellular and urinary magnesium levels, indicating that magnesium decreases are not due to renal magnesium wasting or total body magnesium depletion. Importantly, the decreases in serum magnesium with Bard are not associated with adverse effects on QT interval.

Reich, K., P. Rich, C. Maari, R. Bissonnette, C. Leonardi, A. Menter, A. Igarashi, P. Klekotka, D. Patel, J. Li, J. Tuttle, M. Morgan-Cox, E. Edson-Heredia, S. Friedrich and K. Papp (2019). “Efficacy and safety of mirikizumab (LY3074828) in the treatment of moderate-to-severe plaque psoriasis: results from a randomized phase II study.” Br J Dermatol 181(1): 88-95.

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BACKGROUND: Inhibiting interleukin (IL)-23 in patients with psoriasis has demonstrated high levels of skin clearance. OBJECTIVES: To investigate, in a phase II (AMAF; NCT02899988), multicentre, double-blind trial, the efficacy and safety of three doses of mirikizumab (LY3074828), a p19-directed IL-23 antibody, vs. placebo in patients with moderate-to-severe plaque psoriasis. METHODS: Adult patients were randomized 1 : 1 : 1 : 1 to receive placebo (n = 52), mirikizumab 30 mg (n = 51), mirikizumab 100 mg (n = 51) or mirikizumab 300 mg (n = 51) subcutaneously at weeks 0 and 8. The primary objective was to evaluate the superiority of mirikizumab over placebo in achieving a 90% improvement in the Psoriasis Area and Severity Index (PASI 90) response at week 16. Comparisons were done using logistic regression analysis with treatment, geographical region and previous biological therapy in the model. Missing data were imputed as nonresponses. RESULTS: Ninety-seven per cent of patients completed the first 16 weeks of the study. The primary end point was met for all mirikizumab dose groups vs. placebo, with PASI 90 response rates at week 16 of 0%, 29% (P = 0.009), 59% (P < 0.001) and 67% (P < 0.001) for patients receiving placebo, and mirikizumab 30 mg, 100 mg and 300 mg, respectively. There were two (1%) serious adverse events in mirikizumab-treated patients vs. one (2%) in a placebo-group patient. CONCLUSIONS: At week 16, 67% of patients treated with mirikizumab 300 mg at 8-week intervals achieved PASI 90. The percentage of patients reporting at least one treatment-emergent adverse event was similar among patients treated with placebo or mirikizumab.

Ramsay, M. A. (2019). “Postoperative Pain Management: Is the Surgical Team Approach Finally Getting It Right?” Ann Surg Jun 7. [Epub ahead of print].

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When the surgical team approach is used consistently and evidence-based protocols for preoperative, intraoperative, and postoperative pain management are employed, together with center specific data collection, significant improvements in patient care can be obtained. Regular review of the data collected is needed so that improvements may be initiated where indicated and also to monitor compliance with the protocols. When goal-directed fluid therapy and the use of nonopioid analgesics such as low-dose intravenous ketamine, oral acetaminophen, and gabapentin, are used together with maintaining normothermia, omitting nasogastric tubes and surgical drains, early mobilization, and early recovery may be consistently obtained. More importantly, perioperative opioids may be severely limited or totally avoided, resulting in less postoperative nausea and vomiting and early return of bowel function.22 The ERP protocol must also contain guidelines for prescribing pain medications at discharge. This again should be multimodal with a goal of limited or zero opioids. The overall goal is safe, effective care of our patients, good analgesia, early mobilization, avoiding or minimizing opioids, and early discharge home with minimal complications. This will result in both improved patient experience and reduced hospital costs. (Excerpt from online text of article in press; no abstract available.)

Raj, S. D., J. Phillips, T. S. Mehta, L. M. Quintana, M. D. Fishman, V. Dialani and P. J. Slanetz (2019). “Management of BIRADS 3, 4A, and 4B Lesions Diagnosed as Pure Papilloma by Ultrasound-Guided Core Needle Biopsy: Is Surgical Excision Necessary?” Acad Radiol 26(7): 909-914.

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RATIONALE AND OBJECTIVES: There is lack of consensus on managing papillomas due to varied upgrade rates in the literature related to variability in the studied populations. We specifically studied upgrade rates of pure papilloma diagnosed with ultrasound core biopsy (UCB) using spring-loaded (SLB) and vacuum-assisted (VAB) biopsy devices in patients with low-to-intermediate pre-test probability for malignancy on imaging. MATERIALS & METHODS: From 01/01/2008 to 06/30/2016, 227 patients with 248 pure papillomas classified as BI-RADS 3, 4a, and 4b were diagnosed by UCB and underwent surgical excision or clinical and/or imaging follow-up. Imaging features, biopsy device, and final pathology were documented. RESULTS: 177 lesions were biopsied with SLB (14-gauge) and 71 lesions with VAB (9-13 gauges). At surgery, upgrade rates to high-risk lesions and malignancy for SLB were 14.3% (22/154) and 1.9% (3/154), and for VAB were 3.5% (2/57) and 0% (0/57), respectively (p < 0.05). The combined surgical upgrade rate to high-risk lesions and malignancy was 11.4% (24/211) and 1.4% (3/211), respectively. The overall upgrade rate (including surgical and clinical and/or imaging follow-up) to high-risk lesions and malignancy was 9.7% (24/248) and 1.2% (3/248), respectively. No ultrasound features were predictive of upgrade. Rates of complete excision were 7.1% (11/154) for SLB and 19.3% (11/57) for VAB (p < 0.05). CONCLUSION: BI-RADS 3, 4a, or 4b masses biopsied with UCB revealed pure papilloma upgrade to malignancy in less than 2% of cases. SLB was associated with greater upgrades compared with VAB. Therefore, follow-up imaging is a reasonable alternative to excision, particular in those sampled by VAB. Excision could be considered if the diagnosis of a high-risk lesion would change clinical management.

Plichta, J. K., M. L. Sebastian, L. A. Smith, C. S. Menendez, A. T. Johnson, S. M. Bays, D. M. Euhus, E. J. Clifford, M. Jalali, S. H. Kurtzman, W. A. Taylor and K. S. Hughes (2019). “Germline Genetic Testing: What the Breast Surgeon Needs to Know.” Ann Surg Oncol 26(7): 2184-2190.

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PURPOSE: The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. METHODS: A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. RESULTS: Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. RECOMMENDATIONS: Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.