Coan, Kathryn E.

Objective: The objective was to assess processes of care for patients with diabetes undergoing elective surgery. Methods: A retrospective review of medical records was conducted to determine frequency of perioperative glucose monitoring, changes in glucose control, and treatment of intraoperative hyperglycemia. Results: A total of 268 patients underwent 287 elective procedures. Mean age was 67 years, 63% were men, 97% had type 2 diabetes, and most (57%) were treated with oral hypoglycemic agents. Average perioperative time was approximately 8 h. Mean preoperative hemoglobin A1c was 7.0%; however, this value was checked in only 52% of cases. A glucose measurement was obtained in 89% of cases in the preoperative area and in 87% in the postanesthesia care unit, but in only 33% of cases did a value get checked intraoperatively. Average glucose was 139 mg/dl preoperatively, increasing to 166 mg/dl postoperatively ( p <.001). Glucose levels increased regardless of type of outpatient medical therapy used to treat hyperglycemia, except for those on combination oral agents plus insulin ( p =.06). Conclusions: These data indicate suboptimal documentation of outpatient hemoglobin A1c. Intraoperative glucose monitoring seldom occurred, despite prolonged periods under anesthesia and perioperative deterioration of glycemic control. Standards need to be developed and interventions are needed to enhance management of diabetes patients undergoing elective procedures.

Objective: Our objective was to assess the application of insulin regimens in surgical postoperative patients with diabetes. Methods: A chart review was conducted of patients with diabetes who were hospitalized postoperatively between January 1 and April 30, 2011. Analysis was restricted to patients hospitalized for ≥3 days and excluded cases with an endocrinology consult. Insulin regimens were categorized as “basal plus short acting,” “short acting only,” or “none,” and the pattern of use was evaluated by hyperglycemia severity according to tertiles of both mean glucose and the number of glucose measurements >180 mg/dl. Results: Among cases selected for analysis ( n = 119), examination of changes in insulin use based on tertiles of mean glucose showed that use of basal plus short-acting insulin increased from 10% in the lowest tertile (mean glucose, 120 mg/dl) to 18% in the highest tertile (mean glucose, 198 mg/dl; p < .01); however, 70% of patients in the highest tertile continued to receive short-acting insulin only, with 12% receiving no insulin. Intensification of insulin to a basal plus short-acting regimen was also seen when changes were evaluated by the number of measurements >180 mg/dl ( p < .01), but 70% and 12% of patients in the highest tertile still remained only on short-acting insulin or received no insulin, respectively. Conclusions: Use of basal plus short-acting insulin therapy increased with worsening hyperglycemia, but many cases did not have therapy intensified to the recommended insulin regimen—evidence of clinical inertia. Strategies should be devised to overcome inpatient clinical inertia in the treatment of postoperative patients with diabetes.

We describe the successful percutaneous treatment of acute-on-chronic IVC thrombosis 30 years following previous placement of Adams-DeWeese clip.

We present a 33-year-old dialysis-dependent female who presented with new onset split second heart sound. Following a failed left upper extremity dialysis fistula, a right upper extremity hemodialysis reliable outflow (HeRO) graft was performed in 2011. Her subsequent cadaveric renal transplant had delayed function necessitating concurrent use of hemodialysis. However, as renal function improved, hemodialysis was discontinued. Two weeks following transplantation, the HeRO graft occluded. Subsequent clinical and radiological assessment confirmed widespread pulmonary emboli. Following cessation of hemodialysis and subsequent HeRO graft occlusion, removal was deemed appropriate to reduce further thromboembolic phenomenon. Right atrial thrombi are complications associated with central venous catheters. However, their actual incidence varies significantly. Right heart thromboemboli are associated with a 4% to 6% pulmonary embolism rate. Katzman et al assessed 38 patients who underwent HeRO graft and reported 1 (2.6%) patient with right atrial emboli and likely pulmonary embolism. Although thrombotic complications remain rare, consideration of graft removal should always be evaluated particularly in the absence of an alternative thrombotic source.

Abstract Adrenocortical carcinoma (ACC) is an aggressive cancer with a 5-year survival rate of 20-30%. Mitotane is the only approved drug for the treatment of patients with ACC. It often carries significant toxicities which result in the discontinuation of treatment. There are no approved second line therapies. The increased incidence of ACC in the cancer predisposition syndrome, Li-Fraumeni, suggests the involvement of the p53 pathway in ACC pathogenesis. Our analysis of the gene expression profiles of 19 ACC samples identified dysregulation of the G2/M transition and the activity of the p53 modulator, MDM2 as important in ACC pathogenesis. Polo-like kinase-1 (PLK1) is involved in the G2/M transition and acts to promote MDM2 activity through its phosphorylation. We observed that PLK1 inhibition by siRNA results in up to a 70% reduction in viability in the ACC cell lines SW-13 and H295R. Therefore, we studied PLK1 inhibition as a potential therapeutic strategy. We used the small molecule inhibitor, BI-2536, to inhibit PLK1 function in SW-13 and H295R. Drug-dose response curves demonstrated that both cell lines are sensitive to pharmacological inhibition of PLK1 (IC50 doses of 0.0094815 μM and 0.062805 μM for SW-13 and H295R, respectively.) Murine xenograft studies demonstrated that BI-2536 resulted in a statistically significant reduction in tumor growth in SW-13 but not H295R. Examination of p53 protein levels in the presence of the drug showed a dose-dependent reduction in p53 levels in SW-13, which carries a homozygous p53 mutation. The same was not true in H295R, which is p53 wild-type. To test the hypothesis that BI-2536 was decreasing mutant p53 levels by promoting its proteasomal degradation, both cell lines were treated with previously determined inhibitory concentrations of BI-2536, either alone or in combination with the proteasome inhibitor, MG132. Western blot analysis showed recovery of p53 protein when cells were concomitantly treated with MG132, supporting a role for BI-2536 as a regulator of proteasomal degradation. Both ACC cell lines are relatively insensitive to MDM2 inhibition by nutlin-3 (NCI60 GI50 values range from ∼4 uM to ∼2 uM versus ACC cell lines @13-15uM), possibly because PLK1 stimulates MDM2 and renders nutlin-3 ineffective. We therefore assessed the ability of BI-2536 to sensitize ACC cell lines to the effects of the MDM2 inhibitor. BI-2636 did show synergy with nutlin-3, shifting the IC50 in SW-13 from 19.78 μM to 6.45 μM and from 12.75 μM to 2.84 μM in H295R. These results demonstrate that inhibition of PLK1 alone or in combination with an MDM2 inhibitor warrants further investigation as a treatment for patients with ACC. Cells with mutant p53 are more sensitive to the growth inhibitory effects of BI-2536. In the context of wild-type p53, the combined inhibition of both PLK1 and MDM2 results in loss of viability. Further clinical development of PLK1 as a target should take p53 mutation status into account. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 978. doi:1538-7445.AM2012-978