Citations

Coronary artery aneurysm is defined as a coronary dilation that exceeds the diameter of adjacent segments or the diameter of the patient's largest normal coronary vessel by 1.5×. It is an uncommon disease that has been diagnosed with increasing frequency since the widespread appearance of coronary angiography. The published incidence varies from 1.5% to 5%, suggesting male dominance and a predilection for the right coronary artery. Although several causes have been described, atherosclerosis accounts for ≥50% of coronary aneurysms in adults. Reported complications include thrombosis and distal embolization, rupture, and vasospasm, causing ischemia, heart failure, or arrhythmias. The natural history and prognosis remain unknown, as definitive data are scarce. Controversies persist regarding the use of medical management (antithrombotic therapy) or interventional/surgical procedures. Only some case reports or small case series are available about this condition. The Coronary Artery Aneurysm Registry (CAAR; http://www.ClinicalTrials.gov NCT02563626) is a multicenter international ambispective registry that aims to provide insights on anatomic, epidemiologic, and clinical aspects of this substantially unknown entity. In addition, the registry will assess management strategies (conservative, interventional, or surgical) and their short‐ and long‐term results in a large cohort of patients.Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT02563626.

LBA385 Background: Regorafenib (BAY 73-4506) is an oral multikinase inhibitor of a broad range of angiogenic, oncogenic, and stromal kinases. The phase III CORRECT trial was conducted to evaluate efficacy and safety of regorafenib in pts with mCRC who had progressed after all approved standard therapies. Methods: Enrollment criteria included documented mCRC and progression during or ≤3 months after last standard therapy. Pts were randomized 2:1 to receive regorafenib (160 mg od po, 3 weeks on/1 week off) plus BSC, or placebo (PL) plus BSC. Pts continued on treatment until progression, death, or unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), safety, and quality of life. Results: From May 2010 to March 2011, 760 pts were randomized (regorafenib: 505; PL: 255). Baseline characteristics were balanced between two arms. Preliminary results are available from a pre-planned formal interim analysis. The estimated hazard ratio (HR) for OS was 0.773 (95% CI: 0.635, 0.941; 1-sided p=0.0051). Median OS was 6.4 mos (95% CI: 5.9, 7.3) for regorafenib and 5.0 mos (95% CI: 4.4, 5.8) for PL. The estimated HR for PFS was 0.493 (95% CI: 0.418, 0.581; 1-sided p < 0.000001). Median PFS was 1.9 mos (95% CI: 1.88, 2.17) for regorafenib and 1.7 mos (95% CI: 1.68, 1.74) for PL. ORR was 1.6% for regorafenib and 0.4% for PL. DCR was 44% for regorafenib and 15% for PL (p < 0.000001). Since the prespecified OS efficacy boundary was crossed (nominal α: 0.0093), the Data Monitoring Committee recommended to unblind the study and pts on PL were allowed to cross over to regorafenib. The most frequent grade 3+ AEs in the regorafenib arm were hand-foot skin reaction (17%), fatigue (15%), diarrhea (8%), hyperbilirubinemia (8%), and hypertension (7%). Updated results will be presented. Conclusions: Statistically significant benefit in OS and PFS was observed for regorafenib over PL in pts with mCRC who have failed all approved standard therapies. No new or unexpected safety signal was found.

Purpose Trastuzumab and pertuzumab are human epidermal growth factor receptor 2 (HER2) –targeted monoclonal antibodies, and trastuzumab emtansine (T-DM1) is an antibody–drug conjugate that combines the properties of trastuzumab with the cytotoxic activity of DM1. T-DM1 demonstrated encouraging efficacy and safety in a phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Combination T-DM1 and pertuzumab showed synergistic activity in cell culture models and had an acceptable safety profile in a phase Ib and II study. Methods In the MARIANNE study, 1,095 patients with centrally assessed, HER2-positive, advanced breast cancer and no prior therapy for advanced disease were randomly assigned 1:1:1 to control (trastuzumab plus taxane), T-DM1 plus placebo, hereafter T-DM1, or T-DM1 plus pertuzumab at standard doses. Primary end point was progression-free survival (PFS), as assessed by independent review. Results T-DM1 and T-DM1 plus pertuzumab showed noninferior PFS compared with trastuzumab plus taxane (median PFS: 13.7 months with trastuzumab plus taxane, 14.1 months with T-DM1, and 15.2 months with T-DM1 plus pertuzumab). Neither experimental arm showed PFS superiority to trastuzumab plus taxane. Response rate was 67.9% in patients who were treated with trastuzumab plus taxane, 59.7% with T-DM1, and 64.2% with T-DM1 plus pertuzumab; median response duration was 12.5 months, 20.7 months, and 21.2 months, respectively. The incidence of grade ≥ 3 adverse events was numerically higher in the control arm (54.1%) versus the T-DM1 arm (45.4%) and T-DM1 plus pertuzumab arm (46.2%). Numerically fewer patients discontinued treatment because of adverse events in the T-DM1 arms, and health-related quality of life was maintained for longer in the T-DM1 arms. Conclusion T-DM1 showed noninferior, but not superior, efficacy and better tolerability than did taxane plus trastuzumab for first-line treatment of HER2-positive, advanced breast cancer.

Background: Left ventricular systolic dysfunction (LVSD) and LV diastolic dysfunction (LVDD) are commonly seen in severe sepsis and septic shock; however, their role in patients with concurrent invasive mechanical ventilation (IMV) is less well defined. Methods: This was a prospective observational study on all patients admitted to all the intensive care units (ICUs) at Mayo Clinic, Rochester from August 2007 to January 2009. All adult patients with severe sepsis and septic shock and concurrent IMV without prior heart failure underwent transthoracic echocardiography within 24 hours. Patients with active pregnancy, prior congenital or valvular heart disease, and prosthetic cardiac valves were excluded. Left ventricular systolic dysfunction was defined as LV ejection fraction (LVEF) <50% and LVDD as E/e′ >15. Primary outcome was hospital mortality, and secondary outcomes included IMV duration, ICU length of stay (LOS), and total LOS. Two-tailed P value of <.05 was considered statistically significant. Results: In a total of 106 patients, 58 (54.7%) met our inclusion criteria, with 17 (29.3%), 11 (19.0%), and 5 (8.6%) having LVSD, LVDD, and both, respectively. The cohorts with and without LVSD and LVDD did not differ significantly in their baseline characteristics and laboratory and ventilatory parameters. Compared to those without LVSD, patients with LVSD had higher LV end-systolic diameters but were not different in their left atrial diameters or E/e′ ratio. Patients with LVDD had a higher E velocity and E/e′ ratio compared to those without LVDD. Hospital mortality was not different in patients with and without LVSD (8 [47%] vs 21 [51%], P = 1.00) and LVDD (8 [73%] vs 21 [45%], P = .18). Secondary outcomes were not different between the 2 groups. Conclusion: Left ventricular systolic or diastolic dysfunction did not influence in-hospital outcomes in patients with severe sepsis and septic shock and concurrent IMV.

Background: One factor believed to contribute to the development of hallux valgus is an abnormality in collagen structure and makeup of the medial collateral ligament (MCL) of the first metatarsophalangeal joint (MTPJ). We hypothesized that the mechanical properties of the MCL in feet with hallux valgus are significantly different from those in normal feet and that these differences may be related to alterations in the type or distribution of collagen fibers at the interface between the MCL and the bone. Materials and Methods: Seven normal fresh-frozen cadaver feet were compared to four cadaver feet that had hallux valgus deformities. The MCL mechanical properties, structure of collagen fibers, and content proportion of type I and type III collagen were determined. Results: The load-deformation and stress-strain curves were curvilinear with three regions: laxity, toe, and linear regions. Laxity of the MCL in feet with hallux valgus was significantly larger than that of normal feet ( p = 0.022). Stiffness and tensile modulus in the toe region in feet with hallux valgus were significantly smaller than those in normal feet ( p = 0.004); however, stiffness and tensile modulus in the linear region were not significantly different. The MCL collagen fibrils in the feet with hallux valgus had a more wavy distribution than the fibrils in the normal feet. Conclusions: In general, strong staining for collagen III and to a lesser extent, collagen I was observed at the interface between the MCL and bone in the feet with hallux valgus but not in the normal feet. These results indicate that the abnormal mechanical properties of the MCL in feet with hallux valgus may be related to differences in the organization of collagen I and collagen III fibrils.

Raghib defect and double-orifice tricuspid valve are two rare congenital heart defects. We report a case of a 42-year-old man with both Raghib defect and DOTV. The patient underwent reroofing of the coronary sinus with an intra-atrial baffle and annuloplasty of the tricuspid and mitral valves via median sternotomy.

Objectives: Vascular endothelial growth factor overexpression, seen in 42% to 76% of biliary tract cancers (BTCs), correlates with poor survival. We explored the safety/efficacy and potential biomarkers for bevacizumab in combination with gemcitabine-capecitabine in advanced BTCs. Patients and Methods: Inoperable stage III/IV BTC patients in our prospective study were given 1000 mg/m 2 of gemcitabine (on days 1, 8), 650 mg/m 2 of capecitabine (on days 1 to 14), and 15 mg/kg of bevacizumab (on day 1) in 21-day cycles. Circulating tumor cells and quality of life were assessed at baseline and before cycle 2 and 3. Results: In total, 50 patients with gallbladder cancer (22%), intrahepatic (58%), and extrahepatic (20%) cholangiocarcinoma, received a median of 8 treatment cycles for median treatment duration of 5.8 months. Common grade 3/4 toxicities were neutropenia (36%), thrombocytopenia (16%), fatigue (20%), infections (14%), and hand-foot syndrome (10%). There were 12 partial response (24%), 24 stable disease (48%) with clinical benefit rate of 72%. Median progression-free survival was 8.1 months (95% confidence interval, 5.3-9.9). Median overall survival was 10.2 months (95% confidence interval, 7.5-13.7). Circulating tumor cells were identified at baseline in 21/46 patients (46%), who had lower median overall survival compared with those without (9.4 vs. 13.7 mo; P =0.29). Patients with quality of life scores greater than the group median by the end of first cycle of treatment had improved survival compared with those who did not (13.3 vs. 9.4 mo; P =0.39). Conclusions: Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.