Citations

Abstract Purpose: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses. Experimental Design: Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell–derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates. Results: Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS (P = 0.007) and OS (P = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS (P < 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo. Conclusions: The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.

Background: Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized. Methods: We prospectively recruited residents of Olmsted County, Minnesota, who experienced an event associated with a cardiac troponin T >99th percentile of a normal reference population (≥0.01 ng/mL) between January 1, 2003, and December 31, 2012. Events were retrospectively classified into type 1 myocardial infarction (T1MI, atherothombotic event), T2MI, or myocardial injury (troponin rise not meeting criteria for myocardial infarction [MI]) using the universal definition. Outcomes were long-term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by the inciting event for supply/demand mismatch. Results: A total of 5460 patients had at least one cardiac troponin T ≥0.01 ng/mL; 1365 of these patients were classified as index T1MI (age, 68.5±14.8 years; 63% male) and 1054 were classified as T2MI (age, 73.7±15.8 years; 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100 000 persons between 2003 and 2012 ( P <0.001), whereas the incidence of T2MI declined from 130 to 78 per 100 000 persons ( P =0.02). In comparison with patients with T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and noncardiovascular death. Rates of cardiovascular death were similar after either type of MI (hazard ratio, 0.8 [95% CI, 0.7–1.0], P =0.11). Subclassification of T2MI by cause demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, in comparison with postoperative status, hypotension, anemia, and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI, whereas the occurrence of a new T1MI was relatively rare (estimated rates at 5 years, 9.7% and 1.7%). Conclusions: There has been an evolution in the type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and noncardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design.

Background: The clinical utility of routine electrocardiographic monitoring following percutaneous coronary interventions (PCI) is not well studied. Methods: We prospectively evaluated the incidence, cost, and the clinical implications of actionable arrhythmia alarms on telemetry monitoring following PCI. One thousand three hundred fifty-eight PCI procedures (989 [72.8%] for acute coronary syndrome and 369 [27.2%] for stable angina) on patients admitted to nonintensive care unit were identified and divided into 2 groups; group 1, patients with actionable alarms (AA) and group 2, patients with non-AA. AA included (1) ≥3 s electrical pause or asystole; (2) high-grade Mobitz type II atrioventricular block or complete heart block; (3) ventricular fibrillation; (4) ventricular tachycardia (>15 beats); (5) atrial fibrillation with rapid ventricular response; (6) supraventricular tachycardia (>15 beats). Primary outcomes were 30-day all-cause mortality. Cost-savings analysis was performed. Results: Incidence of AA was 2.2% (37/1672). Time from end of procedure to AA was 5.5 (0.5, 24.5) hours. Patients with AA were older, presented with acute congestive heart failure or non–ST-segment–elevation myocardial infarction, and had multivessel or left main disease. The 30-day all-cause mortality was significantly higher in patients with AA (6.5% versus 0.3% in non-AA [ P <0.001]). Applying the standardized costing approach and tailored monitoring per the American Heart Association guidelines lead to potential cost savings of $622 480.95 for the entire population. Conclusions: AA following PCI were infrequent but were associated with increase in 30-day mortality. Following American Heart Association guidelines for monitoring after PCI can lead to substantial cost saving.

Anomalous coronary artery is an uncommon congenital cardiac anomaly that is often detected incidentally on coronary angiography. It has rarely been reported in the donor heart of patients who have undergone cardiac transplantation. Here, we report a case of a 72-year-old patient who received a second heart transplant and has been identified to have an anomalous left main coronary artery originating from the right coronary sinus on postoperative coronary angiography.

Background: Psychotic symptoms are common in Alzheimer’s disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective: To establish research criteria for the diagnosis of psychosis in AD. Methods: The International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

Despite the current classification of high-grade serous carcinoma (HGSCA) and low-grade serous carcinoma (LGSCA) as mutually exclusive diseases based on morphology and molecular pathogenesis, cases with mixed morphologic features of HGSCA and LGSCA have been reported. Herein we assess the clinicopathologic, immunohistochemical (IHC), and molecular genetic characteristics of a group of these cases, which we termed indeterminate grade serous carcinoma (IGSCA) in comparison with groups of HGSCA and LGSCA. Using the World Health Organization (WHO) classification criteria, we selected 27 LGSCA and 19 IGSCA for detailed morphologic study. Thirteen classic HGSCA, 19 classic LGSCA, and 19 IGSCA were selected for p53 and BRAF V600E IHC and molecular genetic testing by next-generation sequencing. IGSCA showed the architectural patterns of invasion of LGSCA, but with higher grade nuclear features focally and a mitotic index intermediate between LGSCA and HGSCA. Few cases in the IGSCA group showed mutant TP53 by IHC or sequencing (4/18, 22.2%), 1 case had mutant BRAF non-V600E by sequencing, and 1 had an NRAS mutation. When present, the mutations were identical in the low-grade and high-grade areas. The IGSCA group had a long-term survival similar to the classic HGSCA group. IGSCA with mixed morphologic features of HGSCA and LGSCA is a rare and potentially clinically aggressive variant of serous carcinoma. Their distinct morphologic, but heterogenous molecular features, including low frequency of TP53 and BRAF mutations suggest that these rare tumors may have a different pathogenesis pathway compared with classic HGSCA and classic LGSCA.

Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used in acute myocardial infarction (AMI); however, there are limited large-scale national data. Methods: Using the National Inpatient Sample database from 2000 to 2014, a retrospective cohort of AMI utilizing ECMO was identified. Use of percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous left ventricular assist device (LVAD) was also identified in this population. Outcomes of interest included temporal trends in utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD), in-hospital mortality, and resource utilization. Results: In ≈9 million AMI admissions, ECMO was used in 2962 (<0.01%) and implanted a median of 1 day after admission. ECMO was used in 0.5% and 0.3% AMI admissions complicated by cardiogenic shock and cardiac arrest, respectively. ECMO was used more commonly in admissions that were younger, nonwhite, and with less comorbidity. ECMO use was 11× higher in 2014 as compared with 2000 (odds ratio, 11.37 [95% CI, 7.20–17.97]). Same-day percutaneous coronary intervention was performed in 23.1%; intra-aortic balloon pump/percutaneous LVAD was used in 57.9%, of which 30.3% were placed concomitantly. In-hospital mortality with ECMO was 59.2% overall but decreased from 100% (2000) to 45.1% (2014). Durable LVAD and cardiac transplantation were performed in 11.7% as an exit strategy. Of the hospital survivors, 40.8% were discharged to skilled nursing facilities. Older age, male sex, nonwhite race, and lower socioeconomic status were independently associated with higher in-hospital mortality with ECMO use. Conclusions: In AMI admissions, a steady increase was noted in the utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD). In-hospital mortality remained high in AMI admissions treated with ECMO.

AbstractBackgroundThere are limited data on the use of intravascular ultrasound (IVUS), optical coherence tomography (OCT), and fractional flow reserve (FFR) during acute myocardial infarction (AMI).ObjectivesTo assess the temporal trends of IVUS, OCT, and FFR use in AMI.MethodsA retrospective cohort study from the National Inpatient Sample (2004–2014) was designed to include AMI admissions that received coronary angiography. Administrative codes were used to identify percutaneous coronary intervention (PCI), IVUS, OCT, and FFR. Outcomes included temporal trends, inhospital mortality and resource utilization stratified by IVUS, OCT, or FFR use.ResultsIn 4,419,973 AMI admissions, IVUS, OCT, and FFR were used in 2.6%, 0.1%, and 0.6%, respectively. There was a 22‐fold, 118‐fold, and 33‐fold adjusted increase in IVUS, OCT, and FFR use, respectively, in 2014 compared to the first year of use. Non‐ST‐elevation AMI presentation, male sex, private insurance coverage, admission to a large urban hospital, and absence of cardiac arrest and cardiogenic shock were associated with higher IVUS, OCT, or FFR use. PCI was performed in 83.2% of the IVUS, OCT, or FFR cohort compared to 64.2% of the control group (p < .001). The cohort with IVUS/OCT/FFR use had lower inhospital mortality (adjusted odds ratio 0.53 [95% confidence interval 0.50–0.56]), more frequent discharges to home (83.7% vs. 76.8%), shorter hospital stays (4.3 ± 4.4 vs. 5.0 ± 5.5 days) and higher hospitalization costs ($90,683 ± 74,093 vs. $74,671 ± 75,841).ConclusionsIn AMI, the use of IVUS, OCT, and FFR has increased during 2004–2014. Significant patient and hospital‐level disparities exist in the use of these technologies.