Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations

Background

Major guidelines do not recommend routine molecular profiling of lung squamous-cell carcinoma (LUSC) because the prevalence of actionable alterations is thought to be low. Increased utilization of next-generation sequencing (NGS), particularly with cell-free circulating tumor DNA, facilitates reevaluation of this premise.

Two-year outcome of patients treated with sirolimus- versus paclitaxel-eluting stents in an unselected population with coronary artery disease (from the REWARDS Registry)

Multiple studies comparing sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with coronary artery disease have been performed. Despite these comparisons, it remains uncertain whether a differential in long-term efficacy and safety exists. Unselected patients treated exclusively with 1 drug-eluting stent type were enrolled in the Registry Experience at the Washington Hospital Center with Drug-Eluting Stents. There were 2,099 patients (3,766 lesions) treated with SES and 1,079 patients (1,850 lesions) treated with PES. Patients were followed at 30 days, 1 year, and 2 years for the clinical endpoints of death, myocardial infarction, target vessel revascularization, and definite and definite/probable stent thrombosis. Patients in the SES group had more dyslipidemia, history of congestive heart failure, and ostial lesions; patients treated with PES had more previous coronary artery bypass surgery, unstable angina, and type C lesions. At 2 years, unadjusted major adverse cardiac events (MACE) (22.6% vs 21.1%, p = 0.3) and target vessel revascularization (13.3% vs 11.2%, p = 0.1) were comparable. The incidence of definite stent thrombosis was higher in the SES group (1.8% vs 0.9%, p = 0.05) driven by early events. Similar results were seen after adjustment for baseline differences: MACE (hazard ratio 1.1, 95% confidence interval [CI] 0.9 to 1.3, p = 0.5), definite stent thrombosis (hazard ratio 2.3, 95% CI 1.0 to 5.2, p = 0.05), and target vessel revascularization (hazard ratio 1.1, 95% CI 0.9 to 1.4, p = 0.4). The incidence and rate of late stent thrombosis (>30 days) were similar (0.7% vs 0.5%, p = 0.4 and 0.24%/year, both groups, respectively). In conclusion, no major differential in long-term safety or efficacy was detected between SES and PES; both stent types were efficacious in reducing revascularization but were limited by a small continual increase in late stent thrombosis.     

Identifying predictors of treatment outcome in a drug court program

Drug courts are popular for dealing with drug-abusing offenders. However, relatively little is known about participant characteristics that reliably predict either success or failure in these treatment settings. In this article, we report on 99 individuals who were enrolled in a drug court program (approximately one-half of whom successfully completed the program). Using, logistic regression techniques we identified 2 significant predictors of outcome. First, individuals who were employed at the time of their enrollment into the drug court program were more likely to successfully complete the treatment program. Second, individuals with a history of illicit intravenous drug use were less likely to complete the program.     

Quality of life in bridge-to-transplant patients with chronic heart failure after implantation of an axial flow ventricular assist device

Research suggests that ventricular assist devices improve quality of life for congestive heart failure patients awaiting heart transplantation. Axial flow ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) represent the newest type of ventricular assist device technology, but their effects on quality of life are not well understood. Therefore, the authors administered the Minnesota Living with Heart Failure Questionnaire to patients who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients completed the Minnesota Living with Heart Failure Questionnaire immediately before device implantation, 1 month after implantation, immediately before heart transplantation, and 1 month after transplantation. One month after implantation of the device, the nine patients who completed the study showed significant improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008) quality of life. These improvements were maintained until the device was explanted. The authors conclude that implantation of the Jarvik 2000 ventricular assist device can substantially improve quality of life for patients awaiting heart transplantation.     

Bleeding risk and outcomes of Bivalirudin versus Glycoprotein IIb/IIIa inhibitors with targeted low-dose unfractionated Heparin in patients having percutaneous coronary intervention for either stable or unstable angina pectoris

For patients undergoing elective percutaneous coronary intervention (PCI), procedural anticoagulation with bivalirudin was previously shown to significantly reduce bleeding complications at the cost of a modest increase in ischemic events compared with unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitors (GPIs). However, the excess bleeding in patients treated with UFH and GPIs may have been caused by excessively high UFH doses and increased activated clotting times. This study sought to determine the bleeding risk of targeted low-dose UFH with GPIs compared with bivalirudin in patients undergoing elective PCI. Of 1,205 patients undergoing elective PCI, 602 underwent PCI with adjunctive UFH and GPIs with the UFH dose targeted to an activated clotting time of approximately 250 seconds, and 603 patients matched for baseline characteristics underwent PCI with bivalirudin. Outcomes were analyzed for major bleeding (hematocrit decrease >15%, gastrointestinal bleed, or major hematoma) and 6-month major adverse cardiac events (death, myocardial infarction, and target-lesion revascularization). The maximum activated clotting time achieved was 261.7 +/- 61.6 seconds in the UFH/GPI group and 355.4 +/- 66.6 in the bivalirudin group (p <0.001). In-hospital major bleeding rates were similar between groups (1.8% UFH/GPI vs 1.7% bivalirudin; p = 0.83), as were transfusion requirements (1.2% UFH/GPI vs 0.5% bivalirudin; p = 0.61). The 6-month major adverse cardiac event rate was also similar between groups (9.5% UFH/GPI vs 9.0% bivalirudin; p = 0.81). In conclusion, there were no significant differences in major bleeding and 6-month major adverse cardiac events for patients undergoing elective PCI treated with targeted low-dose UFH and GPIs compared with those treated with bivalirudin.     

Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes

The purpose of this study was to determine the predictors of lower extremity arterial disease (LEAD) events in a type 1 diabetes population. Data are from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes. At baseline, the study population had a mean age 28 (range, 8 to 47) years and duration 19 (range, 7 to 37) years. LEAD events, assessed by questionnaire or clinical examination, were defined as claudication (Rose questionnaire), foot ulceration, or lower extremity amputation. Estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated from glycosylated hemoglobin (HbA(1)), waist-to-hip ratio (WHR), and hypertension using an equation previously validated with hyperinsulinemic euglycemic clamp studies. There were incident LEAD events in 70 of 586 subjects during 10 years follow-up, giving an incidence density of 1.3 events/100 person-years. Incidence did not differ by gender. Major predictors of LEAD events were diabetes duration, low-density lipoprotein-cholesterol (LDL-C), heart rate, eGDR, log albumin excretion rate (AER), systolic blood pressure (SBP), hypertension, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy (each P <.001). HbA(1), low ankle brachial index (ABI) (<0.9), and a high ankle brachial difference (ABD) (SBP > or = 75 mm Hg) also predicted LEAD events. Cox modeling suggested that duration (P <.001), HbA(1) (P <.001), hypertension (P =.006), log albumin excretion rate (P =.011), and heart rate (P =.028) predicted events independently. The overall model with HbA(1) and hypertension was significantly better than with eGDR, while the alternate models in men were similar. In women, the model with eGDR showed a significantly better fit. Glycemia, insulin resistance, hypertension and renal disease are powerful predictors of symptomatic lower extremity arterial disease in type 1 diabetes.     

Vulnerability to HIV Among Women Formerly Incarcerated and Women with Incarcerated Sexual Partners

HIV risk was assessed in association with a history of incarceration and having a sexual partner with a history of incarceration in a population sample of low-income young women residing in San Francisco. Of the 235 women surveyed, 23% reported prior incarceration and 42% reported having a sexual partner with a history of incarceration. Prevalence of sexually transmitted infections (STIs) (including HIV) was no higher among previously incarcerated women or those with a sexual partner with a history of incarceration. Women with a prior incarceration were significantly more likely to report injecting drugs, exchanging sex for money or drugs, and history of forced sex. Women reporting sexual partners with a history of incarceration were significantly more likely to report incarceration history, history of STIs, and history of forced sex. Interventions aimed at reducing substance abuse, STIs, commercial/survival sex, and the effects of sexual coercion need to be strengthened for women within and transitioning out of correctional facilities.     

Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship Intervention

Purpose of review

Fluoroquinolones are a commonly prescribed antibiotic class that has come under scrutiny in recent years due to mounting evidence of association between adverse drug events, C. difficile infection and isolation of antibiotic-resistant bacteria.

Recent findings

Inpatient antimicrobial stewardship (AMS) programs have a toolbox of potential interventions to curb inappropriate antibiotic use, prevent antibiotic-associated adverse drug events, and avoid unnecessary costs of care. Fluoroquinolone restriction policies in the acute care setting have demonstrated beneficial effects, including decreased rates of C. difficile infection and ESBL-producing Enterobacteriaceae. However, a simple blanket restriction policy may “squeeze the antibiotic balloon” and will likely be insufficient if not implemented in conjunction with other AMS interventions.

Summary

There is a growing body of evidence to support formulary restriction of fluoroquinolones in the acute care setting to decrease rates of C. difficile infection and development of ESBL-producing organisms. Data on how to best implement these restrictions or how to implement outside of acute care settings is limited.