Recent Publications by CFE Educators

A variety of cardiovascular clinical manifestations have been described in patients with spondyloarthritis, especially in well-established ankylosing spondylitis. These include both structural heart disease, conduction defects and ischemic heart disease. The true prevalence of cardiovascular involvement in patients with axial spondyloarthritis, including non-radiographic disease needs to be further defined.

PURPOSE

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and is often resistant to conventional therapies. The MYC oncogene is commonly overexpressed in AML but has remained an elusive target. We aimed to examine the consequences of targeting MYC both directly and indirectly in AML overexpressing MYC/Myc due to trisomy 8/15 (human/mouse), FLT3-ITD mutation, or gene amplification.

METHODS

We performed in vivo knockdown of Myc (shRNAs) and both in vitro and in vivo experiments using four drugs with indirect anti-MYC activity: VX-680, GDC-0941, artemisinin, and JQ1.

RESULTS

shRNA knockdown of Myc in mice prolonged survival, regardless of the mechanism underlying MYC overexpression. VX-680, an aurora kinase inhibitor, demonstrated in vitro efficacy against human MYC-overexpressing AMLs regardless of the mechanism of MYC overexpression, but was weakest against a MYC-amplified cell line. GDC-0941, a PI3-kinase inhibitor, demonstrated efficacy against several MYC-overexpressing AMLs, although only in vitro. Artemisinin, an antimalarial, did not demonstrate consistent efficacy against any of the human AMLs tested. JQ1, a bromodomain and extra-terminal bromodomain inhibitor, demonstrated both in vitro and in vivo efficacy against several MYC-overexpressing AMLs. We also confirmed a decrease in MYC levels at growth inhibitory doses for JQ1, and importantly, sensitivity of AML cell lines to JQ1 appeared independent of the mechanism of MYC overexpression.

CONCLUSIONS

Our data support growing evidence that JQ1 and related compounds may have clinical efficacy in AML treatment regardless of the genetic abnormalities underlying MYC deregulation.

In the setting of end-stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end-stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.

PURPOSE

The purpose of this study was to evaluate workflow and patient outcomes related to frameless stereotactic radiation surgery (SRS) for brain metastases.

METHODS AND MATERIALS

We reviewed all treatment demographics, clinical outcomes, and workflow timing, including time from magnetic resonance imaging (MRI), computed tomography (CT) simulation, insurance authorization, and consultation to the start of SRS for brain metastases.

RESULTS

A total of 82 patients with 151 brain metastases treated with SRS were evaluated. The median times from consultation, insurance authorization, CT simulation, and MRI for treatment planning were 15, 7, 6, and 11 days to SRS. Local freedom from progression (LFFP) was lower in metastases with MRI ≥ 14 days before treatment (P = .0003, log rank). The 6- and 12-month LFFP rate were 95% and 75% for metastasis with interval of 14 days from MRI to treatment compared to 56% and 34% for metastases with MRI ≥ 14 days before treatment. On multivariate analysis, LFFP remained significantly lower for lesions with MRI ≥ 14 days at SRS (P = .002, Cox proportional hazards; hazard ratio: 3.4, 95% confidence interval: 1.6-7.3).

CONCLUSIONS

Delay from MRI to SRS treatment delivery for brain metastases appears to reduce local control. Future studies should monitor the timing from imaging acquisition to treatment delivery. Our experience suggests that the time from MRI to treatment should be 14 days.

The present study evaluated the frequency of periprosthetic fractures and tested the hypothesis that this population's demographics and outcomes are unique as compared with other arthroplasty patients. The National Hospital Discharge Survey provided the raw data. Individuals admitted with a primary TKA, primary THA, or revision TJA were selected. Annual rates were then calculated and demographics and outcomes compared. 30,624 patients were reviewed. The proportion of admissions for periprosthetic fractures ranged from 4.2% to 7.4% annually. As compared to patients admitted for other TJA diagnoses, individuals admitted with periprosthetic fracture were older, were more often female, were more often admitted emergently/urgently, had longer lengths of stay, had higher rates of discharge to places other than home, and had a significantly elevated mortality.

BACKGROUND

The protective effect of colonoscopy against proximal colorectal cancer is variable and depends on the detection and complete removal of precancerous polyps.

OBJECTIVE

To estimate the efficacy of colonoscopy in a medical center with open-access screening colonoscopy since 1998.

DESIGN

Nested case-control study with incidence density sampling.

SETTING

University-affiliated Veterans Affairs Medical Center.

PATIENTS

Colorectal cancer (CRC) cases and control subjects selected from screening age patients matched by age, gender, and date of first primary care visit.

MAIN OUTCOME MEASUREMENT

Colonoscopy preceding the CRC diagnosis date.

RESULTS

A total of 20.2% of CRC cases had a colonoscopy in the preceding 10 years compared with 49.0% of control subjects (adjusted odds ratio [aOR], 0.20; 95% confidence interval [CI], 0.11-0.34). Colonoscopy was strongly associated with decreased odds of both distal CRC (aOR, 0.16; 95% CI, 0.07-0.34) and proximal CRC (aOR, 0.26; 95% CI, 0.11-0.58). The fraction of cases attributed to interval cancers was 10.5%. Missed lesions predominantly localized to the cecum and rectum, and recurrent lesions clustered in the hepatic flexure. Cecal intubation rate was 93% (98% in adequately prepped patients), and the adenoma detection rate was 45.2% in the control group.

LIMITATIONS

Single-center, retrospective case-control design.

CONCLUSION

In an open access colonoscopy program characterized by a high cecal intubation rate and adenoma detection rate, colonoscopy was strongly associated with reduced odds of both distal and proximal CRC. Among interval cancers, missed lesions clustered in the cecum and rectum and recurrent lesions in the hepatic flexure.