Recent Publications by CFE Educators

PURPOSE

To perform a systematic review and pooled meta-analysis of adrenal metastasis stereotactic body radiation therapy (SBRT) outcomes, treatment characteristics, and toxicity to define the efficacy and propose guidelines for intervention.

METHODS AND MATERIALS

We performed a comprehensive literature search of the Embase and PubMed databases of studies reporting outcome or toxicity data for photon-based SBRT of adrenal metastases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We then conducted a meta-analysis to estimate pooled overall response, local control (LC), and overall survival and analyzed these outcomes in the context of dosimetric parameters and toxicity using metaregression.

RESULTS

Thirty-nine studies published between 2009 and 2019 reporting outcomes on 1006 patients were included. The median follow-up was 12 months, and the median biological equivalent dose (BED10, alpha/beta = 10) was 67 Gy. The pooled overall response was 54.6% (95% confidence interval [CI], 46.5%-62.5%). The pooled 1- and 2-year rates of LC were 82% (95% CI, 74%-88%) and 63% (95% CI, 50%-74%), respectively, and the pooled 1- and 2-year overall survival rates were 66% (95% CI, 57%-74%) and 42% (95% CI, 31%-53%), respectively. There was a strong positive association between SBRT dose and 1- and 2-year LC (P .0001, P = .0002) and an association with 2-year OS (P = .03). Based on a metaregression of dose and LC, BED10 of 60 Gy, 80 Gy, and 100 Gy predicted 1-year LC of 70.5%, 84.8%, and 92.9% and 2-year LC of 47.8%, 70.1%, and 85.6%, respectively. The overall rate of grade 3 or higher toxicity was 1.8%.

CONCLUSIONS

SBRT of adrenal metastases provides good 1-year LC with an excellent safety profile, and dose escalation may be associated with improved LC. Prospective studies are needed to validate these findings and determine whether there are subsets of patients for whom adrenal metastasis-directed SBRT may confer a survival advantage.

Deciding on specific treatment strategies involves not only tumor stage, performance status, and severity of underlying liver disease, but additional factors such as biomarkers, organ availability, and radiographic tumor response to treatment. In this review, we present hepatocellular carcinoma (HCC) cases to highlight how to determine therapeutic options for HCC in specific scenarios, including resection versus liver transplant, choice of initial local regional treatment, tumor downstaging, and systemic therapies for advanced HCC.

The illness started with pain and stiffness in her bilateral hands and wrists four months prior, with progression to bilateral elbows, knees, and ankles. The pain and stiffness were worse in the morning and limited her ability to use her hands or walk comfortably. She also noted swelling of her hands, knees, and ankles. The pain and swelling improved slightly with ibuprofen. She also noted increased fatigue, alopecia, decreased appetite, and nausea. She went to urgent care one month earlier and a physician prescribed ibuprofen and obtained initial serologies.

PURPOSE

Risk factors for complications after artificial urinary sphincter surgery include a history of pelvic radiation and prior artificial urinary sphincter complication. The survival of a second artificial urinary sphincter in the setting of prior device complication and radiation is not well described. We report the survival of redo artificial urinary sphincter surgery and identify risk factors for repeat complications.

MATERIALS AND METHODS

A multi-institutional database was queried for redo artificial urinary sphincter surgeries. The primary outcome was median survival of a second and third artificial urinary sphincter in radiated and nonradiated cases. A Cox proportional hazards survival analysis was performed to identify additional patient and surgery risk factors.

RESULTS

Median time to explantation of the initial artificial urinary sphincter in radiated (150) and nonradiated (174) cases was 26.4 and 35.6 months, respectively (p=0.043). For a second device median time to explantation was 30.1 and 38.7 months (p=0.034) and for a third device it was 28.5 and 30.6 months (p=0.020), respectively. The 5-year revision-free survival for patients undergoing a second artificial urinary sphincter surgery with no risk factors, history of radiation, history of urethroplasty, and history of radiation and urethroplasty were 83.1%, 72.6%, 63.9% and 46%, respectively.

CONCLUSIONS

Patients without additional risk factors undergoing second and third artificial urinary sphincter surgeries experience revision-free rates similar to those of their initial artificial urinary sphincter devices. Patients who have been treated with pelvic radiation have earlier artificial urinary sphincter complications. When multiple risk factors exist, revision-free rates decrease significantly.

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and samples. To address this challenge, we conducted a comprehensive meta-analysis of fMRI studies of stimulus-induced pain in healthy participants. Following pre-registration, two independent reviewers evaluated 4,927 abstracts returned from a search of 8 databases, with 222 fMRI experiments meeting inclusion criteria. We analyzed these experiments using Activation Likelihood Estimation with rigorous type I error control (voxel height p 0.001, cluster p 0.05 FWE-corrected) and found a convergent, largely bilateral pattern of pain-related activation in the secondary somatosensory cortex, insula, midcingulate cortex, and thalamus. Notably, these regions were consistently recruited regardless of stimulation technique, location of induction, and participant sex. These findings suggest a highly-conserved core set of pain-related brain areas, encouraging applications as a biomarker for novel therapeutics targeting acute nociceptive pain.

Aspiring medical educators and their advisors often lack clarity about career paths. To provide guidance to faculty pursuing careers as educators, we sought to explore perceived factors that contributed to the career development of outstanding medical educators. Using a thematic analysis, investigators at two institutions interviewed 39 full or associate professor physician faculty with prominent roles as medical educators in 2016. The social cognitive career theory (SCCT) informed the interview guide. Investigators developed the codebook and performed iterative analysis using qualitative methods. Extensive team discussion generated the final themes. Eight themes emerged related to preparation, early successes, mentors, networks, faculty development, balance, work environment, and multiple identities. Preparation led to early successes, which served as "launch points," while mentors, networks, and faculty development programs served as career accelerators to open more opportunities, and a supportive work environment was an additional enabler of this pathway. Educators who reported balance between work and outside interests described boundary setting as well as selectively choosing new opportunities to establish boundaries in mid-career. Participants described multiple professional identities, and clinician and educator identities tended to merge and reinforce each other as careers progressed. This study revealed common themes describing trajectories of success among medical educators. These themes aligned with the SCCT, and typically replayed and spiraled over the course of the educators' careers. These findings resonate with other studies, lending credence to an approach to career development that can be shared with junior faculty who are exploring careers in medical education.

OBJECTIVE

To estimate healthcare expenditures that could be impacted by advanced diagnostic testing for patients hospitalized with meningitis or encephalitis.

METHODS

Patients hospitalized with meningitis (N = 23,933) or encephalitis (N = 7,858) in the U.S. were identified in the 2010-2014 Truven Health MarketScan Commercial Claims and Encounters Database using ICD-9-CM diagnostic codes. The database included an average of 40.8 million commercially insured enrollees under age 65 per year. Clinical, demographic and healthcare utilization criteria were used to identify patient subgroups early in their episode who were at risk to have high inpatient expenditures. Healthcare expenditures of patients within each subgroup were bifurcated: those expenditures that remained five days after the patient could be classified into the subgroup versus those that had occurred previously.

RESULTS

The hospitalization episode rate per 100,000 enrollee-years for meningitis was 13.0 (95% CI: 12.9-13.2) and for encephalitis was 4.3 (95% CI: 4.2-4.4), with mean inpatient expenditures of $36,891 (SD = $92,636) and $60,181 (SD = $130,276), respectively. If advanced diagnostic testing had been administered on the day that a patient could be classified into a subgroup, then a test with a five-day turnaround time could impact the following mean inpatient expenditures that remained by subgroup for patients with meningitis or encephalitis, respectively: had a neurosurgical procedure ($83,337 and $56,020), had an ICU stay ($34,221 and $46,051), had HIV-1 infection or a previous organ transplant ($37,702 and $62,222), were age 1 year ($35,371 and $52,812), or had a hospital length of stay >2 days ($18,325 and $30,244).

DISCUSSION

Inpatient expenditures for patients hospitalized with meningitis or encephalitis were substantial and varied widely. Patient subgroups who had high healthcare expenditures could be identified early in their stay, raising the potential for advanced diagnostic testing to lower these expenditures.

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management.