Recent Publications by CFE Educators

Hyperexcitability of the anterior cingulate cortex (ACC) is thought to drive aversion associated with chronic neuropathic pain. Here, we studied the contribution of input from the mediodorsal thalamus (MD) to ACC, using sciatic nerve injury and chemotherapy-induced mouse models of neuropathic pain. Activating MD inputs elicited pain-related aversion in both models. Unexpectedly, excitatory responses of layer V ACC neurons to MD inputs were significantly weaker in pain models compared to controls. This caused the ratio between excitation and feedforward inhibition elicited by MD input to shift toward inhibition, specifically for subcortically projecting (SC) layer V neurons. Furthermore, direct inhibition of SC neurons reproduced the pain-related aversion elicited by activating MD inputs. Finally, both the ability to elicit pain-related aversion and the decrease in excitation were specific to MD inputs; activating basolateral amygdala inputs produced opposite effects. Thus, chronic pain-related aversion may reflect activity changes in specific pathways, rather than generalized ACC hyperactivity.

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Background Current duty hour restrictions have led to increased patient handoffs as well as increased use of faculty in the nocturnist role. Nocturnists typically supervise residents and perform direct patient care leading to a diversity of provider experience level during morning handoffs. In this study, we explored how the presence of nocturnists impacts perceptions patient safety, quality, and educational value of morning care transitions. Methods We performed a cross-sectional survey examining the housestaff and attending perceptions of the morning sign-out of overnight admissions from both night float residents and nocturnists in July of 2016. Survey responses were Likert-style format, querying respondents' level of agreement (1-5, strongly disagree to strongly agree) with statements. 108 providers responded (41% response rate) Results Relative to attendings, residents reported feeling like they had less time to ask questions (4.0 vs. 5.0, 0.001) and felt less comfortable asking questions of the nocturnist during handoff (4.0 vs. 5.0, 0.001). Residents were also less comfortable than attendings in changing a nocturnist's plan of care (4.0 vs. 5.0, 0.001). Housestaff reported that receiving signout from the overnight resident was more likely to improve their confidence managing similar conditions (4.0 vs. 3.0, 0.001). Conclusion The benefits of nocturnist supervision may come at an educational cost as trainees feel less comfortable asking questions or changing the plan of care. With increasingly prevalent night float systems and nocturnist providers, academic programs have to negotiate the balancing safe and high-quality patient care with creating positive learning environments and clear expectations.

PURPOSE

To clinically use the UCSF500, a pancancer, next-generation sequencing assay in uveal melanoma (UM) and to correlate results with gene expression profiling (GEP) and predictive factors for metastasis.

METHODS

Cohort study. Tumor samples of adult UM patients were analyzed with the UCSF500 and GEP. Main outcomes were copy number changes in chromosomes 1, 3, 6, and 8 and mutations in , , , , , , , and . Chromosome 3 loss (a metastasis predictor) was tested for correlation with GEP class, tumor characteristics (largest basal diameter, thickness, ciliary body involvement, and extraocular extension), and histology (presence of epithelioid cells, closed loops, and mitotic count).

RESULTS

The 62 patients had a mean age of 59 years (range, 24-89 years). Chromosome 3 loss was detected in 30 patients and was associated with larger basal tumor diameter (Wilcoxon rank sum test, = 0.015), greater thickness (Wilcoxon rank sum test, = 0.016) and tumor, node, metastasis stage (Fisher test, = 0.006), epithelioid cytology (Fisher test, 0.001), mutation (Fisher test, 0.001), and chromosome 8q gain (Fisher test, 0.001). Class 2 tumors were much more likely to have chromosome 3 loss than class 1 (odds ratio, 121; 0.001). Eleven patients developed metastatic UM, of which five died during the study. All metastatic cases had chromosome 3 loss, 8 gain, mutation, and class 2 GEP. Five class 1 tumors had chromosome 3 loss.

CONCLUSIONS

UCSF500 detects chromosomal copy number changes and missense mutations that correlate strongly with metastasis predictors, including GEP.

TRANSLATIONAL RELEVANCE

Next-generation sequencing of UM should enhance survival prognostication.

BACKGROUND

Single institution reports demonstrate variable safety profiles when liver-directed therapy with Yttrium-90 (Y-90) is followed by hepatectomy. We hypothesized that in well-selected patients, hepatectomy after Y90 is feasible and safe.

METHODS

Nine institutions contributed data for patients undergoing Y90 followed by hepatectomy (2008-2017). Clinicopathologic and perioperative data were analyzed, with 90-day morbidity and mortality as primary endpoints.

RESULTS

Forty-seven patients were included. Median age was 59 (20-75) and 62% were male. Malignancies treated included hepatocellular cancer (n = 14; 30%), colorectal cancer (n = 11; 23%), cholangiocarcinoma (n = 8; 17%), neuroendocrine (n = 8; 17%) and other tumors (n = 6). The distribution of Y-90 treatment was: right (n = 30; 64%), bilobar (n = 14; 30%), and left (n = 3; 6%). Median future liver remnant (FLR) following Y90 was 44% (30-78). Resections were primarily right (n = 16; 34%) and extended right (n = 14; 30%) hepatectomies. The median time to resection from Y90 was 196 days (13-947). The 90-day complication rate was 43% and mortality was 2%. Risk factors for Clavien-Dindo Grade>3 complications included: number of Y-90-treated lobes (OR 4.5; 95% CI1.14-17.7; p = 0.03), extent of surgery (p = 0.04) and operative time (p = 0.009).

CONCLUSIONS

These data demonstrate that hepatectomy following Y-90 is safe in well-selected populations. This multi-disciplinary treatment paradigm should be more widely studied, and potentially adopted, for patients with inadequate FLR.

BACKGROUND

New persistent opioid use has been identified following minor surgical procedures and may contribute to the national opioid epidemic. Prescription patterns vary and we have limited data on patient pain experiences in the outpatient setting. We devised a novel short messaging service survey to record pain scores and opioid use following outpatient thyroid or parathyroid surgery.

MATERIALS AND METHODS

Automated short messaging service was sent daily starting the evening of the operation until postoperative day (POD) 10. Pain was assessed on a 0-10 numeric pain rating scale and opioid use over the prior 24 h was queried.

RESULTS

A total of 1264 survey questions were sent with overall response rate of 84.3%. Fifty-three of 58 patients had a response rate >50% and were included in the final analysis. Average pain score was highest on POD1 at 3.2. Overall, 42.5% of patients utilized opioids on POD0, 55.6% on POD1, and steadily decreased to 7% by POD10. Overall, 34% of patients did not utilize any opioids postoperatively. Scaled total pain scores were higher in patients with thyroid surgery (23.5 versus 12.1, P = 0.02) and lower in those who reported alcohol use (14.9 versus 31.6, P  0.02). Scaled total opioid days were lower in those aged >60 (1.5 versus 3.6, P  0.01) and higher in those with active tobacco use (4.5 versus 2.3, P = 0.04). Pain scores correlated weakly with total opioid days (r = 0.32).

CONCLUSIONS

We demonstrate a novel approach of obtaining patient reported daily, prospective pain scores. This may help us understand patient pain and opioid use in the acute postoperative period especially following outpatient surgery.

Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUV was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUV after endocrine therapy and to consider other tracer uptake metrics with SUV to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted.

CONTEXT

In the clinical environment, health care professionals self-categorise into different groups towards which they develop positive attitudes, whereas they view other groups less favourably. Social identity theory purports that these attitudes influence group processes and may foster conflicts that impede collaborative practice, although this relationship is poorly understood. This study used concepts from social identity theory to examine the interplay between group processes and conflicts, as well as the consequences of these conflicts, with the goal of identifying educational strategies to favour teamwork.

METHODS

Semi-structured interviews with 82 randomly selected physicians and nursing professionals working at a Swiss academic medical centre explored participants' experiences of conflicts. Data analysis was informed by social identity theory and focused on interviews where group processes were highlighted by participants. The analysis sought to uncover how group processes were intertwined with conflicts and how they affected health care professionals.

RESULTS

A total of 42 participants out of the initial pool of 82 interviews shared 52 stories of conflicts involving group processes. Most of these stories were shared by physicians and involved groups of physicians at different hierarchical levels. Conflicts and group processes were linked in two ways: (i) through processes of group membership when individuals struggled to join a relevant group, and (ii) through intergroup boundaries, such as when participants perceived that power differentials disadvantaged their own groups. Conflicts could lead to difficult experiences for clinicians who questioned their abilities, became disillusioned with their professional ideals and developed negative perceptions of other groups.

CONCLUSIONS

This study suggests that conflicts involving group processes may lead to stronger intergroup boundaries, challenging current educational efforts to favour teamwork in health care. Taking steps to create more inclusive groups and to encourage perspective taking may help manage intergroup conflict.