The reticulospinal tract was recently shown to have synaptic connections to the intrinsic muscles of the fingers in nonhuman primates, indicating it may contribute to hand function long thought to be controlled exclusively through corticospinal pathways. Our objective was to obtain evidence supporting the hypothesis that these same anatomical connections exist in humans. startReact, an involuntary release of a planned movement via the startle reflex, provides a noninvasive means to examine the reticulospinal tract in humans. We found that startReact was triggered during coordinated grasp but not individuated finger movements. This result suggests that the reticulospinal tract does have connections to the intrinsic muscles of the fingers in humans but its functional role is limited to coordinated movement of the whole hand. These results do not diminish the well-established role of corticospinal pathways in the control of hand movement. Indeed, they cement the significance of corticospinal pathways in individuated finger movement control. Still, these results point to an updated and expanded view of distal hand control where reticulospinal and corticospinal pathways work in parallel to generate a large repertoire of diverse, coordinated movement in the hand. Finally, the presence of reticulospinal pathways to the muscles of the hand makes this pathway an attractive therapeutic target for clinical populations where the corticospinal tract is absent or injured.

Emerging reports on human islets emphasize distinct differences from the widely accepted prototype of rodent islets, raising questions over their suitability for human studies. Here we aim at elucidating architectural differences and similarities of human versus rodent islets. The cellular composition and architecture of human and rodent islets were compared through three-dimensional (3D) reconstructions. Physiological and pathological changes were examined using islets from various mouse models such as non-obese diabetic (NOD), ob/ob, db/db mice and during pregnancy. A subpopulation of human islets is composed of clusters of alpha-cells within the central beta-cell cores, while the overall proportion of alpha-cells varies among islets. In mouse islets under normal conditions, alpha-cells are localized in the islet periphery, but they do not envelop the entire betacell core, so that beta-cells are exposed on the outer layer of the islet, as in most human islets. Also, an increased proportion of alpha-cells within the central core is observed in the pancreas of mouse models exhibiting increased demand for insulin. In summary, human and mouse islets share common architectural features as endocrine micro-organs. Since these may hold a key to better understanding islet plasticity, our concept of the prototypic islet should be revised.

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Asymptomatic kidney transplant candidates with ≥3 AHA/ACCF risk factors are at increased cardiac risk, and should be considered for noninvasive CAD surveillance. Intermediate risk patients (3-4 factors) benefit the most from pre-transplant MPI to define long-term MACE risk.

Background: Thoracic irradiation (TIR) is associated with an increased risk of coronary artery disease (CAD) and coronary-related death. Lung cancer patients receive considerable doses of TIR, making them a high-risk population that may benefit from post-therapy surveillance. Coronary artery calcium (CAC) is a known biomarker of CAD development and may serve as a useful indicator of disease progression in this population. We hypothesized greater CAC progression in lung cancer patients subjected to higher whole heart radiation doses. Methods: CAC progression (pre-and >2 years post-TIR) from chest CT scans of lung cancer patients were evaluated. A 2:1 matched control population was established controlling for age, gender, race, and CT scan interval. Vessel-specific CAC presence, progression, and extension in pre-and post-interval CT studies was evaluated by two blinded reviewers using the ordinal method. Dosimetric treatment files were restored and contours of the whole heart and proximal left anterior descending artery (LAD) were created within existing plans to compute radiation doses (Pinnacle Treatment Planning Software). Binary logistic regression analysis identified factors predictive for CAC development. Multiple logistic regression analysis with hierarchal method was used to assess covariates. Results: Thirty-five patients and 65 controls (50% female) were evaluated; mean age 57 years, mean follow-up post-radiation 4.9±2.2 years. Average mean and maximum left anterior descending coronary artery (LAD) radiation doses were 19.9 Gy (95% CI, 14.1-25.7) and 30.7 Gy (95% CI, 23.8-37.5), respectively; 91.6% inter-observer variability. There was greater incidence of coronary calcification in irradiated patients (48.6% vs. 24.6%; P=0.01). In interval CT scans, a greater proportion of radiated patients demonstrated new coronary calcification (P=0.007) and extension within the LAD (P=0.003). Radiation exposure was the only independent predictor of new calcification (OR 3.1; 95% CI: 1.09-9.2). Conclusions:We identified both an increase in the development and progression of CAC in lung cancer patients receiving TIR. Future studies utilizing alternative cancer populations and larger sample sizes are necessary to further correlate radiographic and dosimetric observations to cardiovascular events.

Purpose/ObjectivesTo establish the feasibility and safety of intraoperative placement of cesium-131 (Cs-131) seeds for re-irradiation in recurrent head and neck cancer (HNC).MethodsPatients with resectable recurrent HNC who were deemed to have a high risk of second recurrence were eligible. Immediately after tumor extirpation, seeds were implanted in the surgical bed based on the preoperative treatment plan with intraoperative adjustment. The surgical bed and the seeds were covered with a regional flap or microvascular free flap. A CT of the neck was obtained on postoperative day 1 for evaluation of the postoperative dose distribution. Patients were followed 1 and 3 months after surgery, then every 3 months in the first 2 years.ResultsFrom November 2016 to September 2018, 15 patients were recruited and 12 patients received treatment per protocol. For the patients who had implants, the sites of initial recurrence included 10 neck alone, 1 neck and larynx, and 1 neck/peristomal. The median follow-up was 21.4 months. After surgery, patients remained hospitalized for a median of 6 days. There were no high-grade toxicities except two patients with wound complications requiring wound care. Eight patients had recurrences, three locoregional alone, three distant alone, and two with both locoregional and distant recurrences. Only one patient had an in-field failure. Five patients died, with 1- and 2-year overall survival of 75 and 58%.ConclusionsCs-131 implant after surgical resection in recurrent HNC is feasible and safe. There were no unexpected severe toxicities. Most failures were out-of-field or distant.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02794675.

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e12547 Background: Clinical trials have demonstrated radiation therapy (RT) significantly reduces local recurrence following BCS, but that omission of RT does not compromise survival in the majority of women with early stage, low risk breast cancer. Criteria for omission of RT have been based on clinical factors such as age, stage, tumor size, surgical margins and estrogen receptor (ER) status. The utility of Oncotype DX RS in determining benefit of RT is not well defined. Methods: The National Cancer Database (NCDB) was queried for women ages 50-69 with T1N0M0, grade 1-2, ER+, Her2- breast cancer who underwent BCS with negative margins and had Oncotype DX RS of 0-18. Overall survival (OS) was estimated using the Kaplan-Meier method and compared between patients who received RT and endocrine therapy (ET) versus ET alone using logrank analysis. Propensity matching was performed to reduce the impact of potential confounders and balance sample bias. Cox proportional hazards regression was used to identify predictors of OS. Results: A total of 13,648 women met inclusion criteria. The median age was 60 years. 13,389 women had adjuvant RT+ET, while 259 women had ET alone. Five year OS was 98.6% in patients who underwent RT+ET compared to 95.5% in those that had ET alone (p = 0.0012). Propensity-matching by age, Charlson Deyo Comorbid Condition score, tumor size, Oncotype RS, and race. Five year OS in the propensity matched cohort was 99.6% for women receiving RT+ET, and 98.3% for ET alone, which was not significantly different (p = 0.095). On multivariate analysis receipt of radiotherapy was not predictive of survival. Age and comorbidity score were the only significant predictors of survival. Conclusions: Patients who receive adjuvant RT with low risk, early stage ER+/Her2- breast cancer had higher OS than women who received ET alone on univariate analysis. However, results from both multivariate analysis and propensity score matching suggest no survival benefit to the addition of RT. Prospective studies are underway assessing omission of RT on the basis of multigene assays rather than clinical features alone. [Table: see text]