Reliability of Intraoperative Testing During Deep Brain Stimulation Surgery.

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for medically refractory Parkinson's disease (PD). During DBS surgery, intraoperative testing is performed to confirm optimal lead placement by determining the stimulation thresholds for symptom improvement and side effects. However, the reliability of intraoperative testing in predicting distant postoperative thresholds is unknown. In this study, we hypothesized that intraoperative testing reliably estimates postoperative thresholds for both symptom improvement and side effects. METHODS: We retrospectively analyzed a prospective database with intraoperative and postoperative thresholds for symptom improvement and side effects from a cohort of 66 PD patients who underwent STN DBS. We recorded the stimulation locations relative to the mid-commissural point. Within-patient stimulation pairs were generated by clustering the intraoperative stimulation locations closest to the DBS contacts. We computed the distance between stimulation locations and atlas-based pyramidal tract (PT) and medial lemniscus (ML) masks. A leave-one-out cross-validation analysis was performed to determine the reliability of intraoperative testing in predicting postoperative thresholds while controlling for the distance from the relevant tracks. RESULTS: Intraoperative testing reliably predicted (area under ROC >0.8) postoperative thresholds for tremor and rigidity improvements, as well as stimulation-induced motor contractions and paresthesias. The reliability was poor for improvement in bradykinesia. CONCLUSION: Intraoperative testing reliably predicts postoperative thresholds. These results are relevant during the informed consent process and patient counseling for DBS surgery. These will also guide the development of future methods for intraoperative feedback, especially during asleep DBS.

Arranging Hospice Care from the Emergency Department: A Single Center Retrospective Study.

BACKGROUND: Arranging hospice services from the Emergency Department (ED) can be difficult due to physician discomfort, time constraints, and the intensity of care coordination needed. We report patient and visit characteristics associated with successful transition from the ED directly to hospice. METHODS: Setting: Academic ED with 82,000 annual visits. POPULATION: ED patients with a referral to hospice order placed during the ED visit from January 2014-December 2018. Charts were abstracted by trained, non-blinded personnel. Primary goal was to evaluate patient and visit factors associated with requiring admission for hospice transition. RESULTS: Electronic Health Record inquiry yielded 113 patients, 93 of which met inclusion criteria. Patients were aged 65.8 years (range 32-92), 54% were female, and 78% were white, non-hispanic. The majority had cancer (78%, n = d72) and were on public insurance (60%, n = 56). Half (55%, n = 51) were full code upon arrival. Average ED length of stay was 4.6 ± 2.6 hours. Discharge from the ED to hospice was successful for 38% (n = 35), a few (n = 5) were dispositioned to an ED observation unit, and 57% (n = 53) were admitted. Only 10 (11%) required an inpatient length of stay longer than an observation visit (2 days). Case management and social work team arranged for transportation (54.8%, n = 51), hospital beds (16.1%, n = 16), respiratory equipment (18.3%, n = 17), facility placement (33.3%, n = 31), and home health aides (29.0%, n = 27). CONCLUSION: Transitioning patients to hospice care from the ED is possible within a typical ED length of stay with assistance from a case manager/social work team.

Distinct macrophage populations and phenotypes associated with IL-4 mediated immunomodulation at the host implant interface.

The host macrophage response to implants has shown to be affected by tissue location and physio-pathological conditions of the patient. Success in immunomodulatory strategies is thus predicated on the proper understanding of the macrophage populations participating on each one of these contexts. The present study uses an in vivo implantation model to analyze how immunomodulation via an IL-4 eluting implant affects distinct macrophage populations at the tissue-implant interface and how this may affect downstream regenerative processes. Populations identified as F4/80+, CD68+ and CD11b+ macrophages at the peri-implant space showed distinct susceptibility to polarize towards an M2-like phenotype under the effects of delivered IL-4. Also, the presence of the coating resulted in a significant reduction in F4/80+ macrophages, while other populations remained unchanged. These results suggests that the F4/80+ macrophage population may be predominant in the early stages of the host response at the surface of these implants, in contrast to CD11b+ macrophage populations which were either fewer in number or located more distant from the implant surface. Gene expression assays showed increased proteolytic activity and diminished matrix deposition as possible mechanisms explaining the decreased fibrotic capsule deposition and improved peri-implant tissue quality shown in previous studies using IL-4 eluting coatings. The pattern of M2-like gene expression promoted by IL-4 was correlated with glycosaminoglycan production within the site of implantation at early stages of the host response, suggesting a significant role in this response. These findings demonstrate that immunomodulatory strategies can be utilized to design and implement targeted delivery for improving biomaterial performance.

Frailty predicts mortality and complications in chronologically young patients with traumatic orthopaedic injuries.

BACKGROUND: As morbidity and mortality from traumatic orthopaedic injuries continues to rise, increased research is being conducted on how to best predict complications in at risk patients. Recently, frailty indices have been validated in a variety of surgical subspecialties as predictors of morbidity and mortality. However, the vast majority of research has been conducted on geriatric patient populations, with little evidence on patients who are chronologically young. The purpose of this study was to evaluate the role of a modified frailty index (mFI) in predicting mortality and complications after pelvis, acetabulum, and lower extremity trauma in patients of all ages. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was queried from 2005 to 2014 for all patients who underwent surgery for pelvis, acetabulum, and lower extremity trauma. The sample size was divided into geriatric (age ≥ 60) and young (age < 60) cohorts. The mFI score was calculated for each patient. Bivariate analysis was performed using logistic regression and a chi-square test to determine the relationship between mFI and both primary and secondary outcomes while adjusting for age. Univariate analysis and multivariate analyses were performed. All analyses were done using SAS 9.4 (Cary, NC) and a p < 0.05 was considered significant. RESULTS: 56,241 patients were identified to have undergone surgery for pelvis, acetabulum, or lower extremity trauma. 28% of patients were identified under the age of 60. In the young cohort, mFI was a strong predictor of thirty-day mortality (OR 11.02, 95% CI 6.26-19.39, p < 0.001). With regards to Clavien-Dindo grade IV complications, MFI is also a strong predictor in the young cohort (OR 28.82, 95% CI 16.05-51.77, p < 0.001). CONCLUSION AND RELEVANCE: The mFI score was a significant predictor of morbidity and mortality in chronologically young orthopaedic trauma patients. The use of the mFI score can provide an individualized risk assessment to interdisciplinary teams for perioperative counseling and to improve outcomes.

Neurovascular toxicity of N-methyl-d-aspartate is markedly enhanced in the developing mouse central nervous system.

Penumbral perfusion is critical to brain viability. Proximal arterial occlusion and deep brain stroke has variable effect on cortical dysfunction. Cortical microvessel collaterals may be recruited and at times sufficient for partial parenchymal perfusion. Postnatal neural and endothelial cells are markedly vulnerable to glutamate excitotoxicity. Early vascular cell stress may promote partial protective neural preconditioning though postnatally a developmental window of the cerebral microvasculature may be particularly vulnerable to injury. We tested the hypothesis that postnatal NMDA excitotoxic injury, when cerebral endothelial cells' central energy source is via glycolysis, is age specific. Neurovascular responses of cortical viability were directly identified with diffuse reflectance patterns of perfusion properties in a non-invasive manner, over time. Histological evaluation for neural and vascular cytoarchitectonic abnormalities were evaluated 4- 7days post injury. Optical diffuse reflectance recordings were obtained at the injection site prior to, immediately after and 48h post injury. Extent of neurovascular injury at the infarct zone was greatest at PND 5 and cortical perfusion responses identified with recordings of pattern change. These data further suggest excitotoxic injury to both neural and vascular cells, in vivo, can enhance CNS injury in the young and neuroprotective strategies may benefit from vascular directed therapies.

Effects of aging upon the host response to implants.

Macrophage polarization during the host response is now a well-accepted predictor of outcomes following material implantation. Immunosenescence, dysregulation of macrophage function, and delayed resolution of immune responses in aged individuals have all been demonstrated, suggesting that host responses to materials in aged individuals should differ from those in younger individuals. However, few studies examining the effects of aging upon the host response have been performed. The present work sought to elucidate the impacts of aging upon the host response to polypropylene mesh implanted into 8-week-old and 18-month-old mice. The results showed that there are significant differences in macrophage surface marker expression, migration, and polarization during the early host macrophage response and delayed resolution of the host response in 18-month-old versus 8-week-old mice. These differences could not be attributed to cell-intrinsic defects alone, suggesting that the host macrophage response to implants is likely also dictated to a significant degree by the local tissue microenvironment. These results raise important questions about the design and testing of materials and devices often intended to treat aged individuals and suggest that an improved understanding of patient- and context-dependent macrophage responses has the potential to improve outcomes in aged individuals. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1281-1292, 2017.