Determining the Impact of the COVID-19 Pandemic on Hand Surgery Fellowship Education.

The purpose of this study is to report the impact of COVID-19 on hand surgery fellow learning and preparedness for practice. A multi-dimensional questionnaire was distributed to current hand fellows and fellowship directors across the United States. Survey questions included fellowship location, institutional response, impact on practice, education and job search. Thirty-two hand surgery fellows and 14 fellowship directors completed the survey. Of fellows, 59% reported a greater than 75% decrease in case volume. Mean hours worked per week per fellow decreased by 52%. All fellowship directors and 94% of fellows did not expect COVID-19 to impact their ability to graduate, and nearly all fellows felt prepared to start practice after fellowship training. However, many fellows expressed concern about job opportunities. The work hours and exposure of hand surgery fellows to elective surgical cases have been adversely impacted by COVID-19. Nevertheless, current hand fellows feel prepared to enter practice. (Journal of Surgical Orthopaedic Advances 31(1):048-052, 2022).

Performance assessment of two motion management systems for frameless stereotactic radiosurgery.

BACKGROUND/PURPOSE: Frameless stereotactic radiosurgery (SRS) requires dedicated systems to monitor patient motion in order to avoid inaccurate radiation delivery due to involuntary shifts. The purpose of this study is to assess the accuracy and sensitivity of two distinct motion monitoring systems used for frameless SRS. METHODS: A surface image-guided system known as optical surface monitoring system (OSMS), and a fiducial marker-based system known as high definition motion management (HDMM) as part of the latest Gamma Knife Icon® were compared. A 3D printer-based cranial motion phantom was developed to evaluate the accuracy and sensitivity of these two systems in terms of: (1) the capability to recognize predefined shifts up to 3 cm, and (2) the capability to recognize predefined speeds up to 3 cm/s. The performance of OSMS, in terms of different reference surfaces, was also evaluated. RESULTS: Translational motion could be accurately detected by both systems, with an accuracy of 0.3 mm for displacement up to 1 cm, and 0.5 mm for larger displacements. The reference surface selection had an impact on OSMS performance, with flat surface resulting in less accuracy. HDMM was in general more sensitive when compared with OSMS in capturing the motion, due to its faster frame rate, but a delay in response was observed with faster speeds. Both systems were less sensitive in detection of superior-inferior motion when compared to lateral or vertical displacement directions. CONCLUSION: Translational motion can be accurately and sensitively detected by OSMS and HDMM real-time monitoring systems. However, performance variations were observed along different motion directions, as well as amongst the selection of reference images. Caution is needed when using real-time monitoring systems for frameless SRS treatment.

COVID-19 and the rise of virtual medicine in spine surgery: a worldwide study.

PURPOSE: The COVID-19 pandemic forced many surgeons to adopt "virtual medicine" practices, defined as telehealth services for patient care and online platforms for continuing medical education. The purpose of this study was to assess spine surgeon reliance on virtual medicine during the pandemic and to discuss the future of virtual medicine in spine surgery. METHODS: A comprehensive survey addressing demographic data and virtual medicine practices was distributed to spine surgeons worldwide between March 27, 2020, and April 4, 2020. RESULTS: 902 spine surgeons representing seven global regions responded. 35.6% of surgeons were identified as "high telehealth users," conducting more than half of clinic visits virtually. Predictors of high telehealth utilization included working in an academic practice (OR = 1.68, p = 0.0015) and practicing in Europe/North America (OR 3.42, p < 0.0001). 80.1% of all surgeons were interested in online education. Dedicating more than 25% of one's practice to teaching (OR = 1.89, p = 0.037) predicted increased interest in online education. 26.2% of respondents were identified as "virtual medicine surgeons," defined as surgeons with both high telehealth usage and increased interest in online education. Living in Europe/North America and practicing in an academic practice increased odds of being a virtual medicine surgeon by 2.28 (p = 0.002) and 1.15 (p = 0.0082), respectively. 93.8% of surgeons reported interest in a centralized platform facilitating surgeon-to-surgeon communication. CONCLUSION: COVID-19 has changed spine surgery by triggering rapid adoption of virtual medicine practices. The demonstrated global interest in virtual medicine suggests that it may become part of the "new normal" for surgeons in the post-pandemic era.

Learning from the past: did experience with previous epidemics help mitigate the impact of COVID-19 among spine surgeons worldwide?

PURPOSE: Spine surgeons around the world have been universally impacted by COVID-19. The current study addressed whether prior experience with disease epidemics among the spine surgeon community had an impact on preparedness and response toward COVID-19. METHODS: A 73-item survey was distributed to spine surgeons worldwide via AO Spine. Questions focused on: demographics, COVID-19 preparedness, response, and impact. Respondents with and without prior epidemic experience (e.g., SARS, H1NI, MERS) were assessed on preparedness and response via univariate and multivariate modeling. Results of the survey were compared against the Global Health Security Index. RESULTS: Totally, 902 surgeons from 7 global regions completed the survey. 24.2% of respondents had prior experience with global health crises. Only 49.6% reported adequate access to personal protective equipment. There were no differences in preparedness reported by respondents with prior epidemic exposure. Government and hospital responses were fairly consistent around the world. Prior epidemic experience did not impact the presence of preparedness guidelines. There were subtle differences in sources of stress, coping strategies, performance of elective surgeries, and impact on income driven by prior epidemic exposure. 94.7% expressed a need for formal, international guidelines to help mitigate the impact of the current and future pandemics. CONCLUSIONS: This is the first study to note that prior experience with infectious disease crises did not appear to help spine surgeons prepare for the current COVID-19 pandemic. Based on survey results, the GHSI was not an effective measure of COVID-19 preparedness. Formal international guidelines for crisis preparedness are needed to mitigate future pandemics.

Correction to: Learning from the past: did experience with previous epidemics help mitigate the impact of COVID-19 among spine surgeons worldwide?

Unfortunately, the 13th author name has been incorrectly published in the original publication. The complete correct name is given below.

Disparities in Hip Arthroplasty Outcomes: Results of a Statewide Hospital Registry From 2016 to 2018.

BACKGROUND: In November 2019, Centers for Medicare and Medicaid Services announced total hip arthroplasty (THA) will be removed from the inpatient-only list. This may lead to avoidance of patients who have prolonged hospitalizations and discharge to skilled nursing facilities or push providers to unsafely push patients to outpatient surgery centers. Disparities in hip arthroplasty may worsen as patients are "risk stratified" preoperatively to minimize cost outliers. We aimed to evaluate which patient characteristics are associated with extended length of stay (eLOS)-greater than 2 days-and nonhome discharge in patients undergoing hip arthroplasty. METHODS: The Illinois COMPdata administrative database was queried for THA admissions from January 2016 to June 2018. Variables included age, sex, race and ethnicity, median household income, Illinois region, insurance status, principal diagnosis, Charlson comorbidity index, obesity, discharge disposition, and LOS. Hospital characteristics included bundled payment participation and arthroplasty volume. Using multiple Poisson regression, we examined the association between these factors and the likelihood of nonhome discharge and eLOS. RESULTS: There were 41,832 THA admissions from January 2016 to June 2018. A total of 36% had LOS greater than 2 midnights and 25.3% of patients had nonhome discharges. Female patients, non-Hispanic black patients, patients older than 75, obese patients, Medicaid or uninsured status, Charlson comorbidity index > 3, and hip arthroplasty for fracture were associated with increased risk of eLOS and/or nonhome discharge (P < .05). CONCLUSION: With the Centers for Medicare and Medicaid Services emphasis on cost containment, patients at risk of extended stay or nonhome discharge may be deemed "high risk" and have difficulty accessing arthroplasty care. These are potentially vulnerable groups during the transition to the bundled payment model.

Automatic measurement of air gap for proton therapy using orthogonal x-ray imaging with radiopaque wires.

PURPOSE: The main objective of this study was to develop a technique to accurately determine the air gap between the end of the proton beam compensator and the body of the patient in proton radiotherapy. METHODS: Orthogonal x-ray image-based automatic coordinate reconstruction was used to determine the air gap between the patient body surface contour and the end of beam nozzle in proton radiotherapy. To be able to clearly identify the patient body surface contour on the orthogonal images, a radiopaque wire was placed on the skin surface of the patient as a surrogate. In order to validate this method, a Rando® head phantom was scanned and five proton plans were generated on a Mevion S250 Proton machine with various air gaps in Varian Eclipse Treatment Planning Systems (TPS). When setting up the phantom in a treatment room, a solder wire was placed on the surface of the phantom closest to the beam nozzle with the knowledge of the beam geometry in the plan. After the phantom positioning was verified using orthogonal kV imaging, the last pair of setup kV images was used to segment the solder wire and the in-room coordinates of the wire were reconstructed using a back-projection algorithm. Using the wire as a surrogate of the body surface, we calculated the air gaps by finding the minimum distance between the reconstructed wire and the end of the compensator. The methodology was also verified and validated on clinical cases. RESULTS: On the phantom study, the air gap values derived with the automatic reconstruction method were found to be within 1.1 mm difference from the planned values for proton beams with air gaps of 85.0, 100.0, 150.0, 180.0, and 200.0 mm. The reconstruction technique determined air gaps for a patient in two clinical treatment sessions were 38.4 and 41.8 mm, respectively, for a 40 mm planned air gap, and confirmed by manual measurements. There was strong agreement between the calculated values and the automatically measured values, and between the automatically and manually measured values. CONCLUSIONS: An image-based automatic method has been developed to conveniently determine the air gap of a proton beam, directly using the orthogonal images for patient positioning without adding additional imaging dose to the patient. The method provides an objective, accurate, and efficient way to confirm the target depth at treatment to ensure desired target coverage and normal tissue sparing.

Which Postoperative Day After Total Joint Arthroplasty Are Catastrophic Events Most Likely to Occur?

BACKGROUND: Despite lacking granularity, large database registries can help provide important information on rare outcomes following total joint arthroplasty (TJA). In an era of short stay and outpatient arthroplasty, an awareness of the timeframe for most common catastrophic complications can help providers maintain an appropriate degree of suspicion for these significant events. METHODS: Patients undergoing primary TJA between 2011 and 2016 were identified in the National Surgical Quality Improvement Program and queried for 4 adverse postoperative outcomes: pulmonary embolism (PE), myocardial infarction or cardiac arrest, cerebrovascular accident, and death. The timing of postoperative events was compared, and also their association with medical comorbidities and timing in inpatient vs outpatient arthroplasty. RESULTS: A total of 341,601 patients met inclusion criteria. Of them, 1631 (0.48%) patients sustained a postoperative PE, 1033 (0.3%) patients had a cardiac event, 304 patients had a cerebrovascular accident (0.09%), and 608 (0.18%) patients expired. Greater than 60% of all these complications occurred between postoperative days 0 and 5, including 65% of PE. On postoperative day 0, a catastrophic event is 13 times more likely to be a cardiac event (80.7%) compared to a PE (6%). However, by postoperative day 1, a cardiac event (41.2%) is only 1.03 times more likely than a PE (40%) and by postoperative day 2, a PE (62%) is twice as likely as a cardiac event (30%). CONCLUSION: Risk assessment for catastrophic event and timeliness of occurrence may guide providers to recommend enhanced observation for specific patients undergoing TJA.

Aryl Hydrocarbon Receptor Antagonists Mitigate the Effects of Dioxin on Critical Cellular Functions in Differentiating Human Osteoblast-Like Cells.

The inhibition of bone healing in humans is a well-established effect associated with cigarette smoking, but the underlying mechanisms are still unclear. Recent work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR) as a mediator of the anti-osteogenic effects of cigarette smoke, but the complexity of cigarette smoke mixtures makes understanding the mechanisms of action a major challenge. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity AhR ligand that is frequently used to investigate biological processes impacted by AhR activation. Since there are dozens of AhR ligands present in cigarette smoke, we utilized dioxin as a prototype ligand to activate the receptor and explore its effects on pro-osteogenic biomarkers and other factors critical to osteogenesis using a human osteoblast-like cell line. We also explored the capacity for AhR antagonists to protect against dioxin action in this context. We found dioxin to inhibit osteogenic differentiation, whereas co-treatment with various AhR antagonists protected against dioxin action. Dioxin also negatively impacted cell adhesion with a corresponding reduction in the expression of integrin and cadherin proteins, which are known to be involved in this process. Similarly, the dioxin-mediated inhibition of cell migration correlated with reduced expression of the chemokine receptor CXCR4 and its ligand, CXCL12, and co-treatment with antagonists restored migratory capacity. Our results suggest that AhR activation may play a role in the bone regenerative response in humans exposed to AhR activators, such as those present in cigarette smoke. Given the similarity of our results using a human cell line to previous work done in murine cells, animal models may yield data relevant to the human setting. In addition, the AhR may represent a potential therapeutic target for orthopedic patients who smoke cigarettes, or those who are exposed to secondhand smoke or other environmental sources of aryl hydrocarbons.

Patterns of adjuvant radiation usage and survival outcomes for stage I endometrial carcinoma in a large hospital-based cohort.

OBJECTIVE: Two randomized trials have demonstrated a local control advantage in the absence of a survival advantage for the addition of adjuvant radiation therapy (RT) to surgery in patients with stage I endometrial adenocarcinoma (EC). This study analyzed the National Cancer Data Base (NCDB) to evaluate the impact of adjuvant RT on overall survival (OS) for patients with stage I EC. METHODS: Patients with EC who underwent total hysterectomy/bilateral salpingo-oophorectomy between 2004 and 2011 were queried. Only those with AJCC stage pT1N0M0 were included. Patients surviving <4months excluded. Adjuvant RT included external beam RT (EBRT), brachytherapy, or external RT+brachytherapy. OS was analyzed using the Kaplan-Meier method. Multivariate Cox regression analysis and propensity matched analysis were performed to assess the impact of covariates on OS. RESULTS: There were 61,697 patients included. Most women (83.9%) did not receive adjuvant RT. Adjuvant RT usage increased with increasing stage/grade. Usage of brachytherapy alone decreased with increasing stage/grade (78.2% for IA/G1 to 36.1% for IB/G3) corresponding to an increase in the use of EBRT (21.8% for IA/G1 to 53.9% for IB/G3). On multivariable analysis, adjuvant EBRT (HR 0.83, 95%CI 0.74-0.93, p=0.002) and brachytherapy (HR 0.82, 95%CI 0.74-0.93, p=0.002) were each associated with improved survival for women with stage IB. In the propensity matched cohort, RT was associated with improved survival (0.85, 95% CI 0.78-0.92, p<0.001). CONCLUSION: The use of adjuvant RT for women with stage I EC is highly dependent on stage/grade and is associated with improved survival for stage IB.

A Comparison of Outcomes Between Open Hysterectomy and Robotic-Assisted Hysterectomy for Endometrial Cancer Using the National Cancer Database.

PURPOSE: The purpose of this study is to evaluate usage patterns and outcomes of women who underwent open hysterectomy (OH) versus robotic assisted-hysterectomy (RAH) for the treatment of endometrial cancer. METHODS: Women with nonmetastatic endometrial adenocarcinoma diagnosed between 2010 and 2012, who either underwent an OH or RAH, were selected from the National Cancer Database. The χ, Fisher exact, or Mann-Whitney U tests were used where appropriate to compare outcomes between groups. Multivariable logistic regression was used to analyze for predictors for RAH and other outcome variables. RESULTS: A total of 43,985 women were included in this study with a median age of 61 years. Of these, 23,872 (54.3%) underwent RAH and 20,113 (45.7%) underwent OH. The usage of RAH increased from 43.0% in 2010 to 63.8% in 2012 (P < 0.001). Women receiving RAH were more commonly found to have a Charlson comorbidity score of 0 to 1, lower pathologic stage, nonblack race, treatment at a comprehensive center, and had insurance other than Medicaid. Robotic-assisted hysterectomy was associated with a shorter inpatient stay, lower readmission rates, and lower 30- and 90-day mortality rates (P < 0.001 for all comparisons). There was a significant improvement in overall survival favoring RAH, 96.1% versus 94.0%, which persisted on multivariable logistic regression (P < 0.001). CONCLUSIONS: In this large, hospital-based analysis, RAH was associated with decreased length of stay, lower readmission rates, and less perioperative mortality. However, socioeconomic status continues to remain a barrier to equal treatment allocation. Overall survival was improved with RAH, but the follow-up is limited, and this finding must be interpreted with caution.

Patterns of care and survival outcomes in the treatment of esophageal melanoma.

Because of the rarity of esophageal melanoma, the optimal management of this disease is limited. The pooled dataset in the National Cancer Database (NCDB) was used to identify the prognostic factors and treatment outcomes. Patients who were diagnosed with esophageal melanoma between 2004 and 2011 were identified. Patients were stratified as either localized (T1-4N0M0), regional (T1-4N+M0), or metastatic (M1). The primary endpoint of this study was overall survival (OS) which was analyzed using the Kaplan-Meier method and multivariate Cox regression, which was performed to identify potential factors influencing survival. A total of 56 patients were identified with median follow-up of 10.2 months. Twenty-seven (48.2%) patients had localized disease, 10 patients (17.9%) had regional disease, and 19 patients (33.9%) were metastatic at diagnosis. For those with localized disease, the 3 year OS was 50.5% for the 14 patients treated with esophagectomy, and 0.0% for the seven treated with definitive radiation therapy. For regional disease, the 3 year OS was 11.1% for the nine patients treated with esophagectomy. The 3 year OS for those with metastatic disease at diagnosis was 0.0%. On multivariate analysis, treatment with esophagectomy was not associated with a reduced risk of death (HR 0.84, 95% CI 0.31-2.25, P = 0.73), while regional disease (HR 3.78, 95% CI 1.40-10.19, P = 0.009) and metastatic disease (HR 7.54, 95% CI 2.89-19.62, P < 0.001) were associated with decreased survival. Esophageal melanoma is an extremely rare and aggressive disease with very poor outcomes. Esophagectomy may result in reasonable survival for localized disease.

Utilization of adjuvant therapies and their impact on survival for women with stage IIIC endometrial adenocarcinoma.

PURPOSE/OBJECTIVES: Adjuvant treatment options following surgical staging for women with stage IIIC endometrial carcinoma include chemotherapy (CT) with or without radiation therapy (RT). We utilized the National Cancer Database (NCDB) to investigate utilization of adjuvant CT and RT for this group of patients and assess their impact on overall survival (OS). MATERIALS/METHODS: The NCDB was queried for patients diagnosed with non-metastatic surgically staged uterine adenocarcinoma between 2004 and 2011 with at least one pathologically positive lymph node. Overall survival (OS) was analyzed using the Kaplan-Meier method. Comparison was made between patients receiving no additional therapy, RT alone, CT alone, or a combination of CT and RT (CMT). Multivariable cox regression analysis (MVA) was performed to evaluate the effect of covariates on OS. RESULTS: A total of 6720 patients were included in this study. Of whom, 1409 received no adjuvant treatment, 1533 received CT only, 1265 received RT only, and 2522 received CMT. The 5-year OS for patients receiving no adjuvant therapy, RT alone, CT alone, and CMT were 54.9%, 63.9%, 64.4%, and 72.6%, respectively. On pairwise analysis, CMT was associated with improved survival compared to all other subgroups (p<0.001). On MVA, CMT (HR 0.58, 95% CI 0.52-0.66, p<0.001) was the strongest predictor for improved OS compared to RT alone (HR 0.79, 95% CI 0.69-0.89, p<0.001) or CT alone (HR 0.75, 95% CI 0.66-0.85, p<0.001). CONCLUSIONS: Both adjuvant CT and adjuvant RT were associated with improved OS for women with stage IIIC endometrial adenocarcinoma, but CMT was associated with the largest improvement in OS.

Roussouly classification of adult spinal deformity.

With an estimated prevalence of 68% among healthy adults without a previous diagnosis of scoliosis, adult spinal deformities are a growing concern as the population ages. Our understanding of this growing concern has been historically guided by previous studies performed on the pediatric population. Over time, different classifications have been developed with their own respective limitations. The Roussouly classification was the first classification to describe the shapes of an asymptomatic spine. It considers lumbar lordosis, pelvic incidence, and the inflection point from lumbar lordosis to thoracic kyphosis to attempt to stratify the shapes of an asymptomatic spine. This classification aims to guide treatment, provide information regarding prognosis, allow stratification for research, and be highly reproducible. Overall, the Roussouly classification is a novel way to think about sagittal malalignment, considering the patient's individual anatomy, while allowing for communication between surgeons. Additionally, it has proven to be a reliable system that provides prognostic value for clinicians and may minimize complications when a patient's sagittal alignment is optimized using this classification system.

Case-Based Specialty Training for Medical Students to Elicit Social Determinants of Health.

Introduction: Without explicit education and training on how social determinants of health (SDoH) impact patient care and health outcomes, medical schools are failing to effectively equip future physicians to serve their patients. We created this workshop on health equity with a focus on SDoH to help students more effectively communicate with diverse populations. Methods: Third-year medical students and faculty were provided with class guides, learning objectives, role-play vignettes containing clerkship-specific history and physical exams, schedules, and discussion questions during a 2-hour session centered on SDoH. The workshop's impact was measured through mixed-methods analysis of surveys. Results: Based on pre- and postsurvey results from 87 participants, medical students strongly agreed that (1) SDoH factor more into a patient's health outcomes than the clinical encounter (pre: 67%, post: 87%), (2) it is their duty to gather information about SDoH (pre: 86%, post: 97%), (3) neighborhood safety is one of the key SDoH (pre: 88%, post: 97%), (4) they understood the impact of upstream interventions (pre: 35%, post: 93%), (5) they could efficiently screen all patients for SDoH at every medical encounter (pre: 27%, post: 86%), and (6) they could find preliminary resources to quickly assist patients in need of help regarding particular SDoH (pre: 26%, post: 85%). Discussion: This was the first iteration of this workshop; challenges involved piloting the content, time restraints, and organizational structure of the workshop design. Future directions include making SDoH curricula an integral part of undergraduate medical education and diverse clinical environments.

Teaching Second-Year Medical Students How to Counsel Pediatric Patients With Unhealthy Body Mass Index.

Obesity affects the health and well-being of children globally. Despite recommendations to routinely screen children for obesity starting at age 6 years, physicians do not consistently address weight or provide effective weight-management counseling. We developed an interactive session for second-year medical students with foundational knowledge and practical communication skills around partnership and discussion of pediatric healthy weight management. Students were administered a pre-/post-Likert survey to self-assess knowledge, comfort, and confidence in counseling patients and caregivers about weight management. Students' related counseling skills were assessed during a standardized patient encounter of a teen with rapid weight gain. The session successfully increased students' self-assessed knowledge, comfort, and confidence, and resulted in successful application of weight management skills in a simulated patient encounter. Utilization of empathy skills requires continued coaching. We propose incorporation of similar sessions into medical school curricula to address the pediatric obesity epidemic.

Social Media Posts Pertaining to Anterior Cervical Discectomy and Fusion (ACDF) Surgery: A Cross-sectional Analysis of Patient and Surgeon Perceptions.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To analyze publicly available content on a major social media outlet related to anterior cervical discectomy and fusion (ACDF) surgery based on perspective, location, timing, content, tone, and patient satisfaction. SUMMARY OF BACKGROUND DATA: Social media offers a powerful platform for sharing the patient experience with the public through an unfiltered perspective. Social media content may influence future perceptions around surgical care and postings around ACDF have not been previously reported. METHODS: A query of content from a major social media outlet was performed for the study period January 1, 2018, to January 1, 2020, and returned 6500 publicly available posts. Content was identified by the hashtags "#acdf" or "#acdfsurgery." Content was ranked by number of "likes." Of the 1500 most popular posts, 1136 related to ACDF surgery and were included. Post content was characterized and classified. RESULTS: Patients created 85% of ACDF-related content and spine surgeons created 11.8%. Most posts portrayed the patient experience in the postoperative period and depicted patients performing activities of daily living, participating in sports, or completing work activities (54.4%). The connotation of posts was deemed to be positive in 79.2% of cases. In regard to their care or state of health as it related to ACDF surgery, 59.8% of patients expressed satisfaction, whereas 14.1% expressed dissatisfaction. Female patients were >4 times as likely to express dissatisfaction (odds ratio=4.16, P =<0.0001), with their clinical course compared with their male counterparts. CONCLUSIONS: Patients were the source of most posts on a major social media outlet that pertained to ACDF surgery with a majority reporting positive tone and satisfaction. These mechanisms of communication offer surgeons unique insights into patient experience and may provide an opportunity for surgeons to assess patient feedback, influence patient perceptions, and enhance delivery of cervical spine care.

A supramolecular polymer-collagen microparticle slurry for bone regeneration with minimal growth factor.

Recombinant bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive growth factor that can promote bone regeneration for challenging skeletal repair and even for ectopic bone formation in spinal fusion procedures. However, serious clinical side effects related to supraphysiological dosing highlight the need for advances in novel biomaterials that can significantly reduce the amount of this biologic. Novel biomaterials could not only reduce clinical side effects but also expand the indications for use of BMP-2, while at the same time lowering the cost of such procedures. To achieve this objective, we have developed a slurry containing a known supramolecular polymer that potentiates BMP-2 signaling and porous collagen microparticles. This slurry exhibits a paste-like consistency that stiffens into an elastic gel upon implantation making it ideal for minimally invasive procedures. We carried out in vivo evaluation of the novel biomaterial in the rabbit posterolateral spine fusion model, and discovered efficacy at unprecedented ultra-low BMP-2 doses (5 µg/implant). This dose reduces the growth factor requirement by more than 100-fold relative to current clinical products. This observation is significant given that spinal fusion involves ectopic bone formation and the rabbit model is known to be predictive of human efficacy. We expect the novel biomaterial can expand BMP-2 indications for difficult cases requiring large volumes of bone formation or involving patients with underlying conditions that compromise bone regeneration.

Evaluation of Biological Effective Dose in Gamma Knife Staged Stereotactic Radiosurgery for Large Brain Metastases.

Objective: Gamma knife (GK) staged stereotactic radiosurgery (Staged-SRS) has become an effective treatment option for large brain metastases (BMs); however, it has been challenging to evaluate the total dose because of tumor shrinkage between two staged sessions. This study aims to evaluate total biological effective dose (BED) in Staged-SRS, and to compare the BED with those in single-fraction SRS (SF-SRS) and hypo-fractionated SRS (HF-SRS). Methods: Patients treated with GK Staged-SRS at a single institution were retrospectively included. The dose delivered in two sessions of Staged-SRS was summed using the deformable image registration. Each patient was replanned for SF-SRS and HF-SRS. The total BEDs were computed using the linear-quadratic model. Tumor BED98% and brain V84Gy2, equivalent to V12Gy in SF-SRS, were compared between SF-SRS, HF-SRS, and Staged-SRS plans with the Wilcoxon test. Results: Twelve patients with 24 BMs treated with GK Staged-SRS were identified. We observed significant differences (p < 0.05) in tumor BED98% but comparable brain V84Gy2 (p = 0.677) between the Staged-SRS and SF-SRS plans. No dosimetric advantages of Staged-SRS over HF-SRS were observed. Tumor BED98% in the HF-SRS plans were significantly higher than those in the Staged-SRS plans (p < 0.05). Despite the larger PTVs, brain V84Gy2 in the HF-SRS plans remained lower (p < 0.05). Conclusion: We presented an approach to calculate the composite BEDs delivered to both tumor and normal brain tissue in Staged-SRS. Compared to SF-SRS, Staged-SRS delivers a higher dose to tumor but maintains a comparable dose to normal brain tissue. Our results did not show any dosimetric advantages of Staged-SRS over HF-SRS.