Survival outcomes in pediatric patients with metastatic Ewing sarcoma who achieve a rapid complete response of pulmonary metastases.

PURPOSE: Our objectives were to compare overall survival (OS) and pulmonary relapse between patients with metastatic Ewing sarcoma (EWS) at diagnosis who achieve rapid complete response (RCR) and those with residual pulmonary nodules after induction chemotherapy (non-RCR). PATIENTS AND METHODS: This retrospective cohort study included children under 20 years with metastatic EWS treated from 2007 to 2020 at 19 institutions in the Pediatric Surgical Oncology Research Collaborative. Chi-square tests were conducted for differences among groups. Kaplan-Meier curves were generated for OS and pulmonary relapse. RESULTS: Among 148 patients with metastatic EWS at diagnosis, 61 (41.2%) achieved RCR. Five-year OS was 71.2% for patients who achieved RCR, and 50.2% for those without RCR (p = .04), and in multivariable regression among patients with isolated pulmonary metastases, RCR (hazards ratio [HR] 0.42; 95% confidence interval [CI]: 0.17-0.99) and whole lung irradiation (WLI) (HR 0.35; 95% CI: 0.16-0.77) were associated with improved survival. Pulmonary relapse occurred in 57 (37%) patients, including 18 (29%) in the RCR and 36 (41%) in the non-RCR groups (p = .14). Five-year pulmonary relapse rates did not significantly differ based on RCR (33.0%) versus non-RCR (47.0%, p = .13), or WLI (38.8%) versus no WLI (46.0%, p = .32). DISCUSSION: Patients with EWS who had isolated pulmonary metastases at diagnosis had improved OS if they achieved RCR and received WLI, despite having no significant differences in rates of pulmonary relapse.

Proliferative Effects of Mesenchymal Stromal Cells on Neuroblastoma Cell Lines: Are They Tumor Promoting or Tumor Inhibiting?

BACKGROUND: Neuroblastoma is a common pediatric malignancy with poor survival for high-risk disease. Mesenchymal stromal cells (MSCs) have innate tumor-homing properties, enabling them to serve as a cellular delivery vehicle, but MSCs have demonstrated variable effects on tumor growth. We compared how placental MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) affect proliferation of neuroblastoma (NB) cells in vitro. METHODS: Indirect co-culture assessed proliferative effects of 18 MSCs (early-gestation PMSCs (n = 9), term PMSCs (n = 5), BM-MSCs (n = 4) on three high-risk NB cell lines (NB1643, SH-SY5Y, and CHLA90). Controls were NB cells cultured in media alone. Proliferation was assessed using MTS assay and measured by fold change (fc) over controls. PMSCs were sub-grouped by neuroprotective effect: strong (n = 7), intermediate (n = 3), and weak (n = 4). The relationship between MSC type, PMSC neuroprotection, and PMSC gestational age on NB cell proliferation was assessed. RESULTS: NB cell proliferation varied between MSC groups. BM-MSCs demonstrated lower proliferative effects than PMSCs (fc 1.18 vs 1.44, p < 0.001). Neither gestational age nor neuroprotection significantly predicted degree of proliferation. Proliferative effects of MSCs varied among NB cell lines. BM-MSCs had less effect on CHLA90 (fc 1.01) compared to NB1643 (fc 1.33) and SH-SY5Y (fc 1.20). Only NB1643 showed a difference between early and term PMSCs (p = 0.04). CONCLUSION: Effects of MSCs on NB cell proliferation vary by MSC source and NB cell line. BM-MSCs demonstrated lower proliferative effects than most PMSCs. MSC neuroprotection was not correlated with proliferation. Improved understanding of MSC proliferation-promoting mechanisms may provide valuable insight into selection of cells best suited as drug delivery vehicles. LEVEL OF EVIDENCE: N/A. TYPE OF STUDY: Original Research.

Development of a Simple and Reproducible Cell-derived Orthotopic Xenograft Murine Model for Neuroblastoma.

BACKGROUND/AIM: Neuroblastoma is a common childhood cancer with poor survival for children with high-risk disease, and ongoing research to improve outcomes is needed. Patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM) are reliable models for oncologic research; however, they are resource-intensive, expensive, and require significant expertise to develop and maintain. We developed an orthotopic xenograft murine model of neuroblastoma that utilizes cryopreserved banks of human neuroblastoma cell lines, requires minimal equipment, and is easily reproducible. MATERIALS AND METHODS: The neuroblastoma cell line NB1643 was obtained from the Children's Oncology Group (COG) Childhood Cancer Repository. Nod-SCID-gamma (NSG) mice underwent orthotopic injection of 2x106 NB1643 cells suspended in 10 µl of collagen hydrogel directly into the adrenal gland via an open retroperitoneal surgical approach. Mice were monitored by ultrasound and in vivo imaging system (IVIS) until the tumor reached the volume of the ipsilateral kidney. Tumor identity was confirmed by necropsy and histologic analysis. RESULTS: A total of 55 mice underwent surgery. Eight died due to anesthetic or surgical complications. 39/47 (78%) survivors grew primary adrenal tumors. Average anesthesia time was 30 min. Ultrasound and IVIS successfully characterized tumor growth in all mice. Average time to target tumor size was 5 weeks (range=3-9). Gross pathologic and histologic analysis confirmed adrenal tumors consistent with neuroblastoma in all mice with adrenal masses. CONCLUSION: A cell-derived orthotopic xenograft murine model can be successfully used to create an in vivo model of neuroblastoma. This model can be utilized in environments where PDX or GEMM models are not feasible.

Something Lost and Something Gained: Navigating the Bedside Teaching Role as a Hospice and Palliative Medicine Educator.

Hospice and palliative medicine (HPM) educators must often give up the satisfaction of working one-on-one with patients, to allow learners the opportunity to practice key communication skills and form their own therapeutic bonds with patients. Though the loss of that primary relationship with patients may feel challenging, educators may find new opportunity for professional impact and satisfaction by investing in their relationship with learners. This case discussion explores the challenges of bedside teaching in HPM, including the educator's looser connection with patients, need to withhold their own communication skills, and decision of when to interject into a trainee-patient conversation. We then propose strategies to help educators find renewed professional fulfillment in the teacher-learner relationship. By partnering intentionally with learners before, during, and after shared visits, inviting informal reflection between encounters, and preserving independent clinical time, we believe educators may cultivate a more sustainable and meaningful clinical teaching practice.

Building a Culture of Support at a Pediatric Surgery Center Through Multidisciplinary Peer Support.

INTRODUCTION: Surgeons and perioperative staff experience high rates of burnout manifesting as exhaustion, depersonalization, and lack of achievement. Consequences include increases in errors and adverse patient events. Little data exist regarding the effectiveness of multidisciplinary peer support systems in combatting burnout. We sought to improve staff morale through establishment of a formally trained, multidisciplinary peer support team. METHODS: Selfselected surgeons, anesthesiologists, and nurses were formally trained as Peer Responders as part of an institutional peer support program. All perioperative staff at our pediatric surgery center (n = 120) were surveyed before initiation of the program and then 1-mo and 12-mo after initiation. Primary outcomes were unit morale, unit support, and peer approachability. Kruskal-Wallis tests and Chi-squared tests were used for comparison of primary outcomes among surveys and by position with an alpha value of 0.05 set for significance. Institutional review board approval was waived. RESULTS: The survey response rates were 57.5%, 32.5%, and 37.5% chronologically. After 1 year, there were statistically significant increases in unit support (P < 0.01) and peer approachability (P < 0.001), and a nonstatistically significant increase in unit morale (P = 0.22). On subgroup analysis by staff role, surgeons were least likely to utilize peer support. CONCLUSIONS: A multidisciplinary peer support team is an effective and easily reproducible means of building a culture of support and improving morale among perioperative staff. Surgeons were least likely to seek interprofessional peer support. Consequently, surgeon-specific strategies may be necessary. Further investigations are ongoing regarding secondary effects on staff burnout rates, patient safety, and quality of care.

Increased Myocardial Infarction Risk Following Herpes Zoster Infection.

Background: Myocardial infarction (MI) has been reported as a postinfection sequela of herpes zoster, but with limited data on incidence after zoster and protective effect of the zoster vaccine. This study investigates the risk of developing an MI 30 days postzoster, determines patient-specific risk factors, and investigates the impact of herpes zoster vaccination. Methods: This retrospective cohort study included patients who received care at a Veterans Affairs facility between 2015 and 2020. Time to MI was determined from either 30 days post-zoster infection (zoster cohort) or a primary care appointment (control cohort). Results: This study assessed a total of 2 165 584 patients. MI within 30 days occurred in 0.34% (n = 244) of the zoster cohort and 0.28% (n = 5782) of the control cohort (P = .0016). Patients with a documented herpes zoster infection during the study period were 1.35 times more likely to develop an MI within the first 30 days postinfection compared to the control cohort. Patients who received the recombinant zoster vaccine were less likely to have an MI postinfection (odds ratio, 0.82 [95% confidence interval, .74-.92]; P = .0003). Conclusions: Herpes zoster infection was associated with an increased risk of MI within the first 30 days postinfection. History of prior MI, male sex, age ≥50 years, history of heart failure, peripheral vascular disease, human immunodeficiency virus, prior cerebrovascular accident, and renal disease increased odds of MI 30 days postinfection with herpes zoster. Herpes zoster vaccination decreased the odds of developing an MI in patients aged ≥50 years.

Effect of Training on Physicians' Palliative Care-Related Knowledge and Attitudes in Vietnam.

CONTEXT: Palliative care remains largely inaccessible in low- and middle-income countries (LMICs), and efforts to increase access are impeded by lack of training of proven effectiveness for physicians. OBJECTIVES: To measure the effectiveness of palliative care training for Vietnamese physicians. METHODS: The palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians were studied prior to a basic course in palliative care (baseline), just after the physicians completed the course (post), and 6-18 months later (follow-up). RESULTS: The self-assessment scores and knowledge scores increased significantly from baseline to post and decreased significantly from post to follow-up, but the follow-up scores remained significantly higher than baseline. There were significant interactions between changes over time of the knowledge scores and baseline age, degree, years of graduation, training, type of work, and whether participants had ever prescribed morphine for pain. Medically appropriate attitudes increased significantly from baseline to post and did not decrease significantly from post to follow-up. CONCLUSION: Our basic palliative care course in Vietnam resulted in significant and enduring improvements among physicians in palliative care-related knowledge, attitudes, and self-assessed competence. To respond to the enormous unmet need for palliative care in LMICs, primary care providers and physician-specialists in many fields, among others, should receive palliative care training of proven effectiveness, receive ongoing mentoring or refresher training, and be given the responsibility and opportunity to practice what they learn.

Increased Stroke Risk Following Herpes Zoster Infection and Protection With Zoster Vaccine.

BACKGROUND: Studies evaluating stroke following varicella zoster virus (VZV) infection are limited, and the utility of zoster vaccination against this phenomenon is unclear. This study aimed to determine the risk of stroke 30 days following zoster infection and to evaluate the impact of zoster vaccinations on the risk of stroke in VZV-infected patients. METHODS: This retrospective case-control study was conducted from January 2010 to January 2020 utilizing nationwide patient data retrieved from the Veterans Affairs' Corporate Data Warehouse. RESULTS: A total of 2 165 505 patients ≥18 years of age who received care at a Veterans Affairs facility were included in the study, of whom 71 911 had a history of zoster infection. Zoster patients were found to have 1.9 times increased likelihood of developing a stroke within 30 days following infection (odds ratio [OR], 1.93 [95% confidence interval {CI}, 1.57-2.4]; P < .0001). A decreased risk of stroke was seen in patients who received the recombinant zoster vaccine (OR, 0.57 [95% CI, .46-.72]; P < .0001) or the live zoster vaccine (OR, 0.77 [95% CI, .65-.91]; P = .002). CONCLUSIONS: Patients had a significantly higher risk of stroke within the first month following recent herpes zoster infection. Receipt of at least 1 zoster vaccination was found to mitigate this increased risk. Vaccination may therefore be viewed as a protective tool against the risk of neurologic postinfection sequelae.

Turning the Lens Inward: The Psychological Elements of Clinician Well Being.

This is the seventh entry in the Psychological Elements of Palliative Care (PEPC) series. Previous articles have focused on the psychological elements of the care we provide patients and the relationships we build with our referring clinician colleagues. In this entry, we focus on how the PEPC also impact clinician well being. The PEPC are bidirectional: we impact patients, but patients also impact us. The reactions that we have to patients and the boundaries we set around the care we provide are two examples of psychological factors of care that can influence our well being. Creating spaces to explore and reflect on the psychological impact of the clinical care we provide is a key component of wellness. Such spaces vary in their configuration, but all share the opportunity to self-reflect and to experience emotional validation, normalization, and reality testing from peers or mentors. In mental health training, clinical supervision is one common format for creating such a space. While this can be replicated in the palliative care setting, other strategies include integrating a psychological orientation into interdisciplinary team meetings, creating peer support or process groups, and creating small groups within teams for longitudinal self-reflection.

Innovation in a Crisis: Lessons Learned from the Rapid Development of an End-of-Life Palliative Care Unit during the COVID-19 Pandemic.

COVID-19 strained our nation's hospitals and exposed gaps in care. As COVID-19 surged in Boston in March 2020, we worked to rapidly create a Palliative Care Compassion Unit (PCCU) to care for those dying of COVID-19 or non-COVID-19-related illnesses. The PCCU provided interdisciplinary end-of-life care, supported families, and enabled surge teams to focus on patients needing life-sustaining treatments. In this study, we describe the creation of the PCCU, including opportunities and challenges, in hopes of lending insight to other palliative care teams who may need to rapidly craft new care models during a crisis.

Rectus femoris hyperreflexia contributes to Stiff-Knee gait after stroke.

BACKGROUND: Stiff-Knee gait (SKG) after stroke is often accompanied by decreased knee flexion angle during the swing phase. The decreased knee flexion has been hypothesized to originate from excessive quadriceps activation. However, it is unclear whether hyperreflexia plays a role in this activation. The goal of this study was to establish the relationship between quadriceps hyperreflexia and knee flexion angle during walking in post-stroke SKG. METHODS: The rectus femoris (RF) H-reflex was recorded in 10 participants with post-stroke SKG and 10 healthy controls during standing and walking at the pre-swing phase. In order to attribute the pathological neuromodulation to quadriceps muscle hyperreflexia and activation, healthy individuals voluntarily increased quadriceps activity using electromyographic (EMG) feedback during standing and pre-swing upon RF H-reflex elicitation. RESULTS: We observed a negative correlation (R = - 0.92, p = 0.001) between knee flexion angle and RF H-reflex amplitude in post-stroke SKG. In contrast, H-reflex amplitude in healthy individuals in presence (R = 0.47, p = 0.23) or absence (R = - 0.17, p = 0.46) of increased RF muscle activity was not correlated with knee flexion angle. We observed a body position-dependent RF H-reflex modulation between standing and walking in healthy individuals with voluntarily increased RF activity (d = 2.86, p = 0.007), but such modulation was absent post-stroke (d = 0.73, p = 0.296). CONCLUSIONS: RF reflex modulation is impaired in post-stroke SKG. The strong correlation between RF hyperreflexia and knee flexion angle indicates a possible regulatory role of spinal reflex excitability in post-stroke SKG. Interventions targeting quadriceps hyperreflexia could help elucidate the causal role of hyperreflexia on knee joint function in post-stroke SKG.

Looking Back, and Ahead: A Call to Action for Increasing the Hospice and Palliative Medicine Specialty Pipeline.

Thanks to the efforts of many individuals and organizations, the field of Hospice and Palliative Medicine (HPM) has undergone unprecedented growth over the last two decades. To meet the needs of seriously ill patients and families in inpatient, outpatient community setting in the future, the field of HPM must develop innovative strategies to expand the specialist workforce pipeline. With 148 programs participating in the National Residency Matching Program and 285 matched applicants in 2019, the specialty of HPM can barely replace those who are retiring or leaving the field. We call for a renewed and coordinated effort to increase the applicant pool for HPM fellowship positions, as well as greater access to specialist HPM training through expanded traditional fellowship programs and innovative specialist training pathways. Without such an expansion, our specialty will struggle to serve those patients and families who need us most.

Nipple malposition after bilateral nipple-sparing mastectomy with implant-based reconstruction: Objective postoperative analysis utilizing BCCT.core computer software.

Nipple-sparing mastectomies (NSMs) are accepted as safe oncologic procedures for select patient populations, but objective evaluation of aesthetic outcomes has not been clearly established. The purpose of this study was to utilize BCCT.core computer software to objectively evaluate NAC malposition following bilateral NSM with implant reconstruction and compare the analysis to an expert panel. Postoperative photographs of 43 patients who underwent bilateral NSM were analyzed with the BCCT.core and by an expert panel of plastic surgery residents and attendings. The panel was asked to only evaluate nipple asymmetry and position. The intraclass correlation coefficient (ICC) was used to determine interrater reliability (n = 12) and between expert panel ratings and BCCT.core ratings. Statistics were performed using SPSS statistical package version 24.0. The ICC for the expert panel interrater reliability was excellent (ICC = 0.941, 95% CI: 0.912-0.964). The analysis between BCCT.core individual parameters, specifically the breast retraction assessment (ie, BRA score = the difference in nipple position between the two breasts assessing breast symmetry) and expert panel, showed statistically significant positive correlation. The parameters provided by the BCCT.core software were correlated with both the mean expert panel rating and BCCT.core ratings. Therefore, it is plausible that BCCT.core parameters could be used to objectively quantify NAC malposition/asymmetry and guide treatment in patients undergoing bilateral NSM with implant reconstruction.

Emergence and Containment of Canine Influenza Virus A(H3N2), Ontario, Canada, 2017-2018.

Canine influenza virus (CIV) A(H3N2) was identified in 104 dogs in Ontario, Canada, during December 28, 2017-October 30, 2018, in distinct epidemiologic clusters. High morbidity rates occurred within groups of dogs, and kennels and a veterinary clinic were identified as foci of infection. Death attributable to CIV infection occurred in 2 (2%) of 104 diagnosed cases. A combination of testing of suspected cases, contact tracing and testing, and 28-day isolation of infected dogs was used, and CIV transmission was contained in each outbreak. Dogs recently imported from Asia were implicated as the source of infection. CIV H3N2 spread rapidly within groups in this immunologically naive population; however, containment measures were apparently effective, demonstrating the potential value of prompt diagnosis and implementation of CIV control measures.

Palliative Care-Related Knowledge, Attitudes, and Self-Assessment Among Physicians in Vietnam.

CONTEXT: Palliative care is rarely accessible in low- and middle-income countries, and lack of adequate training for health care providers is a key reason. In Vietnam, the Ministry of Health, major hospitals and medical universities, and foreign physician-educators have partnered to initiate palliative care training for physicians. OBJECTIVES: To measure the baseline palliative care-related knowledge, attitudes, and self-assessment of Vietnamese physicians as a basis for curriculum development and to enable evaluation of training courses. METHODS: Before palliative care training courses in Vietnam from 2007 to 2014, we collected data on the participating physicians' demographics, self-assessed competence in palliative care, and palliative care-related knowledge and attitudes. Scores were calculated in three outcome categories-knowledge, attitudes, and self-assessment-and in two subcategories related to physical and psychological symptoms. Associations between the demographic, education, and practice factors and these scores were assessed using linear regression. RESULTS: Among the 392 physicians surveyed, concern about untreated suffering was highly prevalent. 85% felt that most patients with cancer in Vietnam die in pain. On self-assessment, only 8% felt adequately trained in palliative care and the mean knowledge assessment score was 44%. Although 77% had prescribed an opioid in the past year and most had appropriate attitudes toward the use of morphine for pain, the majority reported explicit or implicit restrictions on prescribing morphine. CONCLUSION: There is a great need among Vietnam's physicians for training in palliative care and especially in nonpain and psychological symptom control. Rational, balanced, and clear opioid-prescribing policies are needed to enable physicians to treat pain without fear of repercussions.

Palliative Care in Vietnam: Long-Term Partnerships Yield Increasing Access.

Palliative care began in Vietnam in 2001, but steady growth in palliative care services and education commenced several years later when partnerships for ongoing training and technical assistance by committed experts were created with the Ministry of Health, major public hospitals, and medical universities. An empirical analysis of palliative care need by the Ministry of Health in 2006 was followed by national palliative care clinical guidelines, initiation of clinical training for physicians and nurses, and revision of opioid prescribing regulations. As advanced and specialist training programs in palliative care became available, graduates of these programs began helping to establish palliative care services in their hospitals. However, community-based palliative care is not covered by government health insurance and thus is almost completely unavailable. Work is underway to test the hypothesis that insurance coverage of palliative home care not only can improve patient outcomes but also provide financial risk protection for patients' families and reduce costs for the health care system by decreasing hospital admissions near the end of life. A national palliative care policy and strategic plan are needed to maintain progress toward universally accessible cost-effective palliative care services.

A Novel Use of Peer Coaching to Teach Primary Palliative Care Skills: Coaching Consultation.

BACKGROUND: We aim to address palliative care workforce shortages by teaching clinicians how to provide primary palliative care through peer coaching. INTERVENTION: We offered peer coaching to internal medicine residents and hospitalists (attendings, nurse practioners, and physician assistants). MEASURES: An audit of peer coaching encounters and coachee feedback to better understand the applicability of peer coaching in the inpatient setting to teach primary palliative care. OUTCOMES: Residents and hospitalist attendings participated in peer coaching for a broad range of palliative care-related questions about pain and symptom management (44%), communication (34%), and hospice (22%). Clinicians billed for 68% of encounters using a time-based billing model. Content analysis of coachee feedback identified that the most useful elements of coaching are easy access to expertise, tailored teaching, and being in partnership. CONCLUSION/LESSONS LEARNED: Peer coaching can be provided in the inpatient setting to teach primary palliative care and potentially extend the palliative care work force.