Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair.

BackgroundPatient‐reported outcomes (PROs) allow for the direct measurement of functional and psychosocial effects related to treatment. However, technological barriers, survey fatigue, and clinician adoption have hindered the meaningful integration of PROs into clinical care. The objective of the authors was to develop an electronic PROs (ePROs) program that meets a range of clinical needs across a head and neck multidisciplinary disease management team.MethodsThe authors developed the ePROs module using literature review and stakeholder input in collaboration with health informatics. They designed an ePROs platform that was integrated as the standard of care for personalized survey delivery by diagnosis across the disease management team. Tableau software was used to create dashboards for data visualization and monitoring at the clinical enterprise, disease subsite, and patient levels. All patients who were treated for head and neck cancer were eligible for ePROs assessment as part of the standard of care. A descriptive analysis of ePROs program implementation is presented herein.ResultsThe Head and Neck Service at Memorial Sloan Kettering Cancer Center has integrated ePROs into clinical care. Surveys are delivered via the patient portal at the time of diagnosis and longitudinally through care. From August 1, 2018, to February 1, 2020, a total of 4154 patients completed ePROs surveys. The average patient participation rate was 69%, with a median time for completion of 5 minutes.ConclusionsIntegration of the head and neck ePROs program as part of clinical care is feasible and could be used to assess value and counsel patients in the future. Continued qualitative assessments of stakeholders and workflow will refine content and enhance the health informatics platform.Lay Summary Patients with head and neck cancer experience significant changes in their quality of life after treatment. Measuring and integrating patient‐reported outcomes as a part of clinical care have been challenging given the multimodal treatment options, vast subsites, and unique domains affected. The authors present a case study of the successful integration of electronic patient‐reported outcomes into a high‐volume head and neck cancer practice.

Physiological disturbances, including temporary hypoxia, are expected to drive angiogenesis during bone repair. Evidence suggests that the angiogenic ligand vascular endothelial growth factor (VEGF)-A plays an important role in this process. We characterized the expression of two receptors that are essential for mediating VEGF signaling, VEGFR1/Flt-1 and VEGFR2/Flk-1/KDR, in a mouse rib fracture model. Their mRNA and protein levels were assessed in four healing phases, which were characterized histologically as hemorrhage formation on postfracture day (PFD) 1, inflammatory response on PFD 3, initiation of callus development on PFD 7, and the presence of a mature callus on PFD 14. Transcript was detected for VEGFR1 and VEGFR2, as well as VEGF. While mRNA expression of VEGFR1 was monophasic throughout all healing phases, VEGFR2 showed a biphasic profile with significantly increased mRNA expression during callus formation and maturation. Expression of VEGF mRNA was characterized by a more gradual increase during callus formation. The protein level for VEGFR1 was below detection sensitivity during the initial healing phase. It was then restored to a stable level, detectable through the subsequent healing phases. Hence, the VEGFR1 protein levels partially mirrored the transcript expression profile. In comparison, the protein level of VEGFR2 increased gradually during the healing phases and peaked at callus maturation. This correlated well with the transcriptional expression of VEGFR2. Intact bone from age-matched male mice had considerable protein levels of VEGFR1 and VEGF, but no detectable VEGFR2. Together, these findings uncovered expression signatures of the VEGF-VEGFR axis in endochondral bone repair.

PURPOSE: Oncology patients are vulnerable to adverse outcomes associated with COVID-19, and clinical deterioration must be identified early. Several institutions launched remote patient monitoring programs (RPMPs) to care for patients with COVID-19. We describe patients' perspectives on a COVID-19 RPMP at a National Comprehensive Cancer Center. METHODS: Patients who tested positive for COVID-19 were eligible. Enrolled patients received a daily electronic COVID-19 symptom assessment, and a subset of high-risk patients also received a pulse oximeter. Monitoring was provided by a centralized team and was discontinued 14 days after a patient's positive test result and following 3 days without worsening symptoms. Patients who completed at least one assessment and exited the program were sent a patient engagement survey to evaluate the patient's experience with digital monitoring for COVID-19. RESULTS: The survey was distributed to 491 patients, and 257 responded (52% completion rate). The net promoter score was 85%. Most patients agreed that the RPMP was worthwhile, enabled better management of their COVID-19 symptoms, made them feel more connected to their healthcare team, and helped prevent emergency room visits. Identified themes regarding patient-perceived value of a RPMP included (1) security: a clinical safety net; (2) connection: a link to their clinical team during a period of isolation; and (3) empowerment: an education on the virus and symptom management. CONCLUSION: RPMPs are perceived to be of value to oncology patients with COVID-19. Policymakers should consider how these programs can be reimbursed to keep vulnerable patients at home and out of the acute care setting.