Development of an integrated milestone assessment tool across multiple early-adopter programs for breaking bad news: a pilot project.

BACKGROUND: The transition of the Accreditation Council for Graduate Medical Education (ACGME) to milestone assessment creates opportunities for collaboration and shared assessments across graduate medical programs. Breaking bad news is an essential communication skill that is a common milestone across almost every medical specialty. The purpose of this study was to develop and pilot an integrated milestone assessment (IMA) tool for breaking bad news using ACGME milestone criteria and to compare the IMA tool with the existing SPIKES protocol. METHODS: The IMA tool was created using sub-anchors in professionalism and interpersonal communication skills that are applicable to every specialty and to the ability to break bad news. Two cases of breaking bad news, designed to be "easy" and "intermediate" in difficulty, were used to assess basic skills in breaking bad news in first-year medical residents from six residency specialties. Eight standardized patients were trained to portray the cases in sessions held in November 2013 and May 2014. Standardized patients completed an assessment checklist to evaluate each resident's performance in breaking bad news based on their use of the SPIKES protocol and IMA tool. Residents answered post-encounter questions about their training and comfort in breaking bad news. The association between SPIKES and IMA scores was investigated by simple linear regression models and Spearman rank correlations. RESULTS: There were 136 eligible medical residents: 108 (79.4%) participated in the first session and 97 (71.3%) participated in the second session, with 96 (70.6%) residents participating in both sessions. Overall, we were able to identify residents that performed at both extremes of the assessment criteria using the integrated milestone assessment (IMA) and the SPIKES protocol. Interestingly, residents rated themselves below "comfortable" on average. CONCLUSION: We developed an integrated milestone assessment (IMA) that was better than the SPIKES protocol at assessing the skill of breaking bad news. This collaborative assessment tool can be used as supplement tool in the era of milestone transformation. We aim assess our tool in other specialties and institutions, as well as assess other shared milestones across specialties.

Tumor-specific polycistronic miRNA delivered by engineered exosomes for the treatment of glioblastoma.

BACKGROUND: Glioblastoma (GBM) has poor prognosis due to ineffective agents and poor delivery methods. MicroRNAs (miRs) have been explored as novel therapeutics for GBM, but the optimal miRs and the ideal delivery strategy remain unresolved. In this study, we sought to identify the most effective pan-subtype anti-GBM miRs and to develop an improved delivery system for these miRs. METHODS: We conducted an unbiased screen of over 600 miRs against 7 glioma stem cell (GSC) lines representing all GBM subtypes to identify a set of pan-subtype-specific anti-GBM miRs and then used available TCGA GBM patient outcomes and miR expression data to hone in on miRs that were most likely to be clinically effective. To enhance delivery and expression of the miRs, we generated a polycistronic plasmid encoding 3 miRs (pPolymiR) and used HEK293T cells as biofactories to package pPolymiR into engineered exosomes (eExos) that incorporate viral proteins (Gag/VSVg) in their structure (eExos+pPolymiR) to enhance function. RESULTS: Our stepwise screen identified miR-124-2, miR-135a-2, and let-7i as the most effective miRs across all GBM subtypes with clinical relevance. Delivery of eExos+pPolymiR resulted in high expression of all 3 miRs in GSCs, and significantly decreased GSC proliferation in vitro. eExos+pPolymiR prolonged survival of GSC-bearing mice in vivo when compared with eExos carrying each of the miRs individually or as a cocktail. CONCLUSION: eExos+pPolymiR, which includes a pan-subtype anti-glioma-specific miR combination encoded in a polycistronic plasmid and a novel exosome delivery platform, represents a new and potentially powerful anti-GBM therapeutic.

Clinical outcomes of stereotactic biopsy on children with pontine diffuse midline glioma.

INTRODUCTION: Diffuse midline glioma (DMG) of the pons occurs in pediatric patients and carries a dismal prognosis. Biopsy is not necessary for diagnosis but provides information, particularly H3K27M status, with prognostic implications. Additionally, biopsy information may open therapeutic options such as clinical trials that require mutation status. Therefore, we sought to assess the safety of surgical biopsy in DMG patients as well as its potential impact on clinical course. METHODS: Retrospective analysis of patients who were radiographically and clinically diagnosed with pontine DMG in the last 5 years was performed. We assessed demographic, clinical, radiographic, surgical, and follow-up data. RESULTS: 25 patients were included; 18 (72%) underwent biopsy while 7 (28%) declined. 12 biopsies (67%) were performed with robotic arm and 5 (27%) with frameless stereotaxy. Three biopsied patients (17%) experienced new post-operative neurologic deficits (1 facial palsy, 1 VI nerve palsy and 1 ataxia) that all resolved at 2-week follow-up. All biopsies yielded diagnostic tissue. Fourteen patients (78%) had H3K27M mutation. Median OS for H3K27M patients was 10 months compared to 11 months in the wild-type patients (p = 0.30, log-rank test). Median OS for patients enrolled in clinical trials was 12 months compared to 8 months for non-trial patients (p = 0.076). CONCLUSION: In our series, stereotactic pontine DMG biopsies did not carry any permanent deficit or complication and yielded diagnostic tissue in all patients. Similar post-operative course was observed in both robot-assisted and frameless stereotactic approaches. There was no significant difference in survival based on mutation status or clinical trial enrollment.

Varied histomorphology and clinical outcomes of FGFR3-TACC3 fusion gliomas.

Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.

Recurrent HGNET-MN1 altered (astroblastoma MN1-altered) of the foramen magnum: Case report and molecular classification.

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity. Case Description: Here, we present the case of a 36-year-old right-handed woman with recurrent low-grade astroblastoma in the cervicomedullary junction. The patient presented with worsening motor and sensory deficits of her upper extremities, pain, ataxia, visual disturbance, and nausea. Due to extensive recurrence and neurological symptoms, the patient underwent reoperation. Conclusion: We review a rare case of recurrent astroblastoma in the foramen magnum in light of new relevant literature about tumor biology and prognostic significance of the new classification of astroblastoma MN1-altered.

3-Dimensional Modeling in Virtual Reality for Resection of a Pineal Region Falcotentorial Meningioma.

We present a parietal interhemispheric approach to resect a pineal region falcotentorial meningioma. Three-dimensional (3D) modeling was used to visualize and plan the surgical approach in virtual reality (Video 1). A 78-year-old woman was incidentally found to have a slow-growing falcotentorial meningioma. The tumor was first treated with stereotactic radiosurgery, but the patient had progressive confusion, memory issues, and bilateral temporal field cuts with interval expansion of the tumor and significantly increased peritumoral vasogenic edema on magnetic resonance imaging. After recommending tumor resection, the patient consented to surgery and underwent resection via a posterior interhemispheric subsplenial approach. Using a 3D model in virtual reality, we discuss the advantages and disadvantages of various classical approaches to the pineal region for resection of this tumor.1-3 Falcotentorial meningiomas often displace the deep veins inferiorly, making an interhemispheric approach more favorable.4-6 Preoperative visualization of critical deep venous structures with the 3D model was a valuable adjunct to magnetic resonance imaging for achieving safe resection. We depict key steps of the surgical planning process using virtual reality and demonstrate how simulation can be used to evaluate risks and benefits of different surgical corridors. A small rim of residual tumor adherent to the deep cerebral veins was intentionally left behind in order to minimize risk of morbidity to the patient.7 At 1-month follow-up, the patient's cognition had returned to baseline and her vision had significantly improved. Ultimately, surgical planning using virtual reality promotes both neurosurgical education and patient safety through clear visualization and understanding of different surgical approaches.

Foramen Magnum Dural Arteriovenous Fistula Presenting With Thoracic Myelopathy: Technical Case Report With 2-Dimensional Operative Video.

BACKGROUND AND IMPORTANCE: Dural arteriovenous fistulas (dAVFs) are vascular abnormalities of the central nervous system that can cause a wide array of neurological dysfunction depending on their location, flow, and propensity to rupture. Symptomatic dAVFs at the cranio-cervical junction usually result in hemorrhage or cervical myelopathy. Distantly located dAVFs of the foramen magnum are a rare cause of thoracic intrinsic myelopathy. CLINICAL PRESENTATION: An 83-yr-old man presented with progressive lower extremity weakness, numbness, and difficulty walking along with episodes of bowel incontinence. Magnetic resonance imaging of the cervical spine demonstrated multilevel cervical disc disease with stenosis and longitudinal cervical cord signal change extending into the upper thoracic spinal cord. Cerebral and spinal angiography revealed a dAVF in the lateral foramen magnum region. Given the location, feeding vasculature, and morphology of the fistula, endovascular embolization was not attempted. Microsurgical resection with confirmative indocyanine green fluorescent imaging was performed with adequate obliteration of the fistula. The patient's neurological baseline was preserved postoperatively with improvement of lower extremity numbness. CONCLUSION: We present a brief overview of this neuropathologic entity and demonstrate microsurgical resection of a foramen magnum dAVF through operative video. Craniocervical dAVFs should remain on the differential diagnosis of patients presenting with progressive thoracolumbar myelopathy.

Intracranial Solitary Fibrous Tumor of the Skull Base: 2 Cases and Systematic Review of the Literature.

BACKGROUND: Intracranial solitary fibrous tumors (ISFTs) are rare neoplasms of mesenchymal origin that originate from the meninges. ISFTs of the skull base can be challenging to treat, as resection can be complicated by skull base anatomy. We present 2 cases of ISFT, the first manifesting with compressive cranial neuropathy from Meckel cave involvement and the second a posterior fossa lesion causing symptomatic hydrocephalus. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed database was queried with title/abstract keywords "intracranial," "solitary fibrous tumor," "hemangiopericytoma," "SFT," and "HPC." Search results were reviewed to exclude cases not involving the skull base. References from all selected articles were reviewed for potential additional cases. Patient demographic and clinical data from 58 identified skull base cases were collected for qualitative synthesis. RESULTS: Visual disturbances were the most common presenting symptom (30 cases, 52%) followed by headache (22 cases, 38%). The most common site of involvement was the sellar/parasellar region (18 cases, 31%) followed by middle fossa/temporal bone (14 cases, 24%). Resection was performed in 55 cases; gross total resection was reported in 26 cases (45%) and subtotal resection was reported in 21 cases (36%). Tumor recurrence was documented in 15 cases (26%) with median and mean follow-up periods of 16 and 29.9 months, respectively. CONCLUSIONS: We discuss presentation, imaging, histopathology, and management considerations for ISFTs while highlighting the potentially complex nature of skull base lesions and need for multidisciplinary approach to treatment.

Fully Endoscopic Resection of an Epidermoid Cyst of the Cerebellopontine Angle: Bilateral Resection via a Unilateral Approach.

BACKGROUND AND IMPORTANCE: Epidermoid cysts are rare, benign intracranial neoplasms that typically arise at the cerebellopontine angle (CPA) and can be extensive lesions that intricately involve many critical neurovascular structures. We describe the case of a patient who presents with the classic picture of CPA epidermoid cyst and describe the value of the 4K endoscope for resection, which is illustrated in our accompanying surgical video. CLINICAL PRESENTATION: The patient presents with headache, nausea, and vomiting accompanied by dizziness and balance issues. Radiographic imaging demonstrated a large lesion highly consistent with epidermoid cyst which involved the left CPA, encircled the basilar artery, and extended to the opposite side. Surgery was planned with a small left-sided retrosigmoid craniotomy with use of a 2-dimensional 4K endoscope to aid in resection, particularly of the contralateral side. This approach was successful with gross total resection apparent at 14-mo follow-up. CONCLUSION: We describe the use of a fully endoscopic technique from a unilateral approach for resection of a lesion that extended in the CPA bilaterally. Additionally, we highlight the relevant neuroanatomical and neurovascular structures in this highly critical intracranial region which is well-visualized through endoscopy in the associated surgical video.

Intraspinal mesenchymal chondrosarcoma: An argument for aggressive local resection and adjuvant therapy based on review of the literature.

BACKGROUND: Mesenchymal chondrosarcoma is a rare cartilaginous neoplasm that typically involves the axial skeleton. Despite a well-circumscribed appearance, this tumor has a tendency to recur both locally and with distant metastases. CASE DESCRIPTION: A 17-year-old patient presented with numbness and paresthesias in the lower extremities attributed to a T10-T11 intradural extramedullary mesenchymal chondrosarcoma. The patient was treated with aggressive local resection and adjuvant therapy. Here, this case and present literature are appropriately reviewed. CONCLUSION: Although uncommon, intraspinal mesenchymal chondrosarcomas warrant both radical local resection and aggressive adjuvant therapy with chemoradiation to provide the greatest chance of progression-free survival.

Spinal meningioma in a patient with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is the most common immune-mediated inflammatory demyelinating disease of the central nervous system. Multiple brain and spinal tumors have been linked to MS, but a causal relationship between the two has not been determined. Here, we report a case of spinal meningioma in a patient with MS and review literature discussing the possible connection between these two disease entities. CASE DESCRIPTION: A 58-year-old female with MS presented with a 1-year history of progressively worsening back pain in conjunction with worsening right upper and lower extremity weakness. The patient was diagnosed with MS 19 months prior and had multiple known demyelinating plaques in her cervical spine. New MRI revealed an intradural extramedullary thoracic tumor with characteristics consistent with meningioma. She underwent T6- T8 laminectomies for tumor resection and pathology confirmed the radiological diagnosis. At 3-month follow- up, the patient reported complete resolution of her back pain and persistence of weakness-related gait issues. CONCLUSION: CNS neoplasms including meningioma should be considered in MS patients presenting with newly onset neurological symptoms not entirely consistent with demyelinating disease. Both disease processes should be addressed with appropriate long-term follow-up.

Neurenteric Cyst: Case Report and Operative Video.

Neurenteric cysts are rare, congenital lesions of the spinal axis composed of endodermal tissue arising from poor segmentation of the notochord. A 36-year-old patient presented with arm paresthesias and incontinence with imaging revealing a lesion in the C6-C7 region most consistent with neurenteric cyst. After partial resection of the lesion, the patient regained all neurological function. Here, we provide a brief overview of this rare neuropathologic entity and demonstrate surgical resection of neurenteric cyst through operative video.

Glioblastoma multiforme: novel therapeutic targets.

INTRODUCTION: The increasingly detailed genetic characterization of glioblastoma (GBM) has failed to translate into meaningful breakthroughs in treatment. This is likely to be attributed to molecular heterogeneity of GBM. However, the understanding of the tumor microenvironment in GBM has become more refined and has revealed a wealth of therapeutic targets that may enable the disruption of angiogenesis or immunosuppression. AREAS COVERED: This review discusses the selective targeting of tumor-intrinsic pathways, therapies that target the GBM tumor microenvironment and relevant preclinical studies and their limitations. Relevant literature was derived from a PubMed search encompassing studies from 1989 to 2020. EXPERT OPINION: Despite appropriate target engagement, attempts to directly inhibit oncogenic pathways in GBM have yielded little success. This is likely attributed to the molecular heterogeneity of GBM and the presence of redundant signaling that allow for accumulation of adaptive mutations and development of drug resistance. Subsequently, there has been a shift toward therapies modulating the pro-angiogenic, immunosuppressive tumor microenvironment in GBM. The non-transformed cells in the microenvironment which includes endothelial cells, myeloid cells, and T cells, are presumably genetically stable, less susceptible to heterogeneity, and easier to target. This approach offers the highest potential for a therapeutic breakthrough in GBM.

Cervical Intradural Disc Herniation: Case Report and Operative Video.

Cervical intradural disc herniation (CIDH) is a rare presentation of an intradural disc herniation. We present a case of CIDH with associated surgical video depicting an anterior surgical approach to treatment. Patient presentation, relevant radiographic imaging, surgical exposure and technique, and cerebrospinal fluid leak complication and prevention are discussed.

Predictive factors of incomplete aneurysm occlusion after endovascular treatment with the Pipeline embolization device.

OBJECTIVE: The Pipeline embolization device (PED) is a routine choice for the endovascular treatment of select intracranial aneurysms. Its success is based on the high rates of aneurysm occlusion, followed by near-zero recanalization probability once occlusion has occurred. Therefore, identification of patient factors predictive of incomplete occlusion on the last angiographic follow-up is critical to its success. METHODS: A multicenter retrospective cohort analysis was conducted on consecutive patients treated with a PED for unruptured aneurysms in 3 academic institutions in the US. Patients with angiographic follow-up were selected to identify the factors associated with incomplete occlusion. RESULTS: Among all 3 participating institutions a total of 523 PED placement procedures were identified. There were 284 procedures for 316 aneurysms, which had radiographic follow-up and were included in this analysis (median age 58 years; female-to-male ratio 4.2:1). Complete occlusion (100% occlusion) was noted in 76.6% of aneurysms, whereas incomplete occlusion (≤ 99% occlusion) at last follow-up was identified in 23.4%. After accounting for factor collinearity and confounding, multivariable analysis identified older age (> 70 years; OR 4.46, 95% CI 2.30-8.65, p < 0.001); higher maximal diameter (≥ 15 mm; OR 3.29, 95% CI 1.43-7.55, p = 0.005); and fusiform morphology (OR 2.89, 95% CI 1.06-7.85, p = 0.038) to be independently associated with higher rates of incomplete occlusion at last follow-up. Thromboembolic complications were noted in 1.4% and hemorrhagic complications were found in 0.7% of procedures. CONCLUSIONS: Incomplete aneurysm occlusion following placement of a PED was independently associated with age > 70 years, aneurysm diameter ≥ 15 mm, and fusiform morphology. Such predictive factors can be used to guide individualized treatment selection and counseling in patients undergoing cerebrovascular neurosurgery.

Adoption of Information and Communication Technologies for Early Detection of Breast and Cervical Cancers in Low- and Middle-Income Countries.

PURPOSE: In response to the growing burden of breast and cervical cancers, low- and middle-income countries (LMICs) are beginning to implement national cancer prevention programs. We reviewed the literature on information and communication technology (ICT) applications in the prevention of breast and cervical cancers in LMICs to examine their potential to enhance cancer prevention efforts. METHODS: Ten databases of peer-reviewed and gray literature were searched using an automated strategy for English-language articles on the use of mobile health (mHealth) and telemedicine in breast and cervical cancer prevention (screening and early detection) published between 2005 and 2015. Articles that described the rationale for using these ICTs and/or implementation experiences (successes, challenges, and outcomes) were reviewed. Bibliographies of articles that matched the eligibility criteria were reviewed to identify additional relevant references. RESULTS: Of the initial 285 citations identified, eight met the inclusion criteria. Of these, four used primary data, two were overviews of ICT applications, and two were commentaries. Articles described the potential for mHealth and telemedicine to address both demand- and supply-side challenges to cancer prevention, such as awareness, access, and cost, in LMICs. However, there was a dearth of evidence to support these hypotheses. CONCLUSION: This review indicates that there are few publications that reflect specifically on the role of mHealth and telemedicine in cancer prevention and even fewer that describe or evaluate interventions. Although articles suggest that mHealth and telemedicine can enhance the implementation and use of cancer prevention interventions, more evidence is needed.