Flourishing at the end of life.

Flourishing is an increasingly common construct employed in the study of human wellbeing. But its appropriateness as a framework of wellbeing at certain stages of life is contested. In this paper, we consider to what extent it is possible for someone to flourish at the end of life. People with terminal illness often experience significant and protracted pain and suffering especially when they opt for treatments that prolong life. Certain aspects of human goods, however, that are plausibly constitutive of flourishing-such as meaning and purpose, deep personal relationships, and character and virtue-can be uniquely realised when life is ending. We argue that there is a qualified sense in which one can flourish at the end of life but that one must make important modifications to the criteria implicit in conventional conceptions of flourishing. We close with a discussion of the empirical assessment of wellbeing at the end of life and explore the possibility of introducing a flourishing measure in palliative care practice.

Altered Mental Status in Cancer.

Patients with cancer experience high rates of alterations in mental status. The mechanisms for altered mental status (AMS) in this population are manifold. The cancer itself may cause AMS through direct invasion of the central nervous system or as metastatic leptomeningeal spread. However, cancer patients are also vulnerable to tumor-associated complications such as seizures, cerebral edema, strokes, or cancer treatment-related complications such as infections, direct neural injury from radiation or chemotherapy, edema, or dysregulated autoimmune response from immunotherapies. Both during treatment and as sequelae, patients may suffer neurocognitive complications from chemotherapy and radiation, medications or opportunistic infections, as well as toxic-metabolic, nutritional, and endocrine complications. In this review, we describe a clinical approach to the cancer patient presenting with AMS and discuss the differential drivers of AMS in this patient population. While common etiologies of AMS in noncancer patients (toxic-metabolic or infectious encephalopathy, delirium) are also applicable to cancer patients, we additionally provide a cancer-specific differential diagnosis that warrants special consideration in the cancer patient with AMS.

Contemporary Practice Patterns in the Treatment of Cervical Stenosis and Central Cord Syndrome: A Survey of the Cervical Spine Research Society.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To evaluate for areas of consensus and divergence of opinion within the spine community regarding the management of cervical spondylotic conditions and acute traumatic central cord syndrome (ATCCS) and the influence of the patient's age, disease severity, and myelomalacia. SUMMARY OF BACKGROUND DATA: There is ongoing disagreement regarding the indications for, and urgency of, operative intervention in patients with mild degenerative myelopathy, moderate to severe radiculopathy, isolated axial symptomatology with evidence of spinal cord compression, and ATCCS without myelomalacia. METHODS: A survey request was sent to 330 attendees of the Cervical Spine Research Society (CSRS) 2021 Annual Meeting to assess practice patterns regarding the treatment of cervical stenosis, myelopathy, radiculopathy, and ATCCS in 16 unique clinical vignettes with associated MRIs. Operative versus nonoperative treatment consensus was defined by a management option selected by >80% of survey participants. RESULTS: Overall, 116 meeting attendees completed the survey. Consensus supported nonoperative management for elderly patients with axial neck pain and adults with axial neck pain without myelomalacia. Operative management was indicated for adult patients with mild myelopathy and myelomalacia, adult patients with severe radiculopathy, elderly patients with severe radiculopathy and myelomalacia, and elderly ATCCS patients with pre-existing myelopathic symptoms. Treatment discrepancy in favor of nonoperative management was found for adult patients with isolated axial symptomatology and myelomalacia. Treatment discrepancy favored operative management for elderly patients with mild myelopathy, adult patients with mild myelopathy without myelomalacia, elderly patients with severe radiculopathy without myelomalacia, and elderly ATCCS patients without preceding symptoms. CONCLUSIONS: Although there is uncertainty regarding the treatment of mild myelopathy, operative intervention was favored for nonelderly patients with evidence of myelomalacia or radiculopathy and for elderly patients with ATCCS, especially if pre-injury myelopathic symptoms were present. LEVEL OF EVIDENCE: Level V.

The utility of intraoperative ultrasonography for spinal cord surgery.

OBJECTIVES: Intraoperative ultrasonography (IOUS) offers the advantage of providing real-time imaging features, yet it is not generally used. This study aims to discuss the benefits of utilizing IOUS in spinal cord surgery and review related literature. MATERIALS AND METHODS: Patients who underwent spinal cord surgery utilizing IOUS at a single institution were retrospectively collected and analyzed to evaluate the benefits derived from the use of IOUS. RESULTS: A total of 43 consecutive patients were analyzed. Schwannoma was the most common tumor (35%), followed by cavernous angioma (23%) and ependymoma (16%). IOUS confirmed tumor extent and location before dura opening in 42 patients (97.7%). It was particularly helpful for myelotomy in deep-seated intramedullary lesions to minimize neural injury in 13 patients (31.0% of 42 patients). IOUS also detected residual or hidden lesions in 3 patients (7.0%) and verified the absence of hematoma post-tumor removal in 23 patients (53.5%). In 3 patients (7.0%), confirming no intradural lesions after removing extradural tumors avoided additional dural incisions. IOUS identified surrounding blood vessels and detected dural defects in one patient (2.3%) respectively. CONCLUSIONS: The IOUS can be a valuable tool for spinal cord surgery in identifying the exact location of the pathologic lesions, confirming the completeness of surgery, and minimizing the risk of neural and vascular injury in a real-time fashion.

Surgical Strategy for Dumbbell-Shaped Cervical Schwannoma at the Vicinity of the Vertebral Artery: The Utilization of Anatomic Layer.

BACKGROUND AND OBJECTIVES: In cases where dumbbell-shaped cervical schwannoma encases the vertebral artery (VA), there is a risk of VA injury during surgery. The objective of this study is to propose a strategy for preserving the VA during the surgical excision of tumors adjacent to the VA through the utilization of anatomic layers. METHODS: A retrospective analysis was conducted on 37 patients who underwent surgery for dumbbell-shaped cervical schwannoma with contacting VA from January 2004 to July 2023. The VA encasement group consisted of 12 patients, and the VA nonencasement group included 25 patients. RESULTS: The perineurium acted as a protective barrier from direct VA exposure or injury during surgery. However, in the VA encasement group, 1 patient was unable to preserve the perineurium while removing a tumor adjacent to the VA, resulting in VA injury. The patient had the intact dominant VA on the opposite side, and there were no new neurological deficits or infarctions after the surgery. Gross total resection was achieved in 25 patients (67.6%), while residual tumor was confirmed in 12 patients (32.4%). Four patients (33.3% of 12 patients) underwent reoperation because of the regrowth of the residual tumor within the neural foramen. In the case of the 8 patients (66.7% of 12 patients) whose residual tumor was located outside the neural foramen, no regrowth was observed, and there was no recurrence of the tumor within the remaining perineurium after total resection. CONCLUSION: In conclusion, when resecting a dumbbell-shaped cervical schwannoma contacting VA, subperineurium dissection prevents VA injury because the perineurium acts as a protective barrier.

Wound Healing Complications Associated with Staged Reconstruction after Facial Lentigo Maligna Resection.

Background: The rates and risk factors for wound complications following staged reconstruction after facial lentigo maligna (LM) resection have not been well described. Objectives: (1) To identify the rate and types of wound complications, including infection, graft necrosis, distal flap necrosis, hematoma, superficial epidermolysis, and seroma among patients undergoing staged reconstruction after resection of LM as documented in the surgeon's clinical notes within 30 days of the procedure. (2) To determine a threshold defect size that may predict the development of wound complications. Design and Outcomes: Retrospective review at an academic medical center of patients who underwent staged reconstruction after facial LM resection over a 5-year period. Results: Ninety-eight patients were identified with a mean age of 69.2 ± 13.6 years; 37% of patients were female. The most common defect sites were the cheek (n = 41; 42%) and nose (n = 22; 22%). Twenty-five of 98 patients (26%) demonstrated complications, with the most common being wound infection (36%) and graft necrosis (24%). Those receiving perioperative antibiotics had lower rates of complication (odds ratio [OR]: 0.36; 95% confidence interval [CI]: 0.13,0.96; p = 0.041). Defects greater than 2.7 cm in maximal diameter had the highest sensitivity for predicting complications. Conclusions: Patients undergoing staged reconstruction after facial LM resection have a high rate of wound complication (26%) and defect size > 2.7 cm may be an important risk factor.

Trends in degenerative lumbar spinal surgery during the early COVID-19 pandemic in Republic of Korea: A national study utilizing the national health insurance database.

During the first year of the COVID-19 pandemic, the Republic of Korea (ROK) experienced three epidemic waves in February, August, and November 2020. These waves, combined with the overarching pandemic, significantly influenced trends in spinal surgery. This study aimed to investigate the trends in degenerative lumbar spinal surgery in ROK during the early COVID-19 pandemic, especially in relation to specific epidemic waves. Using the National Health Information Database in ROK, we identified all patients who underwent surgery for degenerative lumbar spinal diseases between January 1, 2019 and December 31, 2020. A joinpoint regression was used to assess temporal trends in spinal surgeries over the first year of the COVID-19 pandemic. The number of surgeries decreased following the first and second epidemic waves (p<0.01 and p = 0.34, respectively), but these were offset by compensatory increases later on (p<0.01 and p = 0.05, respectively). However, the third epidemic wave did not lead to a decrease in surgical volume, and the total number of surgeries remained comparable to the period before the pandemic. When compared to the pre-COVID-19 period, average LOH was reduced by 1 day during the COVID-19 period (p<0.01), while mean hospital costs increased significantly from 3,511 to 4,061 USD (p<0.01). Additionally, the transfer rate and the 30-day readmission rate significantly decreased (both p<0.01), while the reoperation rate remained stable (p = 0.36). Despite the impact of epidemic waves on monthly surgery numbers, a subsequent compensatory increase was observed, indicating that surgical care has adapted to the challenges of the pandemic. This adaptability, along with the stable total number of operations, highlights the potential for healthcare systems to continue elective spine surgery during public health crises with strategic resource allocation and patient triage. Policies should ensure that surgeries for degenerative spinal diseases, particularly those not requiring urgent care but crucial for patient quality of life, are not unnecessarily halted.

Targeting KRAS Oncogene for Patients With Colorectal Cancer: A New Step Toward Precision Medicine.

KRAS mutations are common driver oncogenes associated with the development of several solid tumors. KRAS oncogene has been considered a highly challenging target for drug development because of structural features, including the lack of deep groove on its catalytic unit. However, by leveraging cysteine residues, covalent KRAS inhibitors irreversibly trap KRAS G12C mutants in their inactive GDP-bound state. These agents have resulted in significant clinical responses among patients with KRAS G12C-mutant solid tumors, including patients with colorectal cancer (CRC). Other allele-specific inhibitors of KRAS oncogene and panKRAS and panRAS inhibitors are also currently being investigated in clinical trials. This review article overviews recent clinical progress on KRAS G12C targeting for the management of patients with KRAS G12C-mutant CRC and provides an update on other RAS targeting approaches. We also discuss the unique biological features of RAS-mutant CRC, which require the combination of KRAS inhibitors and anti-epidermal growth factor receptor therapy, and elaborate on resistance mechanisms and novel therapeutic avenues that may define future treatment paradigms of patients with RAS-mutant CRC.

"So we brought these players together": a qualitative study of educators' experiences to analyze the challenges of creating an e-learning program for neuropalliative care.

BACKGROUND: In recent years, the subspecialty of neuropalliative care has emerged with the goal of improving the quality of life of patients suffering from neurological disease, though gaps remain in neuropalliative care education and training. E-learning has been described as a way to deliver interactive and facilitated lower-cost learning to address global gaps in medical care. We describe here the development of a novel, international, hybrid, and asynchronous curriculum with both self-paced modules and class-based lectures on neuropalliative care topics designed for the neurologist interested in palliative care, the palliative care physician interested in caring for neurological patients, and any other physician or advanced care providers interested in neuropalliative care. METHODS: The course consisted of 12 modules, one per every four weeks, beginning July 2022. Each module is based on a case and relevant topics. Course content was divided into three streams (Neurology Basics, Palliative Care Basics, and Neuropalliative Care Essentials) of which two were optional and one was mandatory, and consisted of classroom sessions, webinars, and an in-person skills session. Evaluation of learners consisted of multiple choice questions and written assignments for each module. Evaluation of the course was based on semi-structured qualitative interviews conducted with both educator and learner, the latter of which will be published separately. Audio files were transcribed and underwent thematic analysis. For the discussion of the results, Khan's e-learning framework was used. RESULTS: Ten of the 12 participating educators were interviewed. Of the educators, three identified as mid-career and seven as senior faculty, ranging from six to 33 years of experience. Nine of ten reported an academic affiliation and all reported association with a teaching hospital. Themes identified from the educators' evaluations were: bridging the global gap, getting everybody on board, defining the educational scope, investing extensive hours of voluntary time and resources, benefiting within and beyond the curriculum, understanding the learner's experience, creating a community of shared learning, adapting future teaching and learning strategies, and envisioning long term sustainability. CONCLUSIONS: The first year of a novel, international, hybrid, and asynchronous neuropalliative care curriculum has been completed, and its educators have described both successes and avenues for improvement. Further research is planned to assess this curriculum from the learner perspective.

Clinical and radiologic outcomes of posterior column extension, pedicle subtraction, and vertebral column resection osteotomies in adult chin on chest deformity: A systematic review.

Background: Chin-on-chest deformity is a rare and severely disabling condition characterized by kyphotic deformity in the cervicothoracic spine. To treat this deformity, various osteotomy techniques were described. Methods: A comprehensive literature search of biomedical databases including MEDLINE (via PubMed), Scopus (via Elsevier), Embase (via Elsevier), and Cochrane Library in English from 1/1/1990 to 3/31/2022 was conducted using a combination of text and Medical Subject Headings (MeSH). Results: The final analysis included 16 studies. All the studies were assigned a level of evidence of four. Except for two articles, all of the articles were non-comparative studies. A total of 288 patients were included in this review. Of the 288 patients, 107 underwent posterior column extension osteotomy (PCEO), 108 underwent pedicle subtraction osteotomy (PSO), and 33 underwent vertebral column resection osteotomy (VCRO). The most common osteotomy level in fifteen of the studies was C7/T1. The studies included in this review described several techniques for cervical sagittal balance correction. The range of preoperative and postoperative visual analogue scale (VAS) scores was 5.5-8.6 to 1.7-4.91, respectively. The range of preoperative and postoperative neck disability index (NDI) was 34.2-65.4 to 22.1-51.3, respectively. The most common complications were upper extremity paresthesia and hand numbness through the C8 dermatome distribution. Conclusions: Corrective osteotomies provide satisfactory results in patients with chin-on-chest deformity; however, the quality of the included studies limits the evidence.

Effects of Mucosal Decongestion on Nasal Aerodynamics: A Pilot Study.

OBJECTIVE: Mucosal decongestion with nasal sprays is a common treatment for nasal airway obstruction. However, the impact of mucosal decongestion on nasal aerodynamics and the physiological mechanism of nasal airflow sensation are incompletely understood. The objective of this study is to compare nasal airflow patterns in nasal airway obstruction (NAO) patients with and without mucosal decongestion and nondecongested healthy subjects. STUDY DESIGN: Cross-sectional study of a convenience sample. SETTING: Academic tertiary medical center. METHODS: Forty-five subjects were studied (15 nondecongested healthy subjects, 15 nondecongested NAO patients, and 15 decongested NAO patients). Three-dimensional models of the nasal anatomy were created from computed tomography scans. Steady-state simulations of airflow and heat transfer were conducted at 15 L/min inhalation rate using computational fluid dynamics. RESULTS: In the narrow side of the nose, unilateral nasal resistance was similar in decongested NAO patients and nondecongested healthy subjects, but substantially higher in nondecongested NAO patients. The vertical airflow distribution within the nasal cavity (inferior vs middle vs superior) was also similar in decongested NAO patients and nondecongested healthy subjects, but nondecongested NAO patients had substantially less middle airflow. Mucosal cooling, quantified by the surface area where heat flux exceeds 50 W/m2, was significantly higher in decongested NAO patients than in nondecongested NAO patients. CONCLUSION: This pilot study suggests that mucosal decongestion improves objective measures of nasal airflow, which is consistent with improved subjective sensation of nasal patency after decongestion.

Estimation of Nasal Airway Cross-sectional Area From Endoscopy Using Depth Maps: A Proof-of-Concept Study.

OBJECTIVE: Endoscopy is routinely used to diagnose obstructive airway diseases. Currently, endoscopy is only a visualization technique and does not allow quantification of airspace cross-sectional areas (CSAs). This pilot study tested the hypothesis that CSAs can be accurately estimated from depth maps created from virtual endoscopy videos. STUDY DESIGN: Cross-sectional. SETTING: Academic tertiary medical center. METHODS: Virtual endoscopy and depth map videos of the nasal cavity were digitally created based on anatomically accurate three-dimensional (3D) models built from computed tomography scans of 30 subjects. A software tool was developed to outline the airway perimeter and estimate the airspace CSA from the depth maps. Two otolaryngologists used the software tool to estimate the nasopharynx CSA and the nasal valve minimal CSA (mCSA) in the left and right nasal cavities. Model validation statistics were performed. RESULTS: Nasopharynx CSA had a median percent error of 3.7% to 4.6% when compared to the true values measured in the 3D models. Nasal valve mCSA had a median percent error of 22.7% to 33.6% relative to the true values. Raters successfully used the software tool to identify subjects with nasal valve stenosis (ie, mCSA < 0.20 cm2) with a sensitivity of 83.3%, specificity ≥ 90.7%, and classification accuracy ≥ 90.0%. Interrater and intrarater agreements were high. CONCLUSION: This study demonstrates that airway CSAs in 3D models can be accurately estimated from depth maps. The development of artificial intelligence algorithms to compute depth maps may soon allow the quantification of airspace CSAs from clinical endoscopies.

Scaling behaviours of deep learning and linear algorithms for the prediction of stroke severity.

Deep learning has allowed for remarkable progress in many medical scenarios. Deep learning prediction models often require 105-107 examples. It is currently unknown whether deep learning can also enhance predictions of symptoms post-stroke in real-world samples of stroke patients that are often several magnitudes smaller. Such stroke outcome predictions however could be particularly instrumental in guiding acute clinical and rehabilitation care decisions. We here compared the capacities of classically used linear and novel deep learning algorithms in their prediction of stroke severity. Our analyses relied on a total of 1430 patients assembled from the MRI-Genetics Interface Exploration collaboration and a Massachusetts General Hospital-based study. The outcome of interest was National Institutes of Health Stroke Scale-based stroke severity in the acute phase after ischaemic stroke onset, which we predict by means of MRI-derived lesion location. We automatically derived lesion segmentations from diffusion-weighted clinical MRI scans, performed spatial normalization and included a principal component analysis step, retaining 95% of the variance of the original data. We then repeatedly separated a train, validation and test set to investigate the effects of sample size; we subsampled the train set to 100, 300 and 900 and trained the algorithms to predict the stroke severity score for each sample size with regularized linear regression and an eight-layered neural network. We selected hyperparameters on the validation set. We evaluated model performance based on the explained variance (R2) in the test set. While linear regression performed significantly better for a sample size of 100 patients, deep learning started to significantly outperform linear regression when trained on 900 patients. Average prediction performance improved by ∼20% when increasing the sample size 9× [maximum for 100 patients: 0.279 ± 0.005 (R2, 95% confidence interval), 900 patients: 0.337 ± 0.006]. In summary, for sample sizes of 900 patients, deep learning showed a higher prediction performance than typically employed linear methods. These findings suggest the existence of non-linear relationships between lesion location and stroke severity that can be utilized for an improved prediction performance for larger sample sizes.

Measuring palliative care integration in Malawi through service provision, access, and training indicators: the Waterloo Coalition Initiative.

BACKGROUND: Fewer than 1 in 20 people on the African continent in need of palliative care receive it. Malawi is a low-income country in sub-Saharan Africa that has yet to achieve advanced palliative care integration accompanied by unrestricted access to pain and symptom relieving palliative medicines. This paper studied the impact of Malawi's Waterloo Coalition Initiative (WCI) - a local project promoting palliative care integration through service development, staff training, and increased service access. METHODS: Interdisciplinary health professionals at 13 hospitals in southern Malawi were provided robust palliative care training over a 10-month period. We used a cross-sectional evaluation to measure palliative care integration based on 11 consensus-based indicators over a one-year period. RESULTS: 92% of hospitals made significant progress in all 11 indicators. Specifically, there was a 69% increase in the number of dedicated palliative care rooms/clinics, a total of 253 staff trained across all hospitals (a 220% increase in the region), substantive increases in the number of patients receiving or assessed for palliative care, and the number of hospitals that maintained access to morphine or other opioid analgesics while increasing the proportion of referrals to hospice or other palliative care programs. CONCLUSION: Palliative care is a component of universal health coverage and Sustainable Development Goal 3. The WCI has made tremendous strides in establishing and integrating palliative care services in Malawi with notable progress across 11 project indicators, demonstrating that increased palliative care access is possible in severely resource-constrained settings through sustained models of partnership at the local level.

Screening patients requiring secondary lumbar surgery for degenerative lumbar spine diseases: a nationwide sample cohort study.

This study aims to identify healthcare costs indicators predicting secondary surgery for degenerative lumbar spine disease (DLSD), which significantly impacts healthcare budgets. Analyzing data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database of Republic of Korea (ROK), the study included 3881 patients who had surgery for lumbar disc herniation (LDH), lumbar spinal stenosis without spondylolisthesis (LSS without SPL), lumbar spinal stenosis with spondylolisthesis (LSS with SPL), and spondylolysis (SP) from 2006 to 2008. Patients were categorized into two groups: those undergoing secondary surgery (S-group) and those not (NS-group). Surgical and interim costs were compared, with S-group having higher secondary surgery costs ($1829.59 vs $1618.40 in NS-group, P = 0.002) and higher interim costs ($30.03; 1.86% of initial surgery costs vs $16.09; 0.99% of initial surgery costs in NS-group, P < 0.0001). The same trend was observed in LDH, LSS without SPL, and LSS with SPL (P < 0.0001). Monitoring interim costs trends post-initial surgery can effectively identify patients requiring secondary surgery.

Plate-only open-door laminoplasty is associated with durable, significantly improved clinical outcomes and a very low reoperation rate for progressive spondylosis or adjacent segment disease: average 8-year follow-up.

BACKGROUND CONTEXT: Multilevel cervical myelopathy is a common cause of spinal cord dysfunction in adults. Surgical intervention via laminoplasty can provide satisfactory clinical outcomes by expansive decompression of the spinal cord. Traditional suture or bone graft techniques have been associated with insufficient fixation, leading to premature closure and subsequent neurological deterioration. In contrast, plated laminoplasty has been shown to provide stable fixation to maintain canal enlargement, but longer-term outcomes are lacking. PURPOSE: To evaluate longer-term clinical outcomes and reoperations associated with plate-only open-door laminoplasty. STUDY DESIGN: Retrospective review of prospectively collected data. PATIENT SAMPLE: Postoperative patients who underwent plate-only open door laminoplasty with minimum 5-year follow up. OUTCOME MEASURES: modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), and 12-item Short Form Health Survey (SF-12). METHODS: All patients at a single academic institution who underwent plate-only open-door cervical laminoplasty from 9/1/2006 to 9/1/2016 were identified to ensure minimum 5 year follow up. Clinical outcomes included the modified Japanese Orthopaedic Association (mJOA) score, the Neck Disability Index (NDI), and the 12-item Short Form Health Survey (SF-12). The occurrence of any repeat operations on the cervical spine was evaluated, as well as its cause. The study team attempted to contact all eligible patients to achieve at least 5 years postoperative follow-up. Pairwise t tests were performed to compare clinical outcomes at preoperative, 6 months, 1-year, and final postoperative follow-up with an α level of 0.05. RESULTS: A total of 774 met the initial inclusion criteria, of which 157 were included in the study (20.3%). Most common reasons for exclusion included inability to reach after 3 attempts (49.48%), inactive phone numbers (20.28%), and patient declining (3.49%). Included patients had an average age of 60.66±10.63 and an average follow-up time of 8.37±2.57 years (minimum 5 years). mJOA scores (preoperative 11.59±2.16) improved significantly at 6-months (14.57±2.07, p<.001), 1-year (15.19±1.95, p<.001), and final follow-up (14.59±2.63, p<.001). NDI (preoperative 33.89±18.54) improved significantly at 6 months (27.89±19.72, p=.03), 1-year (25.96±19.79, p=.01) and final follow-up (17.88±17.17, p<.001). SF-12 MCS (preoperative 44.73) improved significantly at 6 months (52.01, p=.001), 1-year (51.62, p=.008), and final follow-up (52.32, p<.001). No patient underwent reoperations for plate failure or canal closure with recurrent stenosis. Reoperations for progressive spondylosis during the follow up period were rare and occurred in only three patients for new onset radiculopathy (1.9%) and two patients for myelopathy (1.3%) at an average of 3.2 years postoperative. There were no reoperations performed for adjacent segment disease. CONCLUSIONS: At a minimum of 5 years and an average of more than 8 years postoperative, laminoplasty was associated with significant and sustained improvements in mJOA, NDI, and SF-12 MCS. Importantly, no patients underwent revision surgery for plate failure or recurrent canal closure. Reoperations for new onset radiculopathy and myelopathy were also very rare over the 8-year average follow-up period, with no reoperations for adjacent segment disease. Plate-only laminoplasty is a durable means of treating multilevel myelopathy with excellent longer-term outcomes and a very low risk of reoperation, either for premature closure or the inevitable spondylotic changes that occur over time in patients with similar baseline characteristics to the study population.

Study protocol for NeuroCARE: a randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours.

INTRODUCTION: Caregivers of patients with primary malignant brain tumours experience substantial psychological distress while caring for someone with a progressive, life-limiting neurological illness. However, there are few interventions aimed at addressing the psychosocial needs of this population. We developed and are testing a population-specific, evidence-based, telehealth intervention (NeuroCARE) to reduce anxiety symptoms and improve psychosocial functioning in this caregiver population. METHODS AND ANALYSIS: This study is a non-blinded, randomised controlled trial of a psychological intervention for caregivers of patients with primary malignant brain tumours receiving care at the Massachusetts General Hospital Cancer Center or Dana-Farber Cancer Institute. We will enrol 120 caregivers who screen positive for heightened anxiety. Participants will be randomised 1:1 to the NeuroCARE intervention or a usual care control condition. Caregivers assigned to NeuroCARE will complete six individual telehealth sessions with a trained behavioural health specialist over 12 weeks. Caregivers randomised to the control condition will receive usual care, including possible referral to social work or other appropriate resources. Participants will complete self-report questionnaires at baseline and 11 weeks and 16 weeks postrandomisation. The primary outcome is anxiety symptoms at 11 weeks among NeuroCARE participants, compared with usual care. Secondary outcomes include caregiver-reported depressive symptoms, quality of life, caregiver burden, caregiving self-efficacy, perceived coping skills and post-traumatic stress disorder symptoms. We also will explore potential mediators of the NeuroCARE effect on caregiver anxiety symptoms. ETHICS AND DISSEMINATION: The study is funded by a Career Development Award from Conquer Cancer, the American Society of Clinical Oncology Foundation (award number 2019CDA-7743456038) and approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #19-250 V.10.1). The study will be reported in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. Results will be presented at scientific meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04109209.

Palliative Care in Neuro-oncology: an Update.

PURPOSE OF REVIEW: While the benefits of palliative care for patients with cancer are well established, palliative care in neuro-oncology is still in its early stages. However, in recent years, there has been increasing attention drawn to the need for better palliative care for patients with brain tumors. RECENT FINDINGS: There is a growing body of literature demonstrating the high symptom burden and significant supportive care and information needs of these patients and their caregivers. In the area of caregiver needs, the last 3 years has seen a more rapid growth in recognizing and characterizing these needs. However, there remains a knowledge gap regarding the optimal means of addressing these needs. In this article, we outline important recent advances in the literature on palliative care for patients with brain tumors and highlight areas in need of greater attention and investigation.

Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399.

BACKGROUND: CREBBP and EP300 mutations occur at a frequency of 15% and 13%, respectively, in small cell lung cancer (SCLC), and preclinical models demonstrated susceptibility to targeting with HDAC inhibitors. METHODS: Patients with treatment-naïve extensive-stage SCLC, ECOG ≤2 were enrolled and treated with entinostat orally weekly (4 dose levels, DL) in combination with standard dose carboplatin, etoposide, and atezolizumab. Cohort allocation was determined by Bayesian optimal interval (BOIN) design targeting an MTD with a DLT rate of 20%. RESULTS: Three patients were enrolled and treated at DL1 with entinostat 2 mg. Patients were aged 69-83; 2 male, 1 female; 2 were ECOG 1, and 1 was ECOG 0. The most common adverse events (AEs) were anemia (3), neutropenia (3), thrombocytopenia (2), leukopenia (2), and hypocalcemia (2). Two experienced DLTs during cycle 1: (1) grade (Gr) 4 febrile neutropenia, and (1) Gr 5 sepsis. BOIN design required stopping accrual to DL1, and the trial was closed to further accrual. Entinostat and atezolizumab pharmacokinetics were both comparable to historical controls. CONCLUSION: Addition of entinostat to atezolizumab, carboplatin, and etoposide is unsafe and resulted in early onset and severe neutropenia, thrombocytopenia. Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).