Detection of TTR Amyloid in the Conjunctiva Using a Novel Fluorescent Ocular Tracer.

Background: Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. Methods: Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva and eye. Last, imaging of in vitro aggregated TTR amyloid labeled with AMDX-9101 was tested in a porcine ex vivo model, using a widely available clinical ophthalmic imaging device. Results: AMDX-9101 hyper-fluoresced in the presence of TTR amyloid in vitro, labeled TTR amyloid deposits in postmortem human conjunctiva and other ocular tissues and could be detected under the conjunctiva of a porcine eye using commercially available ophthalmic imaging equipment. Conclusions: AMDX-9101 enabled detection of TTR amyloid in the conjunctiva, and the fluorescent binding signal can be visualized using commercially available ophthalmic imaging equipment. Translational Relevance: AMDX-9101 detection of TTR amyloid may provide a potential new and noninvasive test for ATTR that could lead to earlier ATTR diagnosis, as well as facilitate development of new therapeutics.

Validation of Myc-Associated Protein X (MAX) regulation in growth hormone secreting and nonfunctional pituitary adenoma.

INTRODUCTION: Many patients with growth hormone-secreting pituitary adenoma (GHPA) fail to achieve biochemical remission, warranting investigation into epigenetic and molecular signatures associated with tumorigenesis and hormonal secretion. Prior work exploring the DNA methylome showed Myc-Associated Protein X (MAX), a transcription factor involved in cell cycle regulation, was differentially methylated between GHPA and nonfunctional pituitary adenoma (NFPA). We aimed to validate the differential DNA methylation and related MAX protein expression profiles between NFPA and GHPA. METHODS: DNA methylation levels were measured in 52 surgically resected tumors (37 NFPA, 15 GHPA) at ~100,000 known MAX binding sites derived using ChIP-seq analysis from ENCODE. Findings were correlated with MAX protein expression using a constructed tissue microarray (TMA). Gene ontology analysis was performed to explore downstream genetic and signaling pathways regulated by MAX. RESULTS: GHPA had more hypomethylation events across all known MAX binding sites. Of binding sites defined using ChIP-seq analysis, 1,551 sites had significantly different methylation patterns between the two cohorts; 432 occurred near promoter regions potentially regulated by MAX, including promoters of TNF and MMP9. Gene ontology analysis suggested enrichment in genes involved in oxygen response, immune system regulation, and cell proliferation. Thirteen MAX binding sites were within coding regions of genes. GHPA demonstrated significantly increased expression of MAX protein compared to NFPA. CONCLUSION: GHPA have significantly different DNA methylation and downstream protein expression levels of MAX compared to NFPA. These differences may influence mechanisms involved with cellular proliferation, tumor invasion and hormonal secretion.

Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n = 278; placebo plus chemotherapy, n = 281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio [95% CI], 0.71 [0.59 to 0.85] and 0.62 [0.52 to 0.74]), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.

Pertuzumab study in the neoadjuvant setting for HER2-positive nonmetastatic breast cancer in Australia (PeRSIA).

The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.

Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study.

BACKGROUND: Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. INTERVENTION: Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). RESULTS AND LIMITATIONS: Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65-76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22-47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0-6.5) and median OS was 14 mo (95% CI, 10.4-18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3-5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. CONCLUSIONS: Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC. PATIENT SUMMARY: Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.

Real-World Outcomes of Ribociclib and Aromatase Inhibitor Use in First Line Hormone Receptor Positive, HER2-Negative Metastatic Breast Cancer.

BACKGROUND: International guidelines recommend combining a CDK4/6 inhibitor and endocrine therapy (ET) as first line treatment for hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). Results from MONALEESA-2 demonstrate superior progression free survival (PFS) and overall survival (OS) with ribociclib (CDK4/6 inhibitor) and ET compared to ET alone. Real world outcomes have yet to be reported. MATERIALS AND METHODS: KARMA is a non-interventional registry of Australian patients receiving first-line treatment with ribociclib and aromatase inhibitor (AI), obtained via a Medicine Access Program (MAP) for HR+, HER2- MBC. Outcomes were compared with the ribociclib/letrozole cohort in MONALEESA-2. RESULTS: Data from 160 patients at 17 sites was analysed. Median follow-up is 36.5 months. Compared to MONALEESA-2, patients were numerically younger (54.3 vs. 62 years), with higher rates of bone-only metastases (31% vs. 21%). A total of 63 of 160 (39%) patients remain on treatment. A total of 56% of patients had at least 1 dose reduction, with neutropenia (68%) and abnormal liver enzymes (17%) the most common reasons. A total of 17 of 160 (11%) discontinued treatment due to toxicity, with no treatment related deaths. Median PFS was not reached (95% CI 29.9- NR), with PFS at 12 months and 18 months being 76% and 67% respectively versus 25.3 months, 73% and 63% in MONALEESA-2. CONCLUSION: The ribociclib and AI combination was well tolerated in this real-world setting. The KARMA registry cohort achieved a superior PFS (>36.5 months) to MONALEESA-2, potentially due to more favourable baseline disease characteristics. Less frequent assessment scheduling in this non trial setting may also contribute.

High rates of blood transfusion associated with Parkinson's disease.

BACKGROUND: As evidence continues to accumulate regarding the multi-organ dysfunction associated with Parkinson's disease (PD), it is still unclear as to whether PD increases the risk of hematological pathology. In this study, the authors investigate the association between PD and hematological pathology risk factors. METHODS: This retrospective cohort analysis was conducted using 8 years of the National Readmission Database. All individuals diagnosed with PD were queried at the time of primary admission. Readmissions, complications, and risk factors were analyzed at 30-, 90-, 180-, and 300-day intervals. Statistical analysis included multivariate Gaussian-fitted modeling using age, sex, comorbidities, and discharge weights as covariates. Coefficients of model variables were exponentiated and interpreted as odds ratios. RESULTS: The database query yielded 1,765,800 PD patients (mean age: 76.3 ± 10.4; 44.1% female). Rates of percutaneous blood transfusion in readmitted patients at 30, 90, 180, and 300 days were found to be 8.7%, 8.6%, 8.3%, and 8.3% respectively. Those with anti-parkinsonism medication side effects at the primary admission had increased rates of gastrointestinal (GI) hemorrhage (OR: 1.02; 95%CI: 1.01-1.03, p < 0.0001) and blood transfusion (OR: 1.06; 95%CI: 1.05-1.08, p < 0.0001) at all timepoints after readmission. PD patients who experienced GI hemorrhage of any etiology, including as a side effect of anti-parkinsonism medication, were found to have significantly higher rates of blood transfusion at all timepoints (OR: 1.14; 95%CI: 1.13-1.16, p < 0.0001). CONCLUSIONS: Blood transfusions were found to be significantly associated with anti-parkinsonism drug side effects and GI hemorrhage of any etiology.

Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: This open-label Phase III trial (NCT02264990) evaluated the PARP inhibitor, veliparib, combined with carboplatin/paclitaxel versus chemotherapy alone for first-line treatment of patients with advanced non-squamous non-small cell lung cancers (NSCLC). A 52-gene expression classifier (LP52) previously shown to identify patients more likely to respond to veliparib was evaluated as a planned correlative analysis. MATERIALS AND METHODS: Adult current or former smokers with advanced non-squamous NSCLC were randomized 1:1 to veliparib (120 mg daily for 7 days/cycle) with carboplatin and paclitaxel or to investigators' choice of platinum doublet chemotherapy (up to 6, 21-day cycles), with optional pemetrexed maintenance. Prospective analysis of the LP52 signature was conducted using a clinical Qiagen/HTG assay. The primary endpoint was overall survival (OS) in LP52+ patients. RESULTS: Overall, 595 patients received veliparib + carboplatin/paclitaxel (n = 298) or chemotherapy alone (n = 297); 13% (n = 40) in each arm were LP52+. The primary endpoint was not met; median OS was 11.2 months with veliparib + carboplatin/paclitaxel versus 9.2 months with chemotherapy alone in the LP52+ subgroup (hazard ratio [HR] 0.644, 95% confidence interval [CI]: 0.396-1.048; P = .113). In the overall population, median OS was 12.1 months in both arms (HR 0.986, 95% CI: 0.827-1.176; P = .846). No new safety signals were observed. CONCLUSION: In patients with non-squamous NSCLC, there was no significant improvement in OS with veliparib + carboplatin/paclitaxel versus chemotherapy alone, although a trend toward improved OS in the LP52+ population suggests this subgroup may benefit from veliparib. Statistical power was limited due to the small sample size.

Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) is an antifibrinolytic agent associated with reduced blood loss and mortality in a wide range of procedures, including spine surgery, traumatic brain injury, and craniosynostosis. Despite this wide use, the safety and efficacy of TXA in spine surgery has been considered controversial due to a relative scarcity of literature and lack of statistical power in reported studies. However, if TXA can be shown to reduce blood loss in laminectomy with fusion and posterior instrumentation, more surgeons may include it in their armamentarium. The authors aimed to conduct an up-to-date systematic review and meta-analysis of the efficacy of TXA in reducing blood loss in laminectomy and fusion with posterior instrumentation. METHODS: A systematic review and meta-analysis, abiding by PRISMA guidelines, was performed by searching the databases of PubMed, Web of Science, and Cochrane. These platforms were queried for all studies reporting the use of TXA in laminectomy and fusion with posterior instrumentation. Variables retrieved included patient demographics, surgical indications, involved spinal levels, type of laminectomy performed, TXA administration dose, TXA route of administration, operative duration, blood loss, blood transfusion rate, postoperative hemoglobin level, and perioperative complications. Heterogeneity across studies was evaluated using a chi-square test, Cochran's Q test, and I2 test performed with R statistical programming software. RESULTS: A total of 7 articles were included in the qualitative study, while 6 articles featuring 411 patients underwent statistical analysis. The most common route of administration for TXA was intravenous with 15 mg/kg administered preoperatively. After the beginning of surgery, TXA administration patterns were varied among studies. Blood transfusions were increased in non-TXA cohorts compared to TXA cohorts. Patients administered TXA demonstrated a significant reduction in blood loss (mean difference -218.44 mL; 95% CI -379.34 to -57.53; p = 0.018). TXA administration was not associated with statistically significant reductions in operative durations. There were no adverse events reported in either the TXA or non-TXA patient cohorts. CONCLUSIONS: TXA can significantly reduce perioperative blood loss in cervical, thoracic, and lumbar laminectomy and fusion procedures, while demonstrating a minimal complication profile.

Citation analysis of the most influential ependymoma research articles illustrates improved knowledge of the molecular biology of ependymoma.

The history of academic research on ependymoma is expansive. This review summarizes its history with a bibliometric analysis of the 100 most cited articles on ependymoma. In March 2020, we queried the Web of Science database to identify the most cited articles on ependymoma using the terms "ependymoma" or "ependymal tumors," yielding 3145 publications. Results were arranged by the number of times each article was cited in descending order. The top 100 articles spanned across nearly a century; the oldest article was published in 1924, while the most recent was in 2017. These articles were published in 35 unique journals, including a mix of basic science and clinical journals. The three institutions with the most papers in the top 100 were St. Jude Children's Research Hospital (16%), the University of Texas MD Anderson Cancer Center (6%), and the German Cancer Research Center (5%). We analyzed the publications that may be considered the most influential in the understanding and treatment management of ependymoma. Studies focused on the molecular classification of ependymomas were well-represented among the most cited articles, reflecting the field's current area of focus and its future directions. Additionally, this article also offers a reference for further studies in the ependymoma field.

Outcomes With Pembrolizumab Plus Platinum-Based Chemotherapy for Patients With NSCLC and Stable Brain Metastases: Pooled Analysis of KEYNOTE-021, -189, and -407.

INTRODUCTION: This exploratory analysis retrospectively evaluated outcomes in patients with advanced NSCLC to determine whether baseline brain metastases influenced the efficacy of first-line pembrolizumab plus chemotherapy versus chemotherapy alone. METHODS: We pooled data for patients with advanced NSCLC in KEYNOTE-021 cohort G (nonsquamous), KEYNOTE-189 (nonsquamous), and KEYNOTE-407 (squamous). Patients were assigned to platinum-doublet chemotherapy with or without the addition of 35 cycles of pembrolizumab 200 mg every 3 weeks. All studies permitted enrollment of patients with previously treated or untreated (KEYNOTE-189 and KEYNOTE-407 only) stable brain metastases. Patients with previously treated brain metastases were clinically stable for 2 or more weeks (≥4 wk in KEYNOTE-021 cohort G), had no evidence of new or enlarging brain metastases, and had no steroid use at least 3 days before dosing. Patients with known untreated asymptomatic brain metastases required regular imaging of the brain. RESULTS: A total of 1298 patients were included, 171 with and 1127 without baseline brain metastases. Median (range) durations of follow-up at data cutoff were 10.9 (0.1‒35.1) and 11.0 (0.1‒34.9) months, respectively. Hazard ratios (pembrolizumab + chemotherapy/chemotherapy) were similar for patients with and without brain metastases for overall survival (0.48 [95% confidence interval (CI): 0.32‒0.70] and 0.63 [95% CI: 0.53‒0.75], respectively) and progression-free survival (0.44 [95% CI: 0.31‒0.62] and 0.55 [95% CI: 0.48‒0.63], respectively). In patients with brain metastases, median overall survival was 18.8 months with pembrolizumab plus chemotherapy and 7.6 months with chemotherapy, and median progression-free survival was 6.9 months and 4.1 months, respectively. Objective response rates were higher and duration of response longer with pembrolizumab plus chemotherapy versus chemotherapy regardless of brain metastasis status. Incidences of treatment-related adverse events with pembrolizumab plus chemotherapy versus chemotherapy were 88.2% versus 82.8% among patients with brain metastases and 94.5% versus 90.6% in those without. CONCLUSIONS: With or without brain metastasis, pembrolizumab plus platinum-based histology-specific chemotherapy improved clinical outcomes versus chemotherapy alone across all programmed death ligand 1 subgroups, including patients with programmed death ligand 1 tumor proportion score less than 1% and had a manageable safety profile in patients with advanced NSCLC. This regimen is a standard-of-care treatment option for treatment-naive patients with advanced NSCLC, including patients with stable brain metastases.

Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50.

PURPOSE: We report the first 5-year follow-up of any first-line phase III immunotherapy trial for non-small-cell lung cancer (NSCLC). KEYNOTE-024 (ClinicalTrials.gov identifier: NCT02142738) is an open-label, randomized controlled trial of pembrolizumab compared with platinum-based chemotherapy in patients with previously untreated NSCLC with a programmed death ligand-1 (PD-L1) tumor proportion score of at least 50% and no sensitizing EGFR or ALK alterations. Previous analyses showed pembrolizumab significantly improved progression-free survival and overall survival (OS). METHODS: Eligible patients were randomly assigned (1:1) to pembrolizumab (200 mg once every 3 weeks for up to 35 cycles) or platinum-based chemotherapy. Patients in the chemotherapy group with progressive disease could cross over to pembrolizumab. The primary end point was progression-free survival; OS was a secondary end point. RESULTS: Three hundred five patients were randomly assigned: 154 to pembrolizumab and 151 to chemotherapy. Median (range) time from randomization to data cutoff (June 1, 2020) was 59.9 (55.1-68.4) months. Among patients initially assigned to chemotherapy, 99 received subsequent anti-PD-1 or PD-L1 therapy, representing a 66.0% effective crossover rate. Median OS was 26.3 months (95% CI, 18.3 to 40.4) for pembrolizumab and 13.4 months (9.4-18.3) for chemotherapy (hazard ratio, 0.62; 95% CI, 0.48 to 0.81). Kaplan-Meier estimates of the 5-year OS rate were 31.9% for the pembrolizumab group and 16.3% for the chemotherapy group. Thirty-nine patients received 35 cycles (ie, approximately 2 years) of pembrolizumab, 82.1% of whom were still alive at data cutoff (approximately 5 years). Toxicity did not increase with longer treatment exposure. CONCLUSION: Pembrolizumab provides a durable, clinically meaningful long-term OS benefit versus chemotherapy as first-line therapy for metastatic NSCLC with PD-L1 tumor proportion score of at least 50%.

Getting Down to the Bare Bones: Does laminoplasty or laminectomy With Fusion Provide Better Outcomes for Patients With Multilevel Cervical Spondylotic Myelopathy?

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a degenerative disorder leading to progressive decline in spinal cord function. Cervical laminoplasty (CLP) and cervical laminectomy with fusion (CLF) are standard treatments for multilevel CSM. However, it is still unclear whether one procedure over the other provides better outcomes. Here, we performed a comprehensive review of published articles that compare the clinical outcomes and costs between CLP and CLF for CSM. METHODS: A literature search was performed using PubMed, Web of Science, and Cochrane databases. Strict exclusion criteria were applied, and included articles were then assessed for publication year, study design, and significant differences in outcome variables. RESULTS: From 519 studies identified with search terms, 38 studies were included for the qualitative analysis. Statistically significant differences in the clinical outcomes and costs were found in 18 studies. Eleven studies were prospective or retrospective, and 8 studies were meta-analyses. For the outcome variables of interest, results were reported by classifying into prospective studies, retrospective studies, and meta-analyses. CONCLUSION: CLP and CLF are 2 of the most commonly performed surgical procedures for the treatment of CSM. Although CLP and CLF each provide satisfactory clinical outcomes for patients with CMS, CLP may result in better cervical range of motion and less cost, length of stay, operation time, blood loss, paraspinal muscular atrophy, and rate of nerve palsies as compared to CLF. The major limitation of CLP versus CLF comparison studies includes the heterogeneity in techniques and preoperative criteria. Thus, further validation and investigations in larger cohorts will be required.

Ethical considerations and patient safety concerns for cancelling non-urgent surgeries during the COVID-19 pandemic: a review.

At the time of writing of this article, there have been over 110 million cases and 2.4 million deaths worldwide since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, postponing millions of non-urgent surgeries. Existing literature explores the complexities of rationing medical care. However, implications of non-urgent surgery postponement during the COVID-19 pandemic have not yet been analyzed within the context of the four pillars of medical ethics. The objective of this review is to discuss the ethics of elective surgery cancellation during the COVID-19 pandemic in relation to beneficence, non-maleficence, justice, and autonomy. This review hypothesizes that a more equitable decision-making algorithm can be formulated by analyzing the ethical dilemmas of elective surgical care during the pandemic through the lens of these four pillars. This paper's analysis shows that non-urgent surgeries treat conditions that can become urgent if left untreated. Postponement of these surgeries can cause cumulative harm downstream. An improved algorithm can address these issues of beneficence by weighing local pandemic stressors within predictive algorithms to appropriately increase surgeries. Additionally, the potential harms of performing non-urgent surgeries extend beyond the patient. Non-maleficence is maintained through using enhanced screening protocols and modifying surgical techniques to reduce risks to patients and clinicians. This model proposes a system to transfer patients from areas of high to low burden, addressing the challenge of justice by considering facility burden rather than value judgments concerning the nature of a particular surgery, such as cosmetic surgeries. Autonomy can be respected by giving patients the option to cancel or postpone non-urgent surgeries. However, in the context of limited resources in a global pandemic, autonomy is not absolute. Non-urgent surgeries can ethically be postponed in opposition to the patient's preference. The proposed algorithm attempts to uphold the four principles of medical ethics in rationing non-urgent surgical care by building upon existing decision models, using additional measures of resource burden and surgical safety to increase health care access and decrease long-term harm as much as possible. The next global health crisis will undoubtedly present its own unique challenges. This model may serve as a comprehensive starting point in determining future guidelines for non-urgent surgical care.

Predictors of Patient Satisfaction in Spine Surgery: A Systematic Review.

BACKGROUND: Recently, there has been increased interest in patient satisfaction measures such as Press Ganey and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys. In this systematic review, the spine surgery literature is analyzed to evaluate factors predictive of patient satisfaction as measured by these surveys. METHODS: A thorough literature search was performed in PubMed/MEDLINE, Google Scholar, and Cochrane databases. All English-language articles from database inception to July 2020 were screened for study inclusion according to PRISMA guidelines. RESULTS: Twenty-four of the 1899 published studies were included for qualitative analysis. There has been a statistically significant increase in the number of publications across years (P = 0.04). Overall, the studies evaluated the relationship between patient satisfaction and patient demographics (71%), preoperative and intraoperative clinical factors (21%), and postoperative factors (33%). Top positive predictors of patient satisfaction were patient and nursing/medical staff relationship (n = 4; 17%), physician-patient relationship (n = 4; 17%), managerial oversight of received care (n = 3; 13%), same sex/ethnicity between patient and physician (n = 2; 8%), and older age (n = 2; 8%). Top negative predictors of patient satisfaction were high Charlson Comorbidity Index/high disability/worse overall health functioning (n = 7; 29%), increased length of hospital stay (n = 4; 17%), high rating for pain/complications/readmissions (n = 4; 17%), and psychosocial factors (n = 3; 13%). CONCLUSIONS: There is heterogeneity in terms of different factors, both clinical and nonclinically related, that affect patient satisfaction ratings. More research is warranted to investigate the role of hospital consumer surveys in the spine surgical patient population.

Indication-based analysis of patient outcomes following deep brain stimulation surgery.

BACKGROUND: While considered a safe operation, deep brain stimulation (DBS) has been associated with various morbidities. We assessed differences in postsurgical complication rates in patients undergoing the most common types of neurostimulation surgery. METHODS: The National Readmission Database (NRD) was queried to identify patients undergoing neurostimulation placement with the diagnosis of Parkinson disease (PD), epilepsy, dystonia, or essential tremor (ET). Demographics and complications, including infection, pneumonia, and neurostimulator revision, were queried for each cohort and compiled. Readmissions were assessed in 30-, 90-, and 180-day intervals. We implemented nearest-neighbor propensity score matching to control for demographic and sample size differences between groups. RESULTS: We identified 3230 patients with Parkinson disease, 1289 with essential tremor, 965 with epilepsy, and 221 with dystonia. Following propensity score matching, 221 patients remained in each cohort. Readmission rates 30-days after hospital discharge for PD patients (15.5 %) were significantly greater than those for ET (7.8 %) and seizure patients (4.4 %). Pneumonia was reported for PD (1.6 %), seizure (3.3 %) and dystonia (1.7 %) patients but not individuals ET. No PD patients were readmitted at 30-days due to dysphagia while individuals treated for ET (6.5 %), seizure (1.6 %) and dystonia (5.2 %) were. DBS-revision surgery was performed for 11.48 % of PD, 6.52 % of ET, 1.64 % of seizure and 6.90 % of dystonia patients within 30-days of hospital discharge. CONCLUSION: 30-day readmission rates vary significantly between indications, with patients receiving DBS for PD having the highest rates. Further longitudinal studies are required to describe drivers of variation in postoperative outcomes following DBS surgery for different indications.

The 100 Most Influential Publications on Medulloblastoma: Areas of Past, Current, and Future Focus.

BACKGROUND: This article is the first to identify the most influential articles on medulloblastoma using the citation analysis methodology. OBJECTIVE: To perform a bibliometric analysis of the 100 most-cited articles on medulloblastoma. METHODS: Using the Web of Science database, search criteria included the title-specific keyword "medulloblastoma" OR "cerebellar primitive neuroectodermal tumor (PNET)" OR "cerebellar PNET." Publications from 1900 to 2020 labeled "article," "review," "data set," or "clinical trial" were chosen and ranked based on total number of citations in descending order. Each article was evaluated based on the following variables: total citations, average citations per year, first author, institution of first author, title, publication year, country of origin, SCImago Journal Rank, and Scopus SNIP (Source Normalized Impact per Paper). RESULTS: Our search yielded 4928 articles on medulloblastoma. The 100 most-cited articles ranged from 192 to 2017 across 42 unique journals; Journal of Clinical Oncology accounted for the most publications (16%). Paul A. Northcott was first author of the most articles on the list (n = 7.7%), and the most widely cited article was "Altered neural cell fates and medulloblastoma in mouse patched mutants" by Goodrich et al., published in Science (1997). CONCLUSIONS: Because medulloblastoma represents the most common form of pediatric cancerous brain tumor, it is important to identify works that have significantly contributed to the body of knowledge regarding this disease. The 100 most-cited medulloblastoma articles comprise a significant collection of data regarding the histopathologic and molecular classification of medulloblastoma as well as clinical outcomes of therapeutics used to treat this disease.

Spinal pathologies and management strategies associated with cervical angina (pseudoangina): a systematic review.

OBJECTIVE: Cervical angina, or pseudoangina pectoris, is a noncardiac syndrome of chest pain that often mimics angina pectoris but is a disease of the spine. Diagnosis of cervical angina can be difficult and is often overlooked, although once identified, it can be successfully managed through conservative therapies and/or a variety of surgical interventions. Ultimately, cervical angina is an important component of the list of differential diagnoses in noncardiac chest pain. In the present study, the authors report the first comprehensive systematic review of the range of cervical and thoracic pathologies associated with cervical angina, as well as the different treatment methods used to manage this condition. METHODS: A systematic review was performed according to PRISMA guidelines and using PubMed, Web of Science, and Cochrane databases from database inception to April 29, 2020, to identify studies describing spinal pathologies related to cervical angina. The following Boolean search was performed: ("cervical" OR "thoracic") AND ("angina" OR "chest pain") AND ("herniation" OR "OPLL"). Variables extracted included patient demographics, cervical angina pain location, pathology and duration of symptoms, treatment and/or management method, and posttreatment pain relief. RESULTS: Upon careful screening, 22 articles published between 1976 and 2020 met the study's inclusion/exclusion criteria, including 5 case series, 12 case reports, and 5 retrospective cohort studies. These studies featured a total of 1100 patients, of which 95 met inclusion criteria (mean patient age 51.7 years, age range 24-86 years; 53.6% male). Collectively, symptom durations ranged from 1.5 days to 90 months. Cervical herniation (72.6%) accounted for the majority of cervical angina cases, and surgical interventions (84.4%) predominated over physical therapy (13.0%) and medical management strategies (9.1%). Every patient assessed at follow-up reported relief from symptoms related to cervical angina. CONCLUSIONS: Cervical angina is a noncardiac syndrome of chest pain associated with a broad range of cervical and thoracic spinal pathologies, the most common of which is cervical disc herniation. Although difficult to diagnose, it can be successfully treated when identified through first-line conservative management or surgical interventions in refractory cases.

The role of frailty in geriatric cranial neurosurgery for primary central nervous system neoplasms.

OBJECTIVE: Frailty is a clinical state of increased vulnerability due to age-associated decline and has been well established as a perioperative risk factor. Geriatric patients have a higher risk of frailty, higher incidence of brain cancer, and increased postoperative complication rates compared to nongeriatric patients. Yet, literature describing the effects of frailty on short- and long-term complications in geriatric patients is limited. In this study, the authors evaluate the effects of frailty in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. METHODS: The authors conducted a retrospective cohort study of geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm between 2010 and 2017 by using the Nationwide Readmission Database. Demographics and frailty were queried at primary admission, and readmissions were analyzed at 30-, 90-, and 180-day intervals. Complications of interest included infection, anemia, infarction, kidney injury, CSF leak, urinary tract infection, and mortality. Nearest-neighbor propensity score matching for demographics was implemented to identify nonfrail control patients with similar diagnoses and procedures. The analysis used Welch two-sample t-tests for continuous variables and chi-square test with odds ratios. RESULTS: A total of 6713 frail patients and 6629 nonfrail patients were identified at primary admission. At primary admission, frail geriatric patients undergoing cranial neurosurgery had increased odds of developing acute posthemorrhagic anemia (OR 1.56, 95% CI 1.23-1.98; p = 0.00020); acute infection (OR 3.16, 95% CI 1.70-6.36; p = 0.00022); acute kidney injury (OR 1.32, 95% CI 1.07-1.62; p = 0.0088); urinary tract infection prior to discharge (OR 1.97, 95% CI 1.71-2.29; p < 0.0001); acute postoperative cerebral infarction (OR 1.57, 95% CI 1.17-2.11; p = 0.0026); and mortality (OR 1.64, 95% CI 1.22-2.24; p = 0.0012) compared to nonfrail geriatric patients receiving the same procedure. In addition, frail patients had a significantly increased inpatient length of stay (p < 0.0001) and all-payer hospital cost (p < 0.0001) compared to nonfrail patients at the time of primary admission. However, no significant difference was found between frail and nonfrail patients with regard to rates of infection, thromboembolism, CSF leak, dural tear, cerebral infarction, acute kidney injury, and mortality at all readmission time points. CONCLUSIONS: Frailty may significantly increase the risks of short-term acute complications in geriatric patients receiving cranial neurosurgery for a primary CNS neoplasm. Long-term analysis revealed no significant difference in complications between frail and nonfrail patients. Further research is warranted to understand the effects and timeline of frailty in geriatric patients.