Meningioma recurrence: Time for an online prediction tool?

Background: Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient's lifespan. In addition, with the emergence of several clinical, radiological, and molecular variables, it is becoming evident that existing grading criteria, including Simpson's and World Health Organization classification, may not be sufficient or accurate. As web-based tools for widespread accessibility and usage become commonplace, such as those for gene identification or other cancers, it is timely for meningioma care to take advantage of evolving new markers to help advance patient care. Methods: A scoping review of the meningioma literature was undertaken using the MEDLINE and Embase databases. We reviewed original studies and review articles from September 2022 to December 2023 that provided the most updated information on the demographic, clinical, radiographic, histopathological, molecular genetics, and management of meningiomas in the adult population. Results: Our scoping review reveals a large body of meningioma literature that has evaluated the determinants for recurrence and aggressive tumor biology, including older age, female sex, genetic abnormalities such as telomerase reverse transcriptase promoter mutation, CDKN2A deletion, subtotal resection, and higher grade. Despite a large body of evidence on meningiomas, however, we noted a lack of tools to aid the clinician in decision-making. We identified the need for an online, self-updating, and machine-learning-based dynamic model that can incorporate demographic, clinical, radiographic, histopathological, and genetic variables to predict the recurrence risk of meningiomas. Conclusion: Although a challenging endeavor, a recurrence prediction tool for meningioma would provide critical information for the meningioma patient and the clinician making decisions on long-term surveillance and management of meningiomas.

Epicardial placement of human placental membrane protects from heart injury in a swine model of myocardial infarction.

Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC-treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.

Pre-registered controlled comparison of auditory function reveals no difference between hospitalised adults with and without COVID-19.

OBJECTIVE: Several viruses are known to have a negative impact on hearing health. The global prevalence of COVID-19 means that it is crucial to understand whether and how SARS-CoV2 affects hearing. Evidence to date is mixed, with studies frequently exhibiting limitations in the methodological approaches used or the populations sampled, leading to a substantial risk of bias. This study addressed many of these limitations. DESIGN: A comprehensive battery of measures was administered, including lab-based behavioural and physiological measures, as well as self-report instruments. Performance was thoroughly assessed across the auditory system, including measures of cochlear function, neural function and auditory perception. Hypotheses and analyses were pre-registered. STUDY SAMPLES: Participants who were hospitalised as a result of COVID-19 (n = 57) were compared with a well-matched control group (n = 40) who had also been hospitalised but had never had COVID-19. RESULTS: We find no evidence to support the hypothesis that COVID-19 is associated with deficits in auditory function on any auditory test measure. Of all the confirmatory analyses, only the self-report measure of hearing decline indicated any difference between groups. CONCLUSION: Results do not support the hypothesis that COVID-19 infection has a significant long-term impact on the auditory system.

Propensity Score Matching: A Powerful Tool for Analyzing Observational Nonrandomized Data.

In using observational, nonrandomized data, there is often interest in studying the effect of a particular treatment on a specific outcome. However, the imbalance of potential confounding variables between the treatment groups can distort the relationship between treatment and outcome. Propensity score matching is one, increasingly utilized, method to help account for such imbalances, allowing for a more accurate estimation of the influence of treatment on outcome. In this paper, we provide the clinician with an overview of propensity score matching techniques and provide a practical example of how this has been used in clinical research relevant to spine surgery.

Blood-Brain Barrier Disruption in Neuro-Oncology: Strategies, Failures, and Challenges to Overcome.

The blood-brain barrier (BBB) presents a formidable challenge in the development of effective therapeutics in neuro-oncology. This has fueled several decades of efforts to develop strategies for disrupting the BBB, but progress has not been satisfactory. As such, numerous drug- and device-based methods are currently being investigated in humans. Through a focused assessment of completed, active, and pending clinical trials, our first aim in this review is to outline the scientific foundation, successes, and limitations of the BBBD strategies developed to date. Among 35 registered trials relevant to BBBD in neuro-oncology in the ClinicalTrials.gov database, mannitol was the most common drug-based method, followed by RMP-7 and regadenoson. MR-guided focused ultrasound was the most common device-based method, followed by MR-guided laser ablation, ultrasound, and transcranial magnetic stimulation. While most early-phase studies focusing on safety and tolerability have met stated objectives, advanced-phase studies focusing on survival differences and objective tumor response have been limited by heterogeneous populations and tumors, along with a lack of control arms. Based on shared challenges among all methods, our second objective is to discuss strategies for confirmation of BBBD, choice of systemic agent and drug design, alignment of BBBD method with real-world clinical workflow, and consideration of inadvertent toxicity associated with disrupting an evolutionarily-refined barrier. Finally, we conclude with a strategic proposal to approach future studies assessing BBBD.

The Role of Stereotactic Radiosurgery in the Management of Brain Metastases From a Health-Economic Perspective: A Systematic Review.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective option in the management of brain metastases, offering improved overall survival to whole-brain radiation therapy (WBRT). However, given the need for active surveillance and the possibility of repeated interventions for local/distant brain recurrences, the balance between clinical benefit and economic impact must be evaluated. OBJECTIVE: To conduct a systematic review of health-economic analyses of SRS for brain metastases, compared with other existing intervention options, to determine the cost-effectiveness of this treatment across different clinical scenarios. METHODS: The MEDLINE, EMBASE, Cochrane, CRD, and EconLit databases were searched for health-economic analyses, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using terms relevant to brain metastases and radiation-based therapies. Simple cost analysis studies were excluded. Quality analysis was based on BMJ Consolidated Health Economics Reporting Standards (CHEERS) checklist. RESULTS: Eleven eligible studies were identified. For lesions with limited mass effect, SRS was more cost-effective than surgical resection (6 studies). In patients with Karnofsky performance scale (KPS) >70 and good predicted survival, SRS was cost-effective compared to WBRT (7 studies); WBRT became cost-effective with poor performance status or low anticipated life span. Following SRS, routine magnetic resonance imaging surveillance saved $1326/patient compared to symptomatic imaging due to reduced surgical salvage and hospital stay (1 study). CONCLUSION: Based on our findings, SRS is cost-effective in the management of brain metastases, particularly in high-functioning patients with longer expected survival. However, before an optimal care pathway can be proposed, emerging factors such as tumor molecular subtype, diagnosis-specific graded prognostic assessment, neuroprognostic score, tailored surveillance imaging, and patient utilities need to be studied in greater detail.

Comparing Effects of Treatment: Controlling for Confounding.

BACKGROUND: Determining true causal links between an intervention and an outcome forms an imperative task in research studies in neurosurgery. Although the study results sometimes demonstrate clear statistical associations, it is important to ensure that this represents a true causal link. A confounding variable, or confounder, affects the association between a potential predictor and an outcome. OBJECTIVE: To discuss what confounding is and the means by which it can be eliminated or controlled. METHODS: We identified neurosurgical research studies demonstrating the principles of eliminating confounding by means of study design and data analysis. RESULTS: In this report, we outline the role of confounding in neurosurgical studies after giving an overview of its identification. We report on the definition of confounding and effect modification, and the differences in the 2. We explain study design techniques to eliminate confounding, including simple, block, stratified, and minimization randomization, along with restriction of sample and matching. Data analysis techniques of eliminating confounding include regression analysis, propensity scoring, and subgroup analysis. CONCLUSION: Understanding confounding is important for conducting a good research study. Study design techniques provide the best way to control for confounders, but when not possible to alter study design, data analysis techniques can also provide an effective control.

The Effect of Older Age on the Perioperative Outcomes of Spinal Fusion Surgery in Patients With Lumbar Degenerative Disc Disease With Spondylolisthesis: A Propensity Score-Matched Analysis.

BACKGROUND: Degenerative spondylolisthesis (DS) is often treated with lumbar spinal fusion (LSF). However, there is concern that the morbidity of LSF may be prohibitively high in older adults. OBJECTIVE: To evaluate the impact of advanced age on the safety of LSF for DS. METHODS: Patients who underwent LSF for DS were retrospectively identified from National Surgical Quality Improvement Program datasets for 2011 to 2015 using Current Procedural Terminology codes. Data on demographic characteristics, comorbidities, surgical factors, and 30-d morbidity and mortality were collected. Propensity score matching (nearest neighbor) was performed with age (<70 vs ≥70 yr) as the dependent variable and sex, type of fusion procedure, number of levels fused, diabetes, smoking, hypertension, and chronic steroid use as covariates. Outcomes were compared between age <70 and ≥70 groups. RESULTS: The study cohort consisted of 2238 patients (n = 1119, age <70; n = 1119, age ≥70). The 2 age groups were balanced for key covariates including sex, race, diabetes, hypertension, CHF, smoking, chronic steroid use, type of fusion, and number of levels. Rates of all complications were similar between younger and older age groups, except urinary tract infection, which was more frequent among the ≥70 age group (OR 2.32, P = .009). Further, patients in the older age group were more likely to be discharged to a rehabilitation (OR 2.94, P < .001) or skilled care (OR 3.66, P < .001) facility, rather than directly home (OR 0.25, P < .001). CONCLUSION: LSF may be performed safely in older adults with DS. Our results suggest older age alone should not exclude a patient from undergoing lumbar fusion for DS.

MGMT Testing in Glioblastomas: Pitfalls and Opportunities.

Gliomas, that do not respond to alkylating agent chemotherapy, can be made more sensitive to chemotherapy through promotor mediated epigenetic silencing of the MGMT gene. MGMT is one of the important markers in glioblastomas as it not only predicts response to therapy but may also be used as an independent prognostic marker. As such, MGMT is gaining increasing traction in diagnosis, prognostication, and therapeutic decision-making for these highly malignant gliomas. Although, MGMT promotor methylation status is becoming more commonly used in neuro-oncology; this test remains imperfect. Because of its increasing use in clinical practice and research, it is integral that we are aware of its pitfalls and complications. Currently, there are many ways to detect a patient's MGMT promotor methylation status, including: quantitative PCR, methylation-specific PCR, pyrosequencing, real time PCR with high resolution melt, and the infinitum methylation EPIC beadChip. The technical aspects, shortcomings, and optimal approach to interpreting the results of each method will be discussed. Furthermore, given that none of these methods have been prospectively validated, the challenge of equivocal cases will be discussed, and technical and logistic strategies for overcoming these challenges will be proposed. Finally, the difficulty in validating these methods, establishing standardized practice, and considerations of the cost of these competing methods will be explored.

Bone and joint mycobacterial infection: a retrospective review of cases presenting to a UK district hospital.

PURPOSE: Peterborough has one of the highest rates of tuberculosis (TB) in the east of England. We reviewed the epidemiology, management and outcome of all cases of bone and joint TB (BJTB) diagnosed since 2000. METHODOLOGY: Retrospective review of all adult cases of BJTB between 1 January 2000 and 31 December 2015. Patients' notes were reviewed with regard to their presentation, investigation, management and outcomes. RESULTS: In total, 21 patients diagnosed with BJTB were reviewed. Thoracic and lumbar spine were the most common sites affected (62 %). The most common clinical manifestations included localized pain (76 %), fever (53 %) and weight loss (48 %). Fourteen (67 %) patients had a bone biopsy or aspirate sent for microbiological investigation; none were smear-positive, but 11 were culture-positive. Eleven patients (77 %) were fully susceptible to anti-tuberculous drugs, one was isoniazid-resistant and one was pyrazinamide-resistant. Anti-tuberculous therapy was given for 6-16 months. Nineteen (90 %) patients completed therapy. CONCLUSIONS: BJTB requires a high index of clinical suspicion. BJTB should be considered in any patient with unexplained pain, fever and weight loss. The diagnosis is proven by aspiration and biopsy and should be undertaken as soon as possible for culture purposes, as microscopy alone can be negative.

Medical and socioeconomic predictors of quality of life in myelomeningocele patients with shunted hydrocephalus.

INTRODUCTION: Children with myelomeningocele (MMC) often develop hydrocephalus, and the combination of these conditions can lead to psychosocial, cognitive, and physical health issues that decrease their health-related quality of life (HRQOL). The goal of the present study was to understand the QOL in patients with MMC and shunted hydrocephalus. METHODS: Data from the Toronto Hydrocephalus QOL Database was acquired between 2004 and 2009 using parent-completed questionnaires and, when appropriate, child-completed questionnaires: Hydrocephalus Outcome Questionnaire (HOQ) and the Health Utilities Index. We identified several medical and socioeconomic factors potentially relevant to the outcome measure (e.g., level of myelomeningocele, length of stay in hospital, and shunt-related hospital admissions; family functioning, income, parental education, employment status, etc.). Linear regression models were used to examine associations between potential predictor variables and HRQOL, with P < 0.05 in the multivariate model suggesting significance. RESULTS: The analysis consisted of 131 patients (mean age = 12.6, SD = 3.7). The mean HUI score was 0.51, and the mean HOQ overall health score was 0.67. There was a significant association between lower age and higher HOQ social-emotional health (P = 0.03) and HUI scores (P = 0.03), lower anatomical level of myelomeningocele and higher HUI scores (P = 0.01), better family functioning and higher HOQ overall health scores (P = 0.004), and higher family income and higher HOQ overall health, physical health, and HUI scores (P = 0.001, P = 0.003, and P = 0.02, respectively). CONCLUSION: Myelomeningocele patients with shunted hydrocephalus can have a poor health-related quality of life. Our results indicate a strong association of income and family functioning on quality of life, along with younger age and lower level of myelomeningocele.

Tuberculosis screening in a dialysis unit: detecting latent tuberculosis infection is only half the problem.

Patients with chronic kidney disease are at increased risk of tuberculosis. We describe the events that occurred when we encountered a patient receiving haemodialysis with pulmonary tuberculosis. Nine (of 41) patients dialysing at the same time as the index case had a positive interferon-gamma release assay (IGRA) and were offered therapy for latent tuberculosis infection (LTBI). Patients with an initial negative IGRA were rescreened at six months, identifying a further three IGRA-positive patients. All patients were then rescreened at 12 months. No new IGRA-positive cases were identified and no staff or patients developed active disease. Only five of the 12 IGRA-positive patients completed LTBI therapy.

Treating tuberculosis in the elderly population: a lesson in multi-disciplinary care.

INTRODUCTION: It is estimated that the risk of reactivation of previously untreated healed or latent tuberculosis is around 0.04 cases per 100 person-years. The incidence of active tuberculosis in Peterborough is 28.0 per 100,000 population compared with 8.3 in the East of England region. The majority of patients are of Indian or Pakistani origin and aged between 15 and 65. CASE PRESENTATION: Here, we present the case of an 88-year-old gentleman who successfully completed anti-tuberculous therapy for smear-negative tuberculosis and discuss some of the issues encountered in his management, with particular emphasis on drug surveillance, tolerance of anti-tuberculous therapy and drug interactions. CONCLUSION: Elderly persons presenting with tuberculosis are more likely to present atypically and may need a staged initiation of therapy with continued pharmacist advice, due to high risk of interactions.

Abdominal tuberculosis: a retrospective review of cases presenting to a UK district hospital.

INTRODUCTION: Peterborough has one of the highest rates of tuberculosis in the East of England; ∼40% of TB treated locally is extra-pulmonary. AIM AND METHODS: All adults diagnosed with abdominal tuberculosis (ATB) between January 2008 and September 2011 in Peterborough Hospitals were retrospectively evaluated with regard to their clinical history, investigation, management and outcomes. RESULTS: In total, 17 patients diagnosed with ATB were reviewed. All the patients were from (or descended from) high-risk ethnic groups. Four had co-existing pulmonary TB. Intestinal and peritoneal TB were the most common findings. The most common clinical manifestations included abdominal pain (71%), weight loss (59%), diarrhoea (47%) and pyrexia (41%). Fifteen patients had samples sent for microbiological investigation; 1 (6%) was smear positive and 9 (53%) were culture positive. Two (12%) were isoniazid resistant. No rifampicin resistance was detected. Anti-tuberculous therapy was given for 6-12 months. In total, 16 (94%) patients completed the treatment; 1 patient died prior to regime completion (crude mortality: 6%). There was one reported case of pyrazinamide intolerance and two episodes of isoniazid intolerance. DISCUSSION: ATB is a diagnostic challenge, especially in absence of lung involvement. It mimics other diseases and clinical presentation is usually non-specific, which may lead to diagnostic delay and development of complications. Extreme vigilance should be used when dealing with unexplained abdominal symptoms to ensure timely diagnosis of ATB. Early diagnosis with early anti-tuberculous therapy and surgical treatment are essential to ensure as positive an outcome as possible.

Cardiac amyloidosis and the use of diuretic and ACE inhibitor therapy in severe heart failure.

The underlying cause of heart failure should be established, where possible. In particular the failure to respond to diuretic and vasodilator therapy requires careful evaluation.