The Anterior Interhemispheric Transcallosal Approach to the Ventricles: How We Do It.

Intraventricular tumors of the lateral and third ventricles are relatively rare, accounting for 1-2% of all primary brain tumors in most large series [1-4]. They can be uniquely challenging to approach due to their deep location, propensity to become large before they are discovered, and association with hydrocephalus [5, 6]. The surgeon's goal is to develop a route to these deep lesions that will cause the least morbidity, provide adequate working space, and achieve a complete resection. This must be performed with minimal manipulation of the neural structures encircling the ventricles, avoiding functional cortical areas, and acquiring early control of feeding vessels [7, 8].

Application of early warning signs to physiological contexts: a comparison of multivariate indices in patients on long-term hemodialysis.

Early warnings signs (EWSs) can anticipate abrupt changes in system state, known as "critical transitions," by detecting dynamic variations, including increases in variance, autocorrelation (AC), and cross-correlation. Numerous EWSs have been proposed; yet no consensus on which perform best exists. Here, we compared 15 multivariate EWSs in time series of 763 hemodialyzed patients, previously shown to present relevant critical transition dynamics. We calculated five EWSs based on AC, six on variance, one on cross-correlation, and three on AC and variance. We assessed their pairwise correlations, trends before death, and mortality predictive power, alone and in combination. Variance-based EWSs showed stronger correlations (r = 0.663 ± 0.222 vs. 0.170 ± 0.205 for AC-based indices) and a steeper increase before death. Two variance-based EWSs yielded HR95 > 9 (HR95 standing for a scale-invariant metric of hazard ratio), but combining them did not improve the area under the receiver-operating curve (AUC) much compared to using them alone (AUC = 0.798 vs. 0.796 and 0.791). Nevertheless, the AUC reached 0.825 when combining 13 indices. While some indicators did not perform overly well alone, their addition to the best performing EWSs increased the predictive power, suggesting that indices combination captures a broader range of dynamic changes occurring within the system. It is unclear whether this added benefit reflects measurement error of a unified phenomenon or heterogeneity in the nature of signals preceding critical transitions. Finally, the modest predictive performance and weak correlations among some indices call into question their validity, at least in this context.

An unusual finding of an anaplastic meningioma in NF2-related schwannomatosis.

NF2-related schwannomatosis (NF2) is a rare autosomal-dominant genetic disorder characterized by bilateral vestibular schwannomas and multiple meningiomas. This case report presents the extremely rare occurrence of an anaplastic meningioma in a 12-year-old male with previously undiagnosed NF2. The patient presented with a history of abdominal pain and episodic emesis, gait unsteadiness, right upper and lower extremity weakness, and facial weakness. He had sensorineural hearing loss and wore bilateral hearing aids. MR imaging revealed a sizable left frontoparietal, dural-based meningioma with heterogeneous enhancement with mass effect on the brain and midline shift. Multiple additional CNS lesions were noted including a homogenous lesion at the level of T5 indicative of compression of the spinal cord. The patient underwent a frontotemporoparietal craniotomy for the removal of his large dural-based meningioma, utilizing neuronavigation and transdural ultrasonography for precise en bloc resection of the mass. Histopathology revealed an anaplastic meningioma, WHO grade 3, characterized by brisk mitotic activity, small-cell changes, high Ki-67 proliferation rate, and significant loss of P16. We report an anaplastic meningioma associated with an underlying diagnosis of NF2 for which we describe clinical and histopathological features.

Validation of biomarkers of aging.

The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.

Rethinking the pros and cons of randomized controlled trials and observational studies in the era of big data and advanced methods: a panel discussion.

Randomized controlled trials (RCTs) have traditionally been considered the gold standard for medical evidence. However, in light of emerging methodologies in data science, many experts question the role of RCTs. Within this context, experts in the USA and Canada came together to debate whether the primacy of RCTs as the gold standard for medical evidence, still holds in light of recent methodological advances in data science and in the era of big data. The purpose of this manuscript, aims to raise awareness of the pros and cons of RCTs and observational studies in order to help guide clinicians, researchers, students, and decision-makers in making informed decisions on the quality of medical evidence to support their work. In particular, new and underappreciated advantages and disadvantages of both designs are contrasted. Innovations taking place in both of these research methodologies, which can blur the lines between the two, are also discussed. Finally, practical guidance for clinicians and future directions in assessing the quality of evidence is offered.

Effect of Extra Virgin Olive Oil on Anthropometric Indices, Inflammatory and Cardiometabolic Markers: a Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: A large body of literature associated extra virgin olive oil (EVOO) consumption with low risk of cardiovascular disease and mortality. However, findings from clinical trials related to EVOO consumption on blood pressure, lipid profile, and anthropometric and inflammation parameters are not univocal. OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the effect of EVOO consumption on cardiometabolic risk factors and inflammatory mediators. METHODS: We searched PubMed/MEDLINE, Scopus, and Cochrane up through 31 March, 2023, without any particular language limitations, in order to identify randomized controlled trials (RCTs) that examined the effects of EVOO consumption on cardiometabolic risk factors, inflammatory mediators, and anthropometric indices. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random-effects modeling. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). RESULTS: Thirty-three trials involving 2020 participants were included. EVOO consumption was associated with a significant decrease in insulin (n = 10; SMD: -0.28; 95% CI: -0.51, -0.05; I2 = 48.57%) and homeostasis model assessment of insulin resistance levels (HOMA-IR) (n = 9; SMD: -0.19; 95% CI: -0.35, -0.03; I2 = 00.00%). This meta-analysis indicated no significant effect of consuming EVOO on fasting blood glucose, triglycerides, total cholesterol, low density lipoproteins, very low density lipoproteins, high density lipoproteins, Apolipoprotein (Apo) A-I and B, lipoprotein a, blood pressure, body mass index, waist circumference, waist to hip ratio, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor α levels (P > 0.05). CONCLUSIONS: The present evidence supports a beneficial effect of EVOO consumption on serum insulin levels and HOMA-IR. However, larger well-designed RCTs are still required to evaluate the effect of EVOO on cardiometabolic risk biomarkers. This study was registered in PROSPERO as CRD42023409125.

Prophylactic removal of a migratory missile from the cerebral ventricles: case report.

BACKGROUND AND IMPORTANCE: Nonpowder firearm injuries to the head pose major health risks, with retained fragments potentially causing harmful sequelae that require neurosurgical intervention. CLINICAL PRESENTATION: We report the case of 2-year-old girl who sustained an accidental gunshot wound to the head. She sustained a penetrating ballistic intracranial injury caused by a BB shot from a rifle. At presentation, she was neurologically intact with a punctate laceration on her left forehead. Head CT demonstrated a small depressed left frontal skull fracture, a small intracerebral hematoma, and a 5-mm metallic bullet fragment in the deep left frontal lobe near the frontal horn of the left lateral ventricle. She was admitted to the hospital and managed nonoperatively with levetiracetam and intravenous antibiotics, and discharged home in good condition. Follow-up CT in 1 week showed slight migration of the metallic bullet fragment to the left, placing it at the anterior horn of the lateral ventricle. Six weeks later, follow-up CT showed migration of the bullet to the temporal horn of the left lateral ventricle. Intraventricular migration of the bullet raised concern that it could move further to obstruct the foramen of Monro or cerebral aqueduct. Therefore, we removed the bullet through a small left temporal craniotomy with image guidance using a microsurgical approach through a translucent tube. CONCLUSION: The authors discuss the rationale and technique for removing a nonpowder firearm bullet that has migrated within the cerebral ventricles.

Relative anemia and perioperative stroke in children with moyamoya.

OBJECTIVES: Surgical revascularization for moyamoya arteriopathy decreases long-term stroke risk but carries a risk of perioperative ischemic complications. We aimed to evaluate modifiable stroke risk factors in children undergoing surgical revascularization for moyamoya. MATERIALS AND METHODS: In this exploratory, single-center, retrospective cohort study, medical records of pediatric patients undergoing surgical revascularization for moyamoya arteriopathy at our center between 2003 and 2021 were reviewed. Candidate modifiable risk factors were analyzed for association with perioperative stroke, defined as ischemic stroke ≤7 days after surgery. RESULTS: We analyzed 53 surgeries, consisting of 39 individual patients undergoing indirect surgical revascularization of 74 hemispheres. Perioperative ischemic stroke occurred following five surgeries (9.4%). There were no instances of hemorrhagic stroke. Larger pre-to-postoperative decreases in hemoglobin (OR 3.90, p=0.017), hematocrit (OR 1.69, p=0.012) and blood urea nitrogen (OR 1.83, p=0.010) were associated with increased risk of perioperative ischemic stroke. Weight-adjusted intraoperative blood loss was not associated with risk of perioperative ischemic stroke (OR 0.94, p=0.796). Among children with sickle cell disease, all of whom underwent exchange transfusion within one week prior to surgery, none experienced perioperative stroke. CONCLUSIONS: Decreases in hemoglobin, hematocrit, and blood urea nitrogen between the preoperative and postoperative periods are associated with increased risk of perioperative stroke. These novel findings suggest that dilutional anemia, possibly due to standardly administered hyperhydration, may increase the risk of perioperative stroke in some children with moyamoya. Further work optimizing both mean arterial pressure and oxygen-carrying capacity in these patients, including consideration of alternative blood transfusion thresholds, is necessary.

Physiological Dysregulation Proceeds and Predicts Health Outcomes Similarly in Chinese and Western Populations.

BACKGROUND: A decade ago, we proposed an index of physiological dysregulation based on Mahalanobis distance (DM) that measures how far from the norm an individual biomarker profile is. While extensive validation has been performed, focus was mostly on Western populations with little comparison to developing countries, particularly at a physiological system level. The degree to which the approach would work in other sociocultural contexts and the similarity of dysregulation signatures across diverse populations are still open questions. METHODS: Using 2 data sets from China and 3 from Western countries (United States, United Kingdom, and Italy), we calculated DM globally and per physiological system. We assessed pairwise correlations among systems, difference with age, prediction of mortality and age-related diseases, and sensitivity to interchanging data sets with one another as the reference in DM calculation. RESULTS: Overall, results were comparable across all data sets. Different physiological systems showed distinct dysregulation processes. Association with age was moderate and often nonlinear, similarly for all populations. Mahalanobis distance predicted most health outcomes, although differently by physiological system. Using a Chinese population as the reference when calculating DM for Western populations, or vice versa, led to similar associations with health outcomes, with a few exceptions. CONCLUSIONS: While small differences were noticeable, they did not systematically emerge between Chinese and Western populations, but rather diffusively across all data sets. These findings suggest that DM presents similar properties, notwithstanding sociocultural backgrounds, and that it is equally effective in capturing the loss of homeostasis that occurs during aging in diverse industrial human populations.

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Challenges and Opportunities for Commercializing Technologies in the Pulmonary Arena: An Official American Thoracic Society Report.

"Translational medicine" has been a buzzword for over two decades. The concept was intended to be lofty, to reflect a new "bench-to-bedside" approach to basic and clinical research that would bridge fields, close gaps, accelerate innovation, and shorten the time and effort it takes to bring novel technologies from basic discovery to clinical application. Has this approach been successful and lived up to its promise? Despite incredible scientific advances and innovations developed within academia, successful clinical translation into real-world solutions has been difficult. This has been particularly challenging within the pulmonary field, because there have been fewer U.S. Food and Drug Administration-approved drugs and higher failure rates for pulmonary therapies than with other common disease areas. The American Thoracic Society convened a working group with the goal of identifying major challenges related to the commercialization of technologies within the pulmonary space and opportunities to enhance this process. A survey was developed and administered to 164 participants within the pulmonary arena. This report provides a summary of these survey results. Importantly, this report identifies a number of poorly recognized challenges that exist in pulmonary academic settings, which likely contribute to diminished efficiency of commercialization efforts, ultimately hindering the rate of successful clinical translation. Because many innovations are initially developed in academic settings, this is a global public health issue that impacts the entire American Thoracic Society community. This report also summarizes key resources and opportunities and provides recommendations to enhance successful commercialization of pulmonary technologies.

Risk of Subdural Hematoma Expansion in Patients With End-Stage Renal Disease: Continuous Venovenous Hemodialysis Versus Intermittent Hemodialysis.

BACKGROUND AND OBJECTIVES: Subdural hematoma (SDH) patients with end-stage renal disease (ESRD) require renal replacement therapy in addition to neurological management. We sought to determine whether continuous venovenous hemodialysis (CVVHD) or intermittent hemodialysis (iHD) is associated with higher rates of SDH re-expansion as well as morbidity and mortality. METHODS: Hemodialysis-dependent patients with ESRD who were discovered to have an SDH were retrospectively identified from 2016 to 2022. Rates of SDH expansion during CVVHD vs iHD were compared. Hemodialysis mode was included in a multivariate logistic regression model to test for independent association with SDH expansion and mortality. RESULTS: A total of 123 hemodialysis-dependent patients with ESRD were discovered to have a concomitant SDH during the period of study. Patients who received CVVHD were on average 10.2 years younger ( P < .001), more likely to have traumatic SDH (47.7% vs 19.0%, P < .001), and more likely to have cirrhosis (25.0% vs 10.1%, P = .029). SDH expansion affecting neurological function occurred more frequently during iHD compared with CVVHD (29.7% vs 12.0%, P = .013). Multivariate logistic regression analysis found that CVVHD was independently associated with decreased risk of SDH affecting neurological function (odds ratio 0.25, 95% CI 0.08-0.65). Among patients who experienced in-hospital mortality or were discharged to hospice, 5% suffered a neurologically devastating SDH expansion while on CVVHD compared with 35% on iHD. CONCLUSION: CVVHD was independently associated with decreased risk of neurologically significant SDH expansion. Therefore, receiving renal replacement therapy through a course of CVVHD may increase SDH stability in patients with ESRD.

Evidence for protein leverage on total energy intake, but not body mass index, in a large cohort of older adults.

BACKGROUND: Protein leverage (PL) is the phenomenon of consuming food until absolute intake of protein approaches a 'target value', such that total energy intake (TEI) varies passively with the ratio of protein: non-protein energy (fat + carbohydrate) in the diet. The PL hypothesis (PLH) suggests that the dilution of protein in energy-dense foods, particularly those rich in carbohydrates and fats, combines with protein leverage to contribute to the global obesity epidemic. Evidence for PL has been reported in younger adults, children and adolescents. This study aimed to test for PL and the protein leverage hypothesis (PLH) in a cohort of older adults. METHODS: We conducted a retrospective analysis of dietary intake in a cohort of 1699 community-dwelling older adults aged 67-84 years from the NuAge cohort. We computed TEI and the energy contribution (EC) from each macronutrient. The strength of leverage of macronutrients was assessed through power functions ( TEI = µ * EC L ). Body mass index (BMI) was calculated, and mixture models were fitted to predict TEI and BMI from macronutrients' ECs. RESULTS: In this cohort of older adults, 53% of individuals had obesity and 1.5% had severe cases. The mean TEI was 7673 kJ and macronutrients' ECs were 50.4%, 33.2% and 16.4%, respectively for carbohydrates, fat, and protein. There was a strong negative association (L = -0.37; p < 0.001) between the protein EC and TEI. Each percent of energy intake from protein reduced TEI by 77 kJ on average, ceteris paribus. However, BMI was unassociated with TEI in this cohort. CONCLUSIONS: Findings indicate clear evidence for PL on TEI, but not on BMI, likely because of aging, body composition, sarcopenia, or protein wasting.

Biomarkers of aging through the life course: A Recent Literature Update.

Purpose of review: The development of biomarkers of aging has greatly advanced epidemiological studies of aging processes. However, much debate remains on the timing of aging onset and the causal relevance of these biomarkers. In this review, we discuss the most recent biomarkers of aging that have been applied across the life course. Recent findings: The most recently developed aging biomarkers that have been applied across the life course can be designated into three categories: epigenetic clocks, epigenetic markers of chronic inflammation, and mitochondrial DNA copy number. While these have been applied at different life stages, the development, validation, and application of these markers has been largely centered on populations of older adults. Few studies have examined trajectories of aging biomarkers across the life course. As the wealth of molecular and biochemical data increases, emerging biomarkers may be able to capture complex and system-specific aging processes. Recently developed biomarkers include novel epigenetic clocks; clocks based on ribosomal DNA, transcriptomic profiles, proteomics, metabolomics, and inflammatory markers; clonal hematopoiesis of indeterminate potential gene mutations; and multi-omics approaches. Summary: Attention should be placed on aging at early and middle life stages to better understand trajectories of aging biomarkers across the life course. Additionally, novel biomarkers will provide greater insight into aging processes. The specific mechanisms of aging reflected by these biomarkers should be considered when interpreting results.

Impact of socioeconomic status and chemotherapy on neurocognitive performance in children with brain tumors.

Background: Although the relationship between radiation and neurocognition has been extensively studied in the pediatric brain tumor population, it is increasingly recognized that neurocognitive impairment is multifactorial. Therefore, we quantified the effect of socioeconomic status (SES) and chemotherapy on neurocognitive impairment and decline post-treatment. Methods: Eligible patients included those diagnosed with a brain tumor at < 22 years of age with ≥1 neurocognitive assessment. Neurocognitive impairment was defined as performance 1.5 standard deviations below the normative mean using age-standardized measures of intellectual function. Neurocognitive decline was defined as a negative slope. Neurocognitive outcomes included Wechsler indices of Full-Scale Intelligence Quotient (IQ). Logistic regression identified variables associated with neurocognitive impairment. Longitudinal data was analyzed using linear mixed models. Results: Eligible patients (n = 152, median age at diagnosis = 9.6 years) had a mean neurocognitive follow-up of 50.2 months. After accounting for age and receipt of craniospinal irradiation, patients with public insurance had 8-fold increased odds of impaired IQ compared to private insurance (odds ratio [OR]: 7.59, P < .001). After accounting for age, change in IQ was associated with chemotherapy use (slope: -0.45 points/year with chemotherapy vs. 0.71 points/year without chemotherapy, P = .012). Conclusions: Public insurance, an indicator of low SES, was associated with post-treatment impairment in IQ, highlighting the need to incorporate SES measures into prospective studies. Chemotherapy was associated with change in IQ. Further work is needed to determine whether impairment associated with low SES is secondary to baseline differences in IQ prior to brain tumor diagnosis, brain tumor/therapy itself, or some combination thereof.

Neuroendoscopy: How We Got Here.

From its inception in ancient Egyptian rituals, neuroendoscopy always promised a minimally invasive route to the cerebrum. Early visionaries, however, hit the proverbial wall of technical development until the 20th century, when new technologies allowed for light to be transmitted across a tube for visualization of intracranial structures. Despite a hiccupping start, with surgical microscopy hampering initial excitement, the development and transformation of neuroendoscopy continued, and today it is a widespread and reliable surgical option for the treatment of numerous varied and complex pathologies.

Biomarkers of aging for the identification and evaluation of longevity interventions.

With the rapid expansion of aging biology research, the identification and evaluation of longevity interventions in humans have become key goals of this field. Biomarkers of aging are critically important tools in achieving these objectives over realistic time frames. However, the current lack of standards and consensus on the properties of a reliable aging biomarker hinders their further development and validation for clinical applications. Here, we advance a framework for the terminology and characterization of biomarkers of aging, including classification and potential clinical use cases. We discuss validation steps and highlight ongoing challenges as potential areas in need of future research. This framework sets the stage for the development of valid biomarkers of aging and their ultimate utilization in clinical trials and practice.