Nevin Manimala

J Neurosurg. 2023 Nov 10:1-9. doi: 10.3171/2023.8.JNS23418. Online ahead of print.

ABSTRACT

OBJECTIVE: Arginine vasopressin deficiency (AVD) following neurosurgical procedures for pituitary disorders is common and can delay discharge. Copeptin, a stable surrogate marker of arginine vasopressin, may predict postoperative AVD. The authors’ aim was to assess the optimal postoperative sampling time and cut-point concentration of copeptin to predict the development of postsurgical AVD.

METHODS: Adults without preexisting AVD who were undergoing surgery for a pituitary lesion between February 2020 and April 2022 were eligible for study inclusion. Two samples were drawn from each patient postoperatively to assess the copeptin concentration using an immunofluorescent assay. Samples were denoted as “early” (within 6 hours of extubation) or “postoperative day 1” (POD1; within 10-30 hours of extubation). Patients were evaluated for the development of AVD.

RESULTS: One hundred ninety-two patients (54.2% female) with a median age of 54.5 years (IQR 39.8-67.0 years) were included in the study. The median copeptin concentration at both time points was significantly lower in those with AVD (transient or permanent; n = 22, 11.5%) than in those without (early: 4.9 vs 18.7 pmol/L, p < 0.001; POD1: 3.4 vs 4.9 pmol/L, p < 0.001) but did not differ in those who developed transient versus permanent AVD. The optimal copeptin cut point for the prediction of AVD was < 8.5 pmol/L for early samples (sensitivity 0.70, specificity 0.80, positive predictive value [PPV] 0.29, negative predictive value [NPV] 0.96) and < 4.3 pmol/L for POD1 samples (sensitivity 0.82, specificity 0.63, PPV 0.22, NPV 0.96). In early samples, a copeptin cutoff of 22.9 pmol/L increased the sensitivity for the detection of AVD to 95% with an NPV of 99%. The proportion of patients who had AVD was higher (60.0% vs 8.8%, p < 0.001) and the copeptin concentration lower (early: 4.3 vs 17.0 pmol/L, p < 0.001; POD1: 2.7 vs 4.9 pmol/L, p < 0.001) among those who had undergone surgery for a craniopharyngeal duct pathology versus a pituitary adenoma. Although copeptin was lower in patients with persistent Cushing’s disease than in those in remission, the difference did not reach statistical significance (early p = 0.11, POD1 p = 0.52). Furthermore, the copeptin concentration could not predict the development of syndrome of inappropriate secretion of antidiuretic hormone. Patients without AVD who had received stress dose steroids intraoperatively had lower median early copeptin (11.7 vs 19.1 pmol/L, p = 0.027).

CONCLUSIONS: In early postoperative copeptin samples, the optimal copeptin cut point for AVD diagnosis was < 8.5 pmol/L, and a level > 22.9 pmol/L had predicative utility in excluding AVD. Caution should be used when interpreting copeptin results, as patients administered glucocorticoids intraoperatively without AVD had lower median copeptin concentrations.

PMID:37948691 | DOI:10.3171/2023.8.JNS23418

J Neurosurg Pediatr. 2023 Nov 10:1-12. doi: 10.3171/2023.9.PEDS23117. Online ahead of print.

ABSTRACT

OBJECTIVE: The optimal surgical approach for pediatric craniopharyngiomas (CPs) remains a matter of debate, with selection bias classically precluding a fair comparison of outcomes between the transcranial approach (TCA) and endoscopic endonasal approach (EEA). The purpose of this systematic review was to analyze the current role of EEA in the treatment of pediatric CPs and to determine whether, upon expansion of its indications, a comparison with TCA is valid.

METHODS: A systematic review of English-language articles published between February 2010 and June 2022 was performed to identify studies in the MEDLINE (PubMed) and Embase databases reporting on the resection of pediatric CPs. Included were articles reporting on pediatric CPs removed through TCA or EEA. Case reports, review articles, and earlier or less comprehensive series by the same center were excluded. Baseline characteristics and outcomes were analyzed. Prediction intervals (PIs), heterogeneity (Q, I2, and τ2 statistics), and publication bias (funnel plot analysis) were assessed.

RESULTS: A total of 835 patients underwent TCA (18 articles) and 403 patients underwent EEA (19 articles). Preoperatively, the mean patient age (p = 0.055, PI = 5.05-15.11), visual impairment (p = 0.08, PI = 19.1-90.5, I2 = 80%), and hypothalamic syndrome (p = 0.17, PI = 6.5-52.2, I2 = 62%) did not significantly differ between the EEA and TCA groups. Endocrine deficit (anterior pituitary deficit [p < 0.001, PI = 16.5-92.9, I2 = 81%] and diabetes insipidus [p < 0.001, PI = 6.3-60.6, I2 = 43%]) was more frequent in the EEA group. Hydrocephalus and signs/symptoms of raised intracranial pressure were significantly higher (p < 0.001, PI = 5.2-73.3, I2 = 70% vs p < 0.001, PI = 4.6-73, I2 = 62%, respectively) in the TCA group. Recurrent lesions (p = 0.52, PI = 2.7-87.3, I2 = 13%), tumor size (p = 0.25, PI = 22.1-56.8), third ventricle involvement (p = 0.053, PI = 10.9-81.3, I2 = 69%), and hypothalamic involvement (p = 0.06, PI = 8.5-83.6, I2 = 79%) did not differ significantly between the approaches. EEA was preferred (p = 0.006, PI = 26.8-70.8, I2 = 40%) for sellar-suprasellar CPs, whereas TCA was preferred for purely suprasellar CPs (p = 0.007, PI = 13.5-81.1, I2 = 61%). There was no difference between the approaches for purely intrasellar lesions (p = 0.94, PI = 0-62.7, I2 = 26%). The breadth of PIs, I2 values, and analysis of publication bias showed substantial variability among the pooled data, hindering the possibility of outcome meta-analyses.

CONCLUSIONS: With the adoption of extended approaches, the use of EEA became appropriate for a wider spectrum of pediatric CPs, with associated excellent outcomes. Although a fair comparison between outcomes in the EEA and TCA groups was hindered because of the differences in patient populations and tumor subtypes, given the increased versatility of EEA and improved expertise in its use, surgeons can now select the optimal surgical approach based on the unique benefits and drawbacks of each pediatric CP.

PMID:37948683 | DOI:10.3171/2023.9.PEDS23117

Cereb Cortex. 2023 Nov 8:bhad377. doi: 10.1093/cercor/bhad377. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the effects of peritoneal dialysis and hemodialysis on spontaneous brain activity in patients with end-stage renal disease.

METHODS: A total of 52 dialysis patients with end-stage renal disease, including 25 patients with chronic kidney disease undergoing hemodialysis (HD-CKD) and 27 patients with chronic kidney disease undergoing peritoneal dialysis (PD-CKD), and 49 healthy controls (normal control) were included. All participants underwent neuropsychological testing (Mini-Mental State Examination and Montreal cognitive assessment) and resting-state functional magnetic resonance imaging. Fractional amplitude of low frequency fluctuations and Regional Homogeneity algorithms were employed to evaluate spontaneous brain activity. Statistical analysis was performed to discern differences between the groups.

RESULTS: When compared with the normal control group, the PD-CKD group exhibited significant alterations in fractional amplitude of low frequency fluctuations in various cerebellum regions and other brain areas, while the HD-CKD group showed decreased fractional amplitude of low frequency fluctuations in the bilateral pericalcarine cortex. The Regional Homogeneity values in the PD-CKD group were notably different than those in the normal control group, particularly in regions such as the bilateral caudate nucleus and the right putamen.

CONCLUSION: Both peritoneal dialysis and hemodialysis modalities impact brain activity, but manifest differently in end-stage renal disease patients. Understanding these differences is crucial for optimizing patient care.

PMID:37948670 | DOI:10.1093/cercor/bhad377

Cereb Cortex. 2023 Nov 8:bhad409. doi: 10.1093/cercor/bhad409. Online ahead of print.

ABSTRACT

We utilized motion-corrected diffusion tensor imaging (DTI) to evaluate microstructural changes in healthy fetal brains during the late second and third trimesters. Data were derived from fetal magnetic resonance imaging scans conducted as part of a prospective study spanning from 2013 March to 2019 May. The study included 44 fetuses between the gestational ages (GAs) of 23 and 36 weeks. We reconstructed fetal brain DTI using a motion-tracked slice-to-volume registration framework. Images were segmented into 14 regions of interest (ROIs) through label propagation using a fetal DTI atlas, with expert refinement. Statistical analysis involved assessing changes in fractional anisotropy (FA) and mean diffusivity (MD) throughout gestation using mixed-effects models, and identifying points of change in trajectory for ROIs with nonlinear trends. Results showed significant GA-related changes in FA and MD in all ROIs except in the thalamus’ FA and corpus callosum’s MD. Hemispheric asymmetries were found in the FA of the periventricular white matter (pvWM), intermediate zone, and subplate and in the MD of the ganglionic eminence and pvWM. This study provides valuable insight into the normal patterns of development of MD and FA in the fetal brain. These changes are closely linked with cytoarchitectonic changes and display indications of early functional specialization.

PMID:37948665 | DOI:10.1093/cercor/bhad409

Cereb Cortex. 2023 Nov 8:bhad410. doi: 10.1093/cercor/bhad410. Online ahead of print.

ABSTRACT

Personality traits are commonly regarded as relatively stable, whereas life satisfaction can fluctuate with time and circumstances, shaped by external influences and personal encounters. The correlation between personality traits and life satisfaction is well-established, yet the underlying neural mechanisms of the myelin-based microstructural brain network connecting them remain unclear. Here, we constructed individual-level whole-brain myelin microstructural networks from the MRI data of 1,043 healthy adults and performed correlation analysis to detect significant personality trait-related and life satisfaction-related subnetworks. A mediation analysis was used to verify whether the shared structural basis of personality traits and life satisfaction significantly mediated their association. The results showed that agreeableness positively correlated with life satisfaction. We identified a shared structural basis of the personality trait of agreeableness and life satisfaction. The regions comprising this overlapping network include the superior parietal lobule, inferior parietal lobule, and temporoparietal junction. Moreover, the shared microstructural connections mediate the association between the personality trait of agreeableness and life satisfaction. This large-scale neuroimaging investigation substantiates a mediation framework for understanding the microstructural connections between personality and life satisfaction, offering potential targets for assessment and interventions to promote human well-being.

PMID:37948663 | DOI:10.1093/cercor/bhad410

Am J Manag Care. 2023 Nov 1;29(11):e330-e338. doi: 10.37765/ajmc.2023.89459.

ABSTRACT

OBJECTIVES: To investigate the journey to oral anticoagulant (OAC) access following formulary-related rejection of apixaban (Eliquis) and evaluate characteristics associated with failure to achieve OAC access among patients with atrial fibrillation (AF).

STUDY DESIGN: Retrospective study using the Optum Market Clarity Data from January 2016 through February 2020.

METHODS: Patients had at least 1 claim rejection for apixaban due to prior authorization (PA), formulary exclusion (FE), or quantity limit (QL) and at least 1 AF diagnosis on or before the rejected claim. Descriptive statistics summarized transaction journeys by type of formulary restriction. Multivariable regression assessed patient characteristics associated with not receiving an OAC within 60 days after initial rejection.

RESULTS: Among 18,434 patients in the analytic sample, QL was the most common reason for rejection (68.7%), followed by PA (21.2%) and FE (10.2%). Most patients received a paid OAC claim within 60 days after rejection (82.2%-85.5% across restriction types). Mean time from rejection to paid claim ranged from 5.2 to 10.7 days among patients with a paid OAC claim and 12.4 to 17.6 days among those with multiple attempts before OAC receipt. Characteristics associated with higher odds of not receiving OAC treatment included being male, beingAfrican American, having Medicaid coverage, possessing a high stroke risk score, exhibiting no evidence of prior apixaban treatment, and being prescribed a low dose of apixaban on the initial rejected claim.

CONCLUSIONS: Most patients with a claim rejection for apixaban received approval for apixaban within 60 days, suggesting that initial rejection merely created a delay in treatment. Vulnerable populations were at greater risk of not receiving a paid OAC claim.

PMID:37948653 | DOI:10.37765/ajmc.2023.89459

ACS Chem Biol. 2023 Nov 10. doi: 10.1021/acschembio.3c00440. Online ahead of print.

ABSTRACT

The ellagitannins vescalagin and vescalin, known as actin-dependent inhibitors of osteoclastic bone resorption, were mounted onto chemical probes to explore their interactions with bone cell proteins by means of affinity-based chemoproteomics and bioinformatics. The chemical reactivity of the pyrogallol units of these polyphenols toward oxidation into electrophilic ortho-quinones was exploited using NaIO₄ to promote the covalent capture of target proteins, notably those expressed at lower abundance and those interacting with polyphenols at low-to-moderate levels of affinity. Different assays revealed the multitarget nature of both ellagitannins, with 100-370 statistically significant proteins captured by their corresponding probes. A much higher number of proteins were captured from osteoclasts than from osteoblasts. Bioinformatic analyses unveiled a preference for the capture of proteins having phosphorylated ligands and GTPase regulators and enabled the identification of 33 potential target proteins with systemic relevance to osteoclast differentiation and activity, as well as to the regulation of actin dynamics.

PMID:37948120 | DOI:10.1021/acschembio.3c00440

JMIR Aging. 2023 Nov 10;6:e50345. doi: 10.2196/50345.

ABSTRACT

BACKGROUND: A number of real-world digital literacy training programs exist to support engagement with mobile devices, but these have been understudied.

OBJECTIVE: The purpose of this study was to examine the effectiveness and program acceptability of a digital skills training program among middle-aged and older adults (aged ≥50 years) and to gather participants’ recommendations for lifelong digital skills promotion.

METHODS: The Gluu Essentials digital skills training program includes learning resources to support tablet use. Through pre-post surveys, this study assessed mobile device proficiency, confidence in going online and in avoiding frauds and scams, the frequency of engaging in online activities, program engagement, acceptability, and suggestions for continued support.

RESULTS: A total of 270 middle-aged and older adults completed baseline surveys. Of these 270 participants, 145 (53.7%) completed follow-up surveys. Our findings indicate that mobile device proficiency increased (P<.001), whereas confidence was unchanged. Participants also reported going online more frequently to shop (P=.01) and access government services (P=.02) at follow-up. Program engagement varied considerably, but program acceptability was high. Participants’ recommendations included the need for providing ongoing programs for support and training because technology constantly changes, reducing costs for technology and internet access, and keeping learning resources simple and easy to access.

CONCLUSIONS: The Gluu Essentials digital skills training program increased mobile device proficiency and frequency of web-based activities (shopping and accessing government services) among middle-aged and older adults.

PMID:37948115 | DOI:10.2196/50345

JMIR Res Protoc. 2023 Nov 10;12:e49956. doi: 10.2196/49956.

ABSTRACT

BACKGROUND: Dental fear and anxiety (DFA) is a condition that affects approximately one-quarter of children and adolescents. It is a significant cause for pediatric patients to avoid dental care later in adulthood. Lack of patient cooperation due to DFA can create an environment of stress, often obligating dentists to end appointments prematurely and consider alternative pharmacological treatment options. Virtual reality (VR) use during dental care, providing an immersive experience through sensory stimuli, is potentially an additional nonpharmacologic tool to better manage DFA in children with special health care needs (SHCN) undergoing dental procedures.

OBJECTIVE: This pilot study aims to assess the feasibility and acceptability of VR immersion as a tool to reduce DFA in pediatric special needs patients undergoing dental procedures. The study also aims to gain insight on parent and health care provider perspectives on the use of VR during dental appointments.

METHODS: This pilot randomized controlled trial study will follow a parallel design including 2 groups: a control group (clinic’s standard care using a wall TV) and an experimental group (using a VR game). We will randomize 20 participants to either group. Recruitment will be carried out at the dental clinic of the Centre Hospitalier Universitaire Sainte-Justine, a tertiary-quaternary care center that mostly serves pediatric patients with SHCN. The primary outcome will be patient recruitment rates and completion rates of planned procedures. DFA in children will be assessed using both an observation-based proxy assessment with the Venham Anxiety and Behavior Rating Scale and physiological assessments using parameters such as change in heart rate and levels of salivary alpha-amylase as a stress biomarker before and 10 minutes after the procedure. Sociodemographic characteristics, measures of the levels of parent and health care professional satisfaction, occurrence of side effects, and any deviation from normal procedure length will also be collected. Descriptive statistics, nonparametric tests, and effect sizes will be used for demographic and clinical variables and to present parent and health care professional satisfaction levels as well as procedural time.

RESULTS: This study will be conducted from May 2023 to May 2024, with results expected to be available in December 2024.

CONCLUSIONS: The pilot study will provide insight on the feasibility and acceptability of VR use in clinical dentistry to reduce DFA for pediatric patients with SHCN. This study will guide future research on VR use in pediatric dentistry and can serve as a framework for a larger randomized clinical trial.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05898100; https://classic.clinicaltrials.gov/ct2/show/NCT05898100.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49956.

PMID:37948113 | DOI:10.2196/49956

JMIR Form Res. 2023 Nov 10;7:e45725. doi: 10.2196/45725.

ABSTRACT

BACKGROUND: Transitioning to adulthood and challenges in university life can result in increased stress levels among university students. Chronic and severe stress is associated with deleterious psychological and physiological effects. Digital interventions could succeed in approaching and helping university students who might be at risk; however, the experiences of students with internet-based stress management interventions are insufficiently understood.

OBJECTIVE: This study aims to explore the feasibility; acceptability; and changes in perceived stress, depressive symptoms, and quality of life from baseline to posttest assessment of a 5-session, internet-based stress management intervention guided by an e-coach, developed for university students experiencing high levels of stress.

METHODS: A single-arm study was conducted. Students were recruited from different channels, mainly from a web survey. Students were eligible if they (1) scored ≥20 on the Perceived Stress Scale-10, (2) were aged ≥18 years, and (3) were studying at one of the participating universities. Feasibility and acceptability of the intervention were investigated using several indications, including satisfaction (Client Satisfaction Questionnaire-8) and usability (System Usability Scale-10). We also investigated the indicators of intervention adherence using use metrics (eg, the number of completed sessions). Our secondary goal was to explore the changes in perceived stress (Perceived Stress Scale-10), depressive symptoms (Patient Health Questionnaire-9), and quality of life (EQ-5D-5L scale) from baseline to posttest assessment. In addition, we conducted semistructured interviews with intervention completers and noncompleters to understand user experiences in depth. For all primary outcomes, descriptive statistics were calculated. Changes from baseline to posttest assessment were examined using 2-tailed paired sample t tests or the Wilcoxon signed rank test. Qualitative data were analyzed using thematic analysis.

RESULTS: Of 436 eligible students, 307 (70.4%) students started using the intervention. Overall, 25.7% (79/307) completed the core sessions (ie, sessions 1-3) and posttest assessment. A substantial proportion of the students (228/307, 74.3%) did not complete the core sessions or the posttest assessment. Students who completed the core sessions reported high satisfaction (mean 25.78, SD 3.30) and high usability of the intervention (mean 86.01, SD 10.25). Moreover, this group showed large reductions in perceived stress (Cohen d=0.80) and moderate improvements in depression score (Cohen d=0.47) and quality of life (Cohen d=-0.35) from baseline to posttest assessment. Qualitative findings highlight that several personal and intervention-related factors play a role in user experience.

CONCLUSIONS: The internet-based stress management intervention seems to be feasible, acceptable, and possibly effective for some university students with elevated stress levels. However, given the high dropout rate and qualitative findings, several adjustments in the content and features of the intervention are needed to maximize the user experience and the impact of the intervention.

TRIAL REGISTRATION: Netherlands Trial Register 8686; https://onderzoekmetmensen.nl/nl/trial/20889.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.invent.2021.100369.

PMID:37948106 | DOI:10.2196/45725