bluuebunny/crossref_metadata_2025_split huggingface dataset:
SURG-20. PREOPERATIVE QUANTITATION OF UNRESECTABLE TUMOR VOLUME USING WHOLE-BRAIN TRACTOGRAPHY TO IMPROVE OUTCOME PREDICTION AFTER SURGERY FOR HIGH-GRADE DIFFUSE GLIOMAS
Authors: Ronk Halle , Cheung William , Seenarine Nitish , Yong Raymund 
Published: November 2022

Abstract

BACKGROUND
Because minimizing injury to critical brain regions during high-grade glioma (HGG) surgery is essential, the optimal extent of resection (EOR) for any given patient is often less than 100% of the tumor bulk. However, there are no accepted methods of assessing the upper limit of EOR. Advances in whole-brain tractography (WBT) present an opportunity to address this problem. Here, we develop a predictive model for surgical outcomes in HGG as classified by WHO CNS5, and leverage it to determine the added utility of a WBT-based volumetric resectability metric.

METHODS
We included patients who underwent biopsy or resection of a new or recurrent HGG by the senior author from 2013 to 2020. A volumetric tumor analysis method incorporating WBT was developed to calculate EOR and unresectable tumor volume (UTV). Using perioperative clinical data, multiple linear and Cox regression models were used to identify independent predictors of EOR and progression-free survival (PFS).

RESULTS
A total of 151 HGGs were included. Median EOR and PFS were 97.0% and 5.0 months, respectively. Greater EOR strongly predicted longer PFS overall (hazard ratio [HR]=0.21, 95% confidence interval [CI] 0.07-0.72), with the largest PFS benefit observed at &gt; 85% EOR. When controlling for EOR, higher residual tumor volume (RTV) predicted longer PFS (HR=0.97, 95% CI 0.94-0.99), suggesting the existence of an RTV threshold below which PFS decreases. Involvement of eloquent regions (p=0.0086) and brainstem (p=0.0006) as categorical variables predicted lower EOR but failed to predict shorter PFS. Calculation of UTV based on actual or imputed WBT data was feasible and reliably predicted EOR.

CONCLUSION
Existing methods of measuring HGG resectability are poorly reproducible and do not independently predict survival. Preoperative measurement of WBT-based UTV, by substituting for EOR, may simplify and improve HGG outcome prediction, allowing neurosurgeons to better assess the surgical candidacy of individual patients.
SURG-24. QUANTITATIVE ANALYSIS OF TUMOR CELL DENSITY AND PROTOPORPHYRIN IX FLOURESCENCE IN GLIOMA PATIENTS USING PAIRED STIMULATED RAMAN HISTOLOGY AND TWO-PHOTON EXCITATION FLUORESCENCE MICROSCOPY
Authors: Nasir-Moin Mustafa , Wadiura Lisa Irina , Juros Devin , Movahed-Ezazi Misha , Lee Matthew , Weiss Hannah , Müther Michael , Alber Daniel , Ratna Sujay , Fang Camila , Suero-Molina Eric , Hellwig Sönke , Stummer Walter , Rössler Karl , Hainfellner Johannes , Widhalm Georg , Kiesel Barbara , Reichert David , Mischkulnig Mario , Jain Rajan , Trautman Jay , Pastore Steve , Pacione Donato , Placantonakis Dimitris , Oermann Eric , Golfinos John , Hollon Todd , Snuderl Matija , Freudiger Christian , Orringer Daniel 
Published: November 2022

Abstract
Fluorescence guidance is widely utilized to improve the precision of cancer surgery. 5-aminolevulinic acid, the most widely used fluorophore in glioma surgery, is thought to cause selective accumulation of fluorescent protoporphyrin IX (PpIX) in tumor cells by exploiting pathologic alterations in heme biosynthetic pathways. PpIX-induced fluorescence is highly specific for densely tumor-infiltrated tissue but less effective for visualizing the tumor periphery. To improve clinical detection of PpIX, we developed a microscope to perform paired stimulated Raman histology and two-photon excitation fluorescence microscopy (TPEF) and validated it in 175 fresh, unprocessed core tumor specimens from 75 high-grade glioma patients and three central nervous system lymphoma patients across three institutions. Surprisingly, intracellular PpIX accumulation was observed primarily in cells with histiocytic, rather than neoplastic morphology, and the number of cells concentrating PpIX within the cytoplasm was associated with the abundance of CD163 positive cells (p&lt; 0.02). There was no correlation between the degree of tumor cellularity and the concentration of PpIX across all imaged specimens (R=-0.21). Our findings encourage reconsideration of the existing theory of 5-ALA-induced tumor cell fluorescence in gliomas and demonstrate how 5-ALA and TPEF imaging can provide a window into the immune microenvironment of human gliomas.
SURG-34. INTRAOPERATIVE CORTICOBULBAR MOTOR EVOKED POTENTIALS RELIABLY PREDICT FACIAL NERVE FUNCTION IN ELDERLY PATIENTS WITH CEREBELLOPONTINE ANGLE TUMORS. A CLINICAL AND NEUROPHYSIOLOGY STUDY
Authors: Della Pepa Giuseppe M , Stifano Vito , D'Alessandris Quintino Giorgio , Menna Grazia , Burattini Benedetta , Domenico Michele Di , Izzo Alessandro , D'Ercole Manuela , Bonaventura Rina Di , Lauretti Liverana , Olivi Alessandro , Montano Nicola 
Published: November 2022

Abstract

BACKGROUND
Cerebellopontine angle (CPA) surgery for extra-axial lesions in elderly patients could be hampered by concerns regarding functional outcomes. However, an overall ageing society warrants an improved approach. Intraoperative neuromonitoring is crucial for facial nerve (FN) preservation: intraoperative cortico-bulbar facial motor evoked potentials (FMEPs) can be effectively coupled to standard techniques. In a previous work, we validated the use of FMEPs as preditors of early and late post-operative FN function (FNF). Aim of this study was to re-evaluate FMEP role in patients beyond 65 years of age.

METHODS
An institutional series of 83 patients was reported. A pair of needle electrodes was used to record FMEP from orbicularis oculi (OOc) and orbicularis oris (OOr) muscles; baseline, final and minimum values were recorded. From FMEP amplitudes, minimum-to-baseline (MBR) and final-to-baseline (FBR) amplitude ratios, and recovery value (RV=FBR-MBR), were calculated. These indices were correlated to early (at discharge) and late (at 1-year) post-operative FNF.

RESULTS
23 (27.7%) patients were older than 65 years. Among these, 52.2% and 81% had a good early and late FNF, respectively. Early and late FNF were not associated to age (p &gt; 0.99 and p=0.72, respectively). In elderly patients, higher FBR (from OOc and OOr) and MBR (from OOc) were associated to a good early FN recovery (p=0.01, p=0.009, and p=0.03, respectively). Conversely, MBR from OOr was the only parameter significantly associated with late FN function (p=0.049). ROC analysis confirmed that, in elderly patients, the most accurate index for predicting late FN function was MBR as measured from OOr (AUC=0.869, cut-off value 12.5%). The most accurate index for predicting early FN function was FBR from OOc (AUC=0.865).

CONCLUSION
Cortico-bulbar FMEPs are reliable predictors of early and late post-operative FNF in elderly patients and allow a safe and feasible surgery in this important cohort.
COVID-19 Vaccines and the Virtues
Authors: Boyneburgk Konrad v , Bellazzi Francesca 
Published: November 2022

Abstract
From a moral point of view, what arguments are there for and against seeking COVID-19 vaccination? Can it be morally permissible to require (parts of) a population to receive a vaccine? The present paper adopts a perspective of virtue ethics and argues both that it is morally right for an individual virtuous moral agent to seek COVID-19 vaccination and for a virtuous ruler to impose mandatory vaccinations on her population.
We begin by first presenting virtue ethics and the current vaccine controversy. Second, we examine whether a virtuous individual should get vaccinated. Third, we consider whether, from a moral point of view, it is right for a ruler to impose mandatory vaccinations on her citizens. Fourth, we answer some objections to our argument. Finally, we conclude that virtue ethical considerations warrant both the individual choice of getting vaccinated and mandatory vaccinations against COVID-19.
Risk factors for lung function decline in systemic sclerosis-associated interstitial lung disease in a large single-centre cohort
Authors: Ramahi Ahmad , Lescoat Alain , Roofeh David , Nagaraja Vivek , Namas Rajaie , Huang Suiyuan , Varga John , O’Dwyer David , Wang Bonnie , Flaherty Kevin , Kazerooni Ella , Khanna Dinesh 
Published: November 2022

Abstract

Objectives
The aim of this study was to identify risk factors of percent predicted forced vital capacity (ppFVC) decline in patients with SSc-associated interstitial lung disease (SSc-ILD).

Methods
We identified 484 patients with SSc who had HRCT Chest, of which 312 with ILD. Those with serial pulmonary function tests were included in a longitudinal analysis (n = 184). Linear mixed effect models were fitted to assess the decline in ppFVC over time, and to explore the effect of demographics and baseline characteristics on ppFVC decline.

Results
The majority of SSc-ILD patients were female (76.3%) and 51.3% had diffuse cutaneous subset. The mean (s.d.) age was 53.6 (12.7) years, median disease duration since first non-RP symptoms was 2.6 years, and 48.4% of the patients had ILD extent &gt;20% on HRCT. In the univariate analysis, longer disease duration (&gt;2.37 years), ILD extent &gt;20%, and anti-topoisomerase I (ATA) positivity were significantly associated with ppFVC decline. In the multivariate analysis, the only statistically significant variable associated with ppFVC decline was ATA positivity. The overall group’s mean decline in ppFVC was –0.28% (P-value 0.029), with –0.13% (n = 163) in those who were alive and –8.28% (P-value 0.0002 for the change in ppFVC trajectory) in patients who died within 2 years.

Conclusion
Our study confirms that ppFVC is a marker of survival in SSc-ILD, supporting its use for risk stratification to identify patients who may benefit from earlier interventions and treatment. Our study also supports the role of ATA positivity as a predictive marker for ppFVC decline in this population.
Atherogenic indices in pediatric population in South-Southeast region of Mexico
Authors: Gómez-Pérez Samuel , Ovando-Gómez Valeria , Hernández-Contreras Armando Camilo , Herón-Petri Marcelo , Díaz-López Héctor Ochoa , García-Miranda Rosario , Irecta-Nájera César Antonio 
Published: November 2022

Abstract

Background
Atherosclerosis is a cardiovascular disease, highly predictable, and associated with different atherogenic indices (AI) in adults. However, such indexes in the pediatric population are far less explored. The objective of this study was to evaluate the AI and the cardiovascular factors in the pediatric population in the South-Southeast of México.

Methods
A total of 481 children between 2 and 17 years old were recruited. Anthropometric evaluation, blood pressure (BP), lipid profile, apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) were measured, and AI were calculated. The population was grouped by age, binary logistic regression analysis was performed to analysis for associations of AI and cardiovascular risk factors. Sensibility and specificity of AI to detect metabolic alteration were evaluated for curve ROC.

Results
The atherogenic risk presented a high prevalence in the pediatric population, such as LDL-c/ApoB (86.9%), AIP (78%) and AC (36.6%). Preschoolers showed a higher risk of ApoB/ApoA-I and ApoB/LDL-c, while adolescents have a high risk of AIP. CRI-I and AC were associated with elements of lipid profile and body mass index (BMI). ROC curves analysis shows that AIP is the best index evaluating metabolic syndrome (MS) (0.87) and dyslipidemia (0.91).

Conclusion
Such pediatric population showed a high risk of AI, mainly by LDL-c/ApoB and AIP. The BMI was the cardiovascular risk factors most frequently related to AI, AIP is the best index for detecting cases of MS and dyslipidemia. This is the first study carried out in the pediatric population from the South-Southeast of Mexico that evaluated the AI.
Combining Shelf Osteotomy With Proximal Femoral Reconstruction After Oncologic Resection
Authors: Zhou Joanne Y. , Lai Cara , Pun Stephanie Y. , Richey Ann , Leshikar Holly B. , Avedian Raffi , Steffner Robert 
Published: November 2022

Introduction:
Oncologic proximal femoral resection and reconstruction in skeletally immature children remains a formidable task due to the risk of developing hip instability with patient growth or interval leg lengthening through the prosthesis. Shelf pelvic osteotomy increases femoral head coverage and containment, and favorable long-term results have been reported in the setting of developmental dysplasia of the hip and Perthes disease. We present a technique of combining shelf osteotomy with expandable proximal femoral endoprosthesis reconstruction in pediatric limb-sparing surgery.

Materials and Methods:
Four surgeons at 2 centers from 2012 to 2020 performed proximal femoral reconstruction with shelf osteotomy. Data were collected retrospectively on operative technique, radiographic measurements, and complications including dislocation, subluxation, implant loosening, pain, function, and radiographic outcomes.

Results:
Five patients were included in the study. The mean follow-up was 49 months (range: 17 to 104 mo). The mean lateral center edge angle status postproximal femoral resection and reconstruction shelf osteotomy was 56.1 degrees (±30.5). There were no reported incidences of subluxations, dislocations, periprosthetic fractures, or soft tissue complications. The 3 patients with the longest follow-up at 3, 5, and 8 years tolerated serial lengthening of the endoprosthesis totaling 1 cm, 7.25 cm, and 9 cm, respectively, and demonstrated earlier triradiate cartilage closure in the operative side compared with the nonoperative side. All patients have returned to independent ambulation.

Discussion:
Combining proximal femoral reconstruction with shelf osteotomy in limb salvage pediatric orthopedic oncology may help to improve hip stability with serial lengthening and patient growth.
Impact of organic anion transporting polypeptide, P-glycoprotein, and breast cancer resistance protein transporters on observed tamoxifen and endoxifen concentration and adverse effects
Authors: Keller Denise N. , Medwid Samantha J. , Ross Cameron D. , Wigle Theodore J. , Kim Richard B. 
Published: November 2022

Objective
Drug transporters are important determinants of drug disposition and response. Tamoxifen is an antiestrogen for breast cancer therapy known for adverse drug reactions (ADRs). In this study, the involvement of OATP transporters in tamoxifen and endoxifen transport was studied in vitro while the impact of single nucleotide variation (SNV) in OATP and efflux transporters P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) on ADRs during tamoxifen therapy were assessed.

Methods
Patients receiving tamoxifen for breast cancer, who were CYP2D6 normal metabolizers were enrolled (n = 296). Patients completed a survey that captured ADRs and a blood sample was collected. Tamoxifen and endoxifen plasma concentration were measured, while DNA was genotyped for SNVs in ABCB1, ABCG2, SLCO1A2, SLCO1B1, and SLCO2B1. HEK293T cells were used to determine the extent of OATP-mediated transport of tamoxifen and endoxifen.

Results
Common SNVs of ABCB1, ABCG2, SLCO1A2, and SLCO1B1 were not associated with tamoxifen or endoxifen concentration. However, tamoxifen concentration was significantly higher in carriers of SLCO2B1 c.935G>A (129.8 ng/mL) compared to wildtype (114.9 ng/mL; P = 0.036). Interestingly, subjects who carried SLCO1A2 c.38A>G reported significantly less dizziness (P = 0.016). In-vitro analysis demonstrated increased cellular accumulation of tamoxifen in cells overexpressing OATP1A2 and 1B1, but endoxifen uptake was not effected in OATP overexpressing cells.

Conclusions
We showed that OATP1A2, a transporter known to be expressed at the blood-brain barrier, is capable of tamoxifen transport. Additionally, OATP1A2 c.38A>G was associated with reduced ADRs. Taken together, our findings suggest genetic variation in OATP transporters may be an important predictor of tamoxifen ADRs.
The Impact of Antiviral Resistance on Herpetic Keratitis
Authors: Moshirfar Majid , Kelkar Neil , Peterson Telyn , Bradshaw Justin , Parker Lawsen , Ronquillo Yasmyne C. , Hoopes Phillip C. 
Published: November 2022

Abstract:
Herpes simplex keratitis resistance to antiviral treatment presents a growing concern. The herpes simplex virus has many different mechanisms of resistance to antiviral treatment, which have been well described. Resistance to acyclovir occurs because of mutations in the viral thymidylate kinase and DNA polymerase that decrease this enzyme's affinity for its substrate. This article discusses factors that explain the prevalence of this resistance, the ability for recurrences in immunocompromised populations, current treatments for acyclovir-resistant herpes simplex keratitis, and novel therapies for this growing concern.
A Systematic Review to Evaluate a Possible Association Between Congenital Toxoplasmosis and Preterm Labor
Authors: Mejia Maria C. , Cardenas Maria C. , Narasimhan Ramya , Littlefield Dawn , Enninga Elizabeth Ann L. , Chakraborty Rana 
Published: November 2022

Background:
Congenital toxoplasmosis (CT) is a widespread infection in several countries, and it is defined as an infection of a fetus, newborn, or infant under 1 year of age. Moreover, it represents a thread to pregnant women globally. The objective of our study is to evaluate a potential association between prematurity and CT and whether intrauterine transmission impacts gestational length during pregnancy.

Methods:
PubMed, Cochrane Library and Google Scholar databases were searched from 1950 to 2019. Case–control studies, retrospective, and prospective cohort studies were eligible. Seven studies were included from a total of 314. The Newcastle–Ottawa scale was used to establish the quality of the articles included.

Results:
Based on our review, an association between CT and preterm labor was not established, which may reflect heterogeneity in screening, treatments administered, and differing reported incidences of CT across continents over 69 years. A multicenter prospective cohort study powered to investigate a potential association is indicated.

Conclusion:
Further studies are needed including multicenter prospective cohort studies powered to investigate key clinical associations such as vertical transmission and preterm birth.
Subjective and Objective Taste Change After Stapes Surgery Systematic Review and Meta-Analysis
Authors: Coelho Daniel H. , Lee Seong , Yang Edward , Carli Matthew 
Published: November 2022

Abstract

Introduction
Iatrogenic injury to the chorda tympani (CT) is a well recognized, although potentially underestimated, consequence of stapes surgery. This study aims to review the currently available literature to determine the incidence and prognosis of taste disturbances in these patients.

Data Sources
PubMed, Embase, and Cochrane Library databases

Methods
Databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Search terms included (chorda tympani OR gustatory OR taste OR chemosensory OR dysgeusia OR nervus intermedius) AND (ear surgery OR middle ear OR stapes OR stapedectomy OR stapedotomy). Patients with prospective data collection including preoperative data were further divided by methodology into “objective” and “subjective” assessments of taste dysfunction. A systematic review was performed for all included studies, with meta-analysis using a random-effects model was used for those with comparable methodology and patient populations.

Results
Initial search yielded 2,959 articles that were screened according to inclusion and exclusion criteria. Once duplicates were removed, seven studies were identified, representing 173 patients with subjective testing (all seven studies) and 146 with objective testing (five studies). Eighty of 173 patients (46.2%) noted a disturbance in taste at early follow-up, whereas as 26 of 173 (15.0%) noted long-term problems. Objective methodology and result reporting were heterogenous and not amenable to pooled meta-analysis for all studies included.

Conclusion
Changes in taste occur relatively frequently after stapedectomy. Surgeons should continue to counsel prospective patients as to the risks of both short- and long-term taste disturbances.
A Study to Evaluate the Effectiveness of “Mindfulness-Based Stress Reduction Therapy(MBSRT)” in Reducing Symptom Severity and Improving Quality of Life in Patients Suffering From Irritable Bowel Syndrome
Authors: Ashraf M. Uwais , Akhouri Deoshree , Bhardwaj Divyashish , Siddiqui Bushra 
Published: November 2022

Introduction:
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with a high prevalence. IBS is considered a disorder of brain-gut interaction. Mindfulness-Based Stress Reduction Therapy (MBSRT) is a form of treatment that uses meditation and relaxation to foster awareness and acceptance of the present moment. This kind of therapy requires individuals to practice noticing and observing details about their surroundings without passing judgment or reacting to triggers in the environment.

Material and Methods:
After making the diagnosis of IBS, 30 patients were subjected to concomitant MBSRT in addition to pharmacological therapy(Case Group) while the remaining were given only pharmacotherapy (Control Group). MBSRT was performed by a Clinical Psychologist. Seventeen patients were given only pharmacological therapy (Control Group). Scores were assessed using the IBS Symptom Severity Scale (IBS-SSS), Five Facets of Mindfulness Questionnaire(FFMQ), and World Health Organisation Quality Of Life-BREF (WHO-QOL-BREF) before and after the completion of MBSRT sessions.

Results:
The study included 47 patients (30 in the case group and 17 in the control group) who presented to Medicine OPD and were diagnosed with IBS. Kendall tau correlation test was applied for IBS-SSS scores, which showed significant improvement in IBS-SSS scores postmindfulness therapy in the case group with P value of <0.001. McNemar test was applied for FFMQ scores, which showed significant improvement in FFMQ scores postmindfulness therapy in the case group with a P value of <0.001. A logistic regression model was also generated, which showed a significant change in QOL scores after MBSRT.

Conclusion:
IBS patients who received MBSRT had a greater improvement in the quality of life and mindfulness components and reduced IBS symptoms as compared with the control group.