bluuebunny/crossref_metadata_2025 huggingface dataset:
QLTI-09. DEFINING GLOBAL BENCHMARK OUTCOMES FOR TRANSSPHENOIDAL SURGERY OF PITUITARY ADENOMAS: A MULTICENTER ANALYSIS OF 2862 CASES
Authors: Drexler Richard , Rotermund Roman , Smith Timothy , Kilgallon John , Honegger Jürgen , Nasi-Kordhishti Isabella , Gardner Paul , Gersey Zachary , Abdallah Hussein , Jane John , Marino Alexandria , Knappe Ulrich , Uksul Nesrin , Rzaev Jamil , Galushko Evgeniy , Gormolysova Ekaterina , Bervitskiy Anatoliy , Schroeder Henry , Eördögh Márton , Losa Marco , Mortini Pietro , Gerlach Rüdiger , Azab Mohammed , Budohoski Karol , Rennert Robert , Karsy Michael , Couldwell William , Antunes Apio , Flitsch Jörg , Ricklefs Franz
Published: November 2022

Benchmarks are important to measure and aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery are not available. Therefore, we aimed to establish robust, standardized outcome benchmarks for transsphenoidal surgery of pituitary adenomas. A total of 2862 transsphenoidal tumor resections from 12 high-volume centers in 4 continents were analyzed. Patients were risk stratified and the median values of each center’s outcomes were established. The outcome benchmark was defined as the 75th percentile of all median values for a particular outcome as defined by Staiger et al. Out of 2862 patients, 1201 (41.9%) defined the benchmark cohort. The proportion of benchmark cases contributing to the final cohort ranged across centers between 22.1% to 59.7%. Within the benchmark cases, 928 (73.3%) patients underwent microscopic (MTS) and 263 (21.9%) patients endoscopic endonasal resection (EES). The overall postoperative complication rate was 18.9% with an in-hospital mortality between 0.0-0.8%. Benchmark cutoffs were ≤ 3.3% for reoperation rate, ≤ 4.6% for cerebrospinal fluid leak requiring intervention, and ≤ 15.3% for transient diabetes insipidus. At 6 months follow-up, benchmark cutoffs were calculated as follows: readmission rate: ≤ 7.1%, new hypopituitarism ≤ 15.5%, new neurological deficit ≤ 1.2%, tumor remnant ≤ 25.5%. This analysis defines benchmark values for transsphenoidal resection of pituitary adenomas targeting morbidity, mortality, surgical and tumor-related outcomes. The benchmark cutoffs can be used to assess different centers, patients’ populations, and novel surgical techniques.
QLTI-18. LIQUID BIOPSY: CLINICALLY INTEGRATED RESEARCH IN THE MODERN PANDEMIC ERA
Authors: Nannapaneni Abhinav , Wigand Amanda , Tundo Kelly , Walbert Tobias , Snyder James
Published: November 2022

The COVID-19 pandemic forced a redesign of clinical research to adapt to an ever-changing situation while minimizing patient and provider risks and preserving scientific discovery. During the initial surge of COVID-19, elective healthcare services and non-critical research operations were halted. These changes inspired dispersed health care operations and streamlined clinical research. The first wave of COVID-19 hit Detroit, Michigan, in March 2020, consuming Henry Ford Health (HFH), in COVID-19 emergency care. HFH has a clinically integrated liquid biopsy (LB) program where enrolled patients provide an LB sample via venipuncture within 7 days of each MRI, typically in the clinic at the point-of-care. Prior to COVID-19, 183 neuro-oncology patients were actively providing LB samples in clinic with a mean of 29.9 specimens monthly. Institutional COVID-19 restrictions on non-critical interactions resulted in months were nearly all outpatient encounters utilized telemedicine and decentralized testing off-site from research operations. This halted LB procurement to 4.55 specimens monthly during early pandemic months. To reduce patient-provider exposure, LB specimens were then procured with the venipuncture for MRI which streamlined LB operations and improved the patient experience. After this change, LB specimen procurement returned to near pre-pandemic levels with a mean of 28.1 monthly specimens, despite a significant population utilizing video visits and imaging at satellite or non-HFH centers. The pandemic forced adaptations to patient encounters that have changed how healthcare is delivered, resulting in parallel changes in research that must be considered in the design of future studies.
QLTI-22. IMPROVING BRAIN CANCER PATIENT ACCESS TO CLINICAL TRIALS ACROSS SEVEN COMMUNITY HOSPITALS, THE PROVIDENCE SOUTHERN CALIFORNIA CLINICAL RESEARCH NETWORK
Authors: Carillo Jose , Wagle Naveed , Sharma Akanksha , Juarez Tiffany , Nguyen Minh , Truong Judy , Byun Timothy , Bott Thomas , Bozoyan Nanor , Park David , Kesari Santosh
Published: November 2022

Despite current FDA approved treatments for glioblastoma (GBM), prognosis remains poor. The rare patient population and limited access to clinical trials are factors in this poor prognosis. Clinical trials need to increase enrollment of patients with glioblastoma and other brain cancers to more rapidly develop more effective treatments. Clinical trials are featured on NCCN guidelines, and are considered “Standard of Care” by many experts. Multiple studies have shown that access to clinical trials is associated with improved survival in GBM, however, less than 25% of patients have access or are offered clinical trials. Access to clinical trials can be even more limited in community hospitals, while a large proportion of brain tumors are treated in smaller centers. Community hospitals care for a significant number of brain tumors annually. We have developed a Clinical Research Network for Neuro-Oncology within the Providence Network involving seven hospitals to date. In the past 3 years, we have grown the number of clinical trials available in outlying cities and counties spanning a distance of 60 miles. Between the seven hospitals in our network, we have 15 clinical trials currently open for brain cancer patients, of which, 3 trials were phase I studies. Over the past 2 years, we have enrolled 104 GBM patients in clinical trials. The ability to enhance access to clinical trials by Neuro-Oncologists treating patients in the community is feasible and promising.
QOL-02. FACTORS INFLUENCING COMPLIANCE IN TTF TREATMENT – THE COMPTUNE STUDY
Authors: Proescholdt Martin , Schmidmeier Melissa , Doenitz Christian , Schmidt Nils-Ole , Mühlberger Andreas
Published: November 2022

INTRODUCTION

Recently, tumor treating fields (TTFields) were established for the treatment of newly diagnosed glioblastoma (nGBM). A crucial parameter for TTFields efficacy is compliance to treatment. In this prospective study, we assessed 5 psychological domains known to influence treatment compliance using a standardized interview in nGBM patients. The results of this psychological assessment were correlated to TTF compliance.

METHODS

A cohort of 49 nGBM patients (female 22; male 27, median age 62 years) were recruited. Most patients received a gross total resection (51%), the postsurgical treatment consisted of concomitant radiochemotherapy plus TTF in most cases (81%), only 2 patients received chemotherapy only, and 7 patients were additionally enrolled in clinical drug trials. The psychological assessment system consisted of 5 domains: Social support, confidence in treatment efficacy, communication status about treatment, anxiety, and depression. The interview was repeated every 8 weeks over a period of 8 months or if patients stopped treatment or developed second tumor progression. Additional phone interviews were conducted every 4 weeks.

RESULTS

Median and mean compliance was 98% and 81.6%, respectively (range 5%-100%), drops of compliance below 75%, which were classified as a threshold value, occurred 2259 times. Over-dispersed Poisson and multivariate negative binomial regression analysis revealed depression to be significantly correlated with the number of drops below 75% and with the mean compliance in the first 4 months of treatment. In addition, at later time points, confidence in treatment efficacy significantly correlated with the number of drops below 75%. All other domains did not appear to be associated with TTF treatment compliance.

CONCLUSION

Overall, compliance to TTF was high, however, drops below 75% of compliance occurred frequently during the measurement periods. In the initial treatment phase, depression was associated with these events, whereas confidence in treatment efficacy was correlated at later time points.
QOL-12. “I’M JUST LIKE A BASKET FULL OF PROBLEMS”: QUALITATIVE STUDY OF COGNITIVE DYSFUNCTION AND QUALITY OF LIFE IN GLIOMA SURVIVORS
Authors: Van Dyk Kathleen , Wall Lucy , Ellingson Benjamin , An Nicholas , Lai Albert , Cloughesy Timothy , Brauer Eden R , Nghiemphu Phioanh L
Published: November 2022

For glioma survivors, cognitive impairment can be a central determinant of quality of life, but we need better understanding of their unique challenges and supportive care needs. In this qualitative study, we aimed to explore the post-treatment experiences of cognitive and functional challenges and their impact on quality of life from the perspectives of glioma survivors. Glioma survivors in an observational study were invited to participate in an in-depth qualitative interview. Using a semi-structured interview guide, interviews were audio-recorded and transcribed verbatim. Data were analyzed using a reflexive thematic analysis approach to develop key themes to inform clinical practice. Participants (n=9) ranged in age from 29 to 72 years, and were at least 4 years post-diagnosis. Under the overarching survivorship theme, three key themes were developed. The first theme, “Learning what my brain can and can’t handle,” centered on functional challenges related to cognitive impairments, including difficulties at work and managing home and family responsibilities. In response, participants described generating their own strategies to manage cognitive limitations in daily activities. The second theme, “Such an important crossroads”, reflected the significant emotional impact of persisting impairments (e.g., frustration, disappointment, reduced self-esteem, acceptance), increased anxiety around an uncertain future, and a shift in personal values towards an increased sense of gratitude, crystalizing of intentions, and focus on things of greatest importance. The final theme, “A solid foundation of people around me”, referred to the necessity of social support, in both emotional and instrumental terms. Many expressed a desire for and appreciation of coping tools and support for the support people in their lives. Nearly all participants expressed interest in cognitive rehabilitation – whether or not they were experiencing significant cognitive problems. These findings have implications for clinical practice and can inform the development of effective patient-centered supportive care interventions in this population.
QOL-20. PATTERNS AND PREDICTORS OF ANXIETY AND DEPRESSION SYMPTOM TRAJECTORIES IN PATIENTS DIAGNOSED WITH PRIMARY BRAIN TUMORS
Authors: Ernster Alayna , Body Anjelica , Deleyrolle Phuong , Clair Jennifer St , Sampson Deborah , Rahman Maryam , Tran David , Mitchell Duane , Ghiaseddin Ashley , Pereira Deidre
Published: November 2022

BACKGROUND

Patients diagnosed with primary brain tumors (pPBTs) exhibit high psychological distress. This study assessed how symptoms of anxiety and depression change over time in pPBTs and identified factors that may predict patients’ symptom trajectories.

METHODS

Ninety-nine adult pPBTs completed psychosocial assessments at routine neuro-oncology clinical appointments over 6 to 18 months, with a minimum 8-week interval between assessments. Symptoms of anxiety and depression were assessed with the PROMIS Anxiety and Depression Short-Forms. The prevalence and incidence of patients with clinically elevated anxiety and depression symptoms throughout follow-up were examined, along with the prevalence of patients that experienced clinically meaningful changes in symptoms between follow-ups. Linear mixed-effects models evaluated changes in symptoms over time at the group level and latent class growth analysis (LCGA) evaluated changes in symptoms over time at the individual level.

RESULTS

At baseline, 51.5% and 32.3% of patients exhibited clinically elevated levels of anxiety and depression, respectively. Of patients with any follow-up data (N = 74), 54.1% and 50% experienced clinically meaningful increases in anxiety and depression scores, respectively. The incidence of moderate to severe anxiety and depression was 15.6% and 8.3%, respectively. There was no significant change in symptoms over time at the group level, but better physical, functional, and brain-cancer well-being predicted significantly lower anxiety and depression symptoms (p< .001). Results from LCGA showcased 5-unique subgroups of patients with distinct anxiety and depression symptom trajectories.

CONCLUSION

pPBTs commonly experience elevated anxiety and depression. Symptoms of anxiety and depression change in clinically meaningful manners throughout the disease, even in the absence of significant group-level time effects. Routine screening for elevated symptoms is needed to capture clinically meaningful changes in symptoms and identify factors affecting symptoms to intervene.
RBIO-01. ACTIVATING AN ION CHANNEL PROMOTES RADIATION-SENSITIZING IMMUNE-DRIVEN ANTI-TUMOR ACTIVITY
Authors: Toukam Donatien Kamdem , Bhattacharya Debanjan , Gawali Vaibhavkumar , Kallay Laura , Karve Aniruddha , Desai Pankaj , Cook James , Ahmed Taukir , Ionascu Trajan Dan , Tridandapani Susheela , Krummel Daniel Pomeranz , Sengupta Soma
Published: November 2022

Standard-of-care for melanoma brain metastases is moving to stereotactic radiosurgery (SRS) with immunotherapy. Although this combined approach shows improved patient survival, the responses are not durable. SRS can also cause adverse reactions such as radiation necrosis, which can result in significant morbidity and even mortality. Lowering SRS dose without negatively impacting its effectiveness would therefore be highly beneficial clinically. Our published data suggests that when treating syngeneic mouse model B16F10 melanoma tumors, the radiation dose can be reduced and its effectiveness can be improved, by activating intrinsic melanoma GABAA receptor (GABAAR) activity using a novel agent, AMLAL-101. This agent acts to enhance GABAAR mediated chloride transport in melanoma cells, which in turn triggers mitochondrial dysregulation associated with tumor regression in mice. While AMLAL-101 alone reduces tumor growth, combining it with radiation results in near complete regression of the irradiated tumor, as well as shrinking of tumor not in the radiation field due to an immune response, i.e., a potent abscopal effect. AMLAL-101 may also function to regulate immune cell infiltration into the tumor microenvironment. Analysis of AMLAL-101 treated tumors show increased infiltration into the tumor microenvironment of: (1) polyfunctional (TNFα/IFN-γ) CD8+ T cells; and (2) tumor-associated macrophages (TAMs) of the tumor inhibitory M1-phenotype, possibly due to IFN-γ stimulation. We posit that activating GABAAR with AMLAL-101 promotes both a ‘direct’ anti-tumor response and an ‘indirect’, immune-driven anti-tumor activity in metastatic melanoma tumors. AMLAL-101 may address an urgent unmet need for a non-toxic therapeutic that can potentiate radiation and mitigate its toxicity profile to positively impact clinical outcomes of patients with brain metastatic disease treated with radiotherapy.
RTID-05. TRIAL IN PROGRESS: DOSE-FINDING STUDY AND EVALUATION OF [177LU]LU-DOTA-TATE IN COMBINATION WITH STANDARD OF CARE IN NEWLY DIAGNOSED GLIOBLASTOMA AND AS A SINGLE AGENT IN RECURRENT GLIOBLASTOMA
Authors: Wen Patrick Y , Cloughesy Timothy , Demange Arnaud , Herrmann Ken , Weller Michael , Zor Evren
Published: November 2022

Patients with glioblastoma have a poor prognosis despite extensive efforts to develop new treatments. Standard of care for newly diagnosed patients is surgery followed by radiotherapy plus temozolomide. However, temozolomide only provides a clinical benefit to patients who have glioblastomas with a methylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promotor. Disease recurrence is inevitable and subsequent treatments have poor outcomes due to limited efficacy and a lack of established therapeutic regimens. [68Ga]Ga-DOTA-TATE is a radioligand imaging agent that selectively binds to somatostatin receptors (SSTRs) and is used with positron emission tomography (PET) for the molecular imaging of SSTR-positive neuroendocrine tumors. Glioblastoma tumoral PET scans have shown moderate uptake of [68Ga]Ga-DOTA-TATE. The radioligand therapy [177Lu]Lu-DOTA-TATE has the same SSTR-targeted ligand and demonstrated promising clinical activity in a pilot study in patients with Grade III/IV gliomas. This Phase 1b open-label dose-finding study (NCT05109728) will determine the recommended [177Lu]Lu-DOTA-TATE dose in three different groups of glioblastoma (newly diagnosed with methylated MGMT promoter [group 1], newly diagnosed with unmethylated MGMT promoter [group 2], and recurrent disease [group 3]). All participants will be scanned with [68Ga]Ga-DOTA-TATE imaging during screening and, for each group, approximately 15 participants will be enrolled in consecutive cohorts of 3–6 participants. All participants will receive up to 6 administrations of [177Lu]Lu-DOTA-TATE (initial dose 150 mCi with 3 provisional dose levels up to 250 mCi) using the Bayesian Optimal Interval design. Group 1 will receive [177Lu]Lu-DOTA-TATE every 4 weeks with concomitant radiotherapy and temozolomide, followed by temozolomide maintenance. Group 2 will receive [177Lu]Lu-DOTA-TATE every 4 weeks for 3 doses with radiotherapy then every 3 weeks as a single agent. Group 3 will receive [177Lu]Lu-DOTA-TATE only, every 3 weeks. The primary endpoint is incidence of dose limiting toxicity. Secondary endpoints include overall objective status (modified RANO criteria), progression free survival, overall survival and safety.
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

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 > 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

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< 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

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 > 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

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

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 >20% on HRCT. In the univariate analysis, longer disease duration (>2.37 years), ILD extent >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

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

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.
Increasing Use Of Interferon Gamma Release Assays Among Children ≥2 Years of Age in a Setting With Low Tuberculosis Prevalence
Authors: Campbell Jeffrey I. , Tabatneck Mary , Sun Mingwei , He Wei , Musinguzi Nicholas , Hedt-Gauthier Bethany , Lamb Gabriella S. , Goldmann Don , Sabharwal Vishakha , Sandora Thomas J. , Haberer Jessica E.
Published: November 2022

US guidelines recommend interferon gamma release assays (IGRAs) for diagnosis of tuberculosis infection in children. In this retrospective cohort study, IGRA use in children 2–17 years of age increased substantially between 2015 and 2021. Testing in inpatient/subspecialty settings (vs. primary care), public (vs. private) insurance, lower age and non-English preferred language were associated with increased odds of receiving an IGRA.
Fatal Early-onset Sepsis Caused by Intrauterine Transmission of Serogroup Y Meningococcus
Authors: Achten Niek B. , Been Jasper V. , Schoenmakers Sam , Vermont Clementien L. , Verdijk Robert M. , Reiss Irwin K. M. , Taal H. Rob
Published: November 2022

Infections by meningococcal species are extremely rare in the first days of life. We present a fatal case of early-onset sepsis presenting at birth, caused by intrauterine transmission of serogroup Y N. meningitidis, evidenced clinically and histologically by corresponding chorioamnionitis and N. meningitidis-positive amniotic fluid. This case confirms a long-standing suspicion that N. meningitidis can be transmitted in utero.
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

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.
DEXMEDETOMIDINE PREVENTS PDIA3 DECREASE BY ACTIVATING α2-ADRENERGIC RECEPTOR TO ALLEVIATE INTESTINAL I/R IN MICE
Authors: Zhan YaQing , Chen ZhaoRong , Qiu YuXin , Deng Qiwen , Huang WenQi , Wen ShiHong , Shen JianTong
Published: November 2022

Background: Dexmedetomidine (DEX) attenuates intestinal I/R injury, but its mechanism of action remains to be further elucidated. Protein disulfide isomerase A3 (PDIA3) has been reported as a therapeutic protein for the prevention and treatment of intestinal I/R injury. This study was to investigate whether PDIA3 is involved in intestinal protection of DEX and explore the underlying mechanisms. Methods: The potential involvement of PDIA3 in DEX attenuation of intestinal I/R injury was tested in PDIA3 Flox/Flox mice and PDIA3 conditional knockout (cKO) in intestinal epithelium mice subjected to 45 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Furthermore, the α2-adrenergic receptor (α2-AR) antagonist, yohimbine, was administered in wild-type C57BL/6N mice intestinal I/R model to investigate the role of α2-AR in the intestinal protection conferred by DEX. Results: In the present study, we identified intestinal I/R-induced obvious inflammation, endoplasmic reticulum (ER) stress-dependent apoptosis, and oxidative stress, and all the aforementioned changes were improved by the administration of DEX. PDIA3 cKO in the intestinal epithelium have reversed the protective effects of DEX. Moreover, yohimbine also reversed the intestinal protection of DEX and downregulated the messenger RNA and protein levels of PDIA3. Conclusion: DEX prevents PDIA3 decrease by activating α2-AR to inhibit intestinal I/R-induced inflammation, ER stress-dependent apoptosis, and oxidative stress in mice.
Efficacy and Safety of Small Bowel Submucosal Tumors Treated by Endoscopic Submucosal Dissection or Endoscopic Full-thickness Resection During Single-balloon Enteroscopy: Prospective Data From a Single-center Study: [RETRACTED]
Authors: Wu Jinqing , Yang Xiaofeng , Wang Guizhou
Published: November 2022

Background and Objectives:

Single-balloon enteroscopy (SBE) is a safe and effective modality for the diagnosis and therapeutic treatment of small bowel disorders. However, the efficacy and safety of treating small bowel submucosal tumors (SMTs) with endoscopic submucosal dissection (ESD) or endoscopic full-thickness resection (EFTR) during SBE have not been determined. Hence, the primary aim of this study was to prospectively evaluate the therapeutic yield of SBE in patients with SMTs.

Patients and Methods:

Twenty-one patients with SMTs were enrolled in this study. Regarding the sex distribution, there were 12 men (57.1%) and 9 women (42.9%). Regarding the age distribution, 42.9% of the patients were 60 years old or older and 57.1% of the patients were under 60 years old. The preoperative characteristics of SMTs were summarized and analyzed, the complete resection incidence of SMTs was determined, and the incidence of postoperative complications was collected. ESD-related and EFTR-related complications and the duration of follow-up after leaving hospital were also summarized and analyzed. The efficacy and safety of SMTs treated by ESD or EFTR during SBE were calculated as percentages.

Results:

Among the 21 patients, 10 (47.6%) underwent EFTR and 11 (52.4%) underwent ESD. The mean diameter of SMTs was 113.50 mm (range: 80 to 160 mm). Anterograde and retrograde SBE were conducted in 11 and 10 patients, respectively. The mean follow-up time was 49.3 days (range: 6.0 to 129 d). The complete resection rate of SMTs was 100%. The complete suture rate of SMTs wound was 100%. The SMTs pathology of all patients showed that the margin-negative (R0) resection was 100%. The incidence of physical discomfort complications (ie, infection/fever, abdominal pain, and abdominal distension) of ESD and EFTR was 5 (23.8%) on day 1, 1 (4.8%) on day 2, and 1 (4.8%) on day 3 after operation. Only 1 (4.8%) patient with EFTR had abdominal pain on the sixth day after leaving hospital, and the visual analog scale/score was 1 point, meaning the pain was easily tolerated by the patient. Twenty (95.2%) patients had no abdominal discomfort after leaving hospital. No patients needed additional surgery because of complications after ESD or EFTR during SBE.

Conclusions:

This preliminary study showed that SMTs can be safely and effectively treated by ESD or EFTR during SBE, particularly SMTs <160 mm in diameter.