bluuebunny/crossref_metadata_2025_split huggingface dataset:
SYST-33 GENERATION OF ALLOGENEIC CAR-T CIRCUMVENTS FUNCTIONAL DEFICITS IN PATIENT-DERIVED AUTOLOGOUS PRODUCT FOR GLIOBLASTOMA
Authors: Shaikh Muhammad Vaseem , Salim Sabra K , Maich William T , Anand Alisha , Wei Jeffrey , Subapanditha Minomi K , Suk Yujin , Singh Manoj , Tabunshchyk Zoya , Chen Katie , Vora Parvez , Venugopal Chitra , Moffat Jason , Singh Sheila K 
Published: August 2023

Abstract
Glioblastoma (GBM) is the most common malignant brain tumor in adults, with a poor prognosis despite aggressive standard of care. Chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in liquid malignancies, but clinical trials in GBM targeting various tumor antigens have not shown durable clinical benefit. While this may be attributable to various tumor-intrinsic immune evasion strategies characteristic of GBM, little work has assessed whether the issue is due to the quality of the CAR-T treatment itself. Currently, CAR-Ts for clinical studies are manufactured in an autologous setting wherein T-cells are extracted from patients, engineered ex-vivo, and subsequently re-infused back. However, peripheral T-cells taken from untreated GBM patients have demonstrated qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to establish whether CAR-Ts generated from GBM patients would show reduced efficacy in comparison to healthy donors using our previously validated CD133 CAR-T. In this work, we show pre-treatment exhaustion and reduced survival advantage in autologous, patient-derived CD133-targeting CAR-T cell products using an orthotopic xenograft model of human GBM. To overcome the functional and logistical considerations of autologous therapy, we additionally aimed to generate an “off-the-shelf” allogeneic CD133 CAR-T. Using CRISPR gene editing technology, we generated TCR-knockout CAR-T cells with comparable pre-clinical efficacy to our autologous models. Ultimately, this work highlights the need to reassess autologous CAR-T therapy for GBM, and consider allogeneic approaches as biologically-informed therapeutic alternatives.
TIPS-03 A PHASE 1 STUDY OF GALLIUM MALTOLATE (GAM) IN PATIENTS WITH RECURRENT GLIOBLASTOMA (GBM)
Authors: Connelly Jennifer , Schmainda Kathleen , Al-Gizawiy Mona , Santos-Pinhero Fernando , Chitambar Christopher 
Published: August 2023

Abstract
Glioblastoma remains the most aggressive malignant brain tumor with universally poor prognosis. New treatments are needed which target novelpathways. GBM cells have significantly greater requirements for iron and display markedly higher levels of transferrin receptors for iron uptake and ferritin for iron storage than surrounding normal astrocytes. The increased intracellular iron pool drives GBM activity. Previously, we showed that since gallium shares certain chemical properties with iron, it can inhibit malignant cell growth by disrupting tumor iron homeostasis. Recently, we reported that GaM is cytotoxic to GBM cell lines and stem cells but not to microvascular endothelial cells. In rodent orthotopically implanted human GBM xenografts, orally administered GaM reduced tumor volume and prolonged animal survival. These preclinical studies form the basis for our Phase 1 study which evaluates GaM in patients with recurrent GBM. The trial will follow a 3 + 3 phase 1 dose escalation design. Three to six patients at each dose level will receive GaM 500 mg/d, 1000 mg/d, or 1500 mg/day for a minimum of two 28-day cycles. Patients age &gt;= 18 years with histologically confirmed GBM or molecular GBM with recurrent measurable disease are eligible. In the absence of measurable disease, pathologic confirmation of recurrence is required. Primary objectives are to determine a maximum-tolerated dose and recommended Phase 2 dose. Safety/tolerability will be assessed. Secondary objectives include disease assessments and evaluation of PFS and OS. Correlative studies planned are sequential blood levels of gallium, iron, Tf, ferritin, and hepcidin. Available tumor tissues will be examined for the expression iron biomarkers by immunochemistry. The study is currently enrolling. Patients will receive study drug until disease progression, unacceptable adverse events, patient withdrawal, or death. To date, 5 patients received GaM 500 mg/d without DLT and 4 patients started GaM 1000 mg/d.
TIPS-07 LONGITUDINAL CSF PROTEOMICS FOR MONITORING AND PHARMACODYNAMIC BIOMARKER DISCOVERY
Authors: Riviere-Cazaux Cecile , Ikram Samar , Andersen Katherine , Warrington Arthur , Burns Terry 
Published: August 2023

Abstract
Rapid feedback is needed to understand the individualized biological impacts of novel glioma therapies. We are performing glioma biomarker discovery by serial cerebrospinal fluid (CSF) sampling from Ommaya reservoirs or lumbar punctures to determine how the CSF proteome can reveal early longitudinal intelligence regarding glioma status, biology, and therapeutic response. We aimed to leverage access to each patient’s glioma via CSF to identify candidate biomarkers of tumor burden, biology, and therapeutic challenge. Global proteomic CSF analysis was performed via Somalogic– an aptamer-based technology for highly sensitive and specific analysis of over 7,000 proteins. Discovery analysis comprised of the top 500 ranked proteins in the CSF from seven patients with high-grade gliomas versus non-glioma (normal pressure hydrocephalus) controls. The top HGG proteins were then filtered to include only proteins that met two additional criteria of 1) decrease with resection, and 2) increase with recurrence in individual paired patient samples. Additionally, in individual patients for whom serial CSF samples were available, protein fold change lists were created and ranked to determine the most or least differentially abundant proteins between various time points. Proteomic enrichment analysis revealed a conserved HGG CSF proteomic signature defined by 79 proteins, including ones known to be over-expressed in solid tumor malignancies, such as retinoblastoma binding protein 4, heat shock protein 90, and sorcin. The HGG proteomic signature was consistently enriched in an independent validation cohort consisting of 13 gliomas diverse in primary versus recurrent status, subtype, and grade, when compared to independent control CSF samples. Encouragingly, proteins in the HGG signature decreased in two patients following decreased tumor burden from surgical resection. Our preliminary data demonstrate the ability to gain detailed, individualized insights regarding glioma biology, tumor burden, and evolution through global CSF proteomics acquired from longitudinal neurosurgical access to each patient’s unique glioma.
TIPS-12 PHASE I CLINICAL STUDY OF TG02 CAPSULE IN THE TREATMENT OF RECURRENT HIGH-GRADE GLIOMAS WITH FAILED TMZ TREATMENT
Authors: Guo Chengcheng , Yang Qunying , Cao Xi , Liao Yixiang , Li Xiaoyi , Dai Xiangrong , Chen Zhongping 
Published: August 2023

Abstract

BACKGROUND
This study(NCT 03904628) is a dose-escalation, open-label phase I study which enrolled high grade glioma patients who failed with temozolomide(TMZ) treatment. The study purpose is to investigate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of an multi-kinase inhibitor (TG02 capsule, with primary inhibitory effects on cyclin-dependent kinases), as a new therapy for patients with recurrent high-grade glioma patients.

METHODS
The key inclusion criteria were 18-75 years old, glioblastoma or anaplastic astrocytoma confirmed by histology; when disease progression after receiving temozolomide; according to RANO criteria had evaluable lesions; ECOG performance status of 0-2. Eligible patients were enrolled sequentially into different dose groups and received TG02 capsule every 4 weeks .The dose was increased in a traditional 3 + 3 design. Primary endpoints were the dose-limited toxicity (DLT) and the maximum tolerated dose(MTD). Second endpoints were pharmacokinetic characteristics and preliminary efficacy.

RESULTS
Between May 2019 and November 2021, twelve patients were enrolled. No DLT was occurred and MTD was not defined in study. The plasma concentration of TG02 reached the maximum at 2 h after administration, and the elimination half-life was about 7 h. Eleven patients(91.7%) had one or more treatment-related adverse events (TRAEs) assessed using CTCAE 5.0. Most frequent TRAEs were vomiting (91.7%), diarrhea (75.0%), and 50% of the patients had grade 3 or 4 AEs. There were no treatment-related deaths. The median progression-free survival (PFS) was 1.77 months (95%CI:0.82 ~ 4.24). The median OS was 9.63 months (95%CI:2.66 ~ NE).

CONCLUSION
TG02 capsule is safe and tolerable in patients with recurrent high-grade gliomas. Switching to using TG02 capsule showed some patients had intracranial tumor reduction who failed to treat with TMZ. TG02 can be further explored with combined therapy in the treatment of gliomas.
Creatinine to Cystatin-C Ratio in Renal Cell Carcinoma: A Clinically Pragmatic Prognostic Factor and Sarcopenia Biomarker
Authors: Schmeusser Benjamin N , Biermann Henry , Nicaise Edouard H , Ali Adil A , Patil Dattatraya H , Midenberg Eric , Helman Talia , Armas-Phan Manuel , Nabavizadeh Reza , Joshi Shreyas S , Narayan Vikram M , Bilen Mehmet A , Psutka Sarah P , Ogan Kenneth , Master Viraj A 
Published: August 2023

Abstract

Introduction
Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy.

Methods
We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression.

Results
A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia.

Conclusions
Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy.
Effectiveness of Cognitive Functional Therapy Versus Core Exercises and Manual Therapy in Patients With Chronic Low Back Pain After Spinal Surgery: Randomized Controlled Trial
Authors: Avila Leonardo , da Silva Morgana Duarte , Neves Marcos Lisboa , Abreu Andre Rogerio , Fiuza Cibelle Ramos , Fukusawa Leandro , de Sá Ferreira Arthur , Meziat-Filho Ney 
Published: August 2023

Abstract

Objective
Our aim was to investigate whether cognitive functional therapy (CFT) was more effective than core exercises and manual therapy (CORE-MT) in improving pain and function for patients with chronic low back pain after spinal surgery.

Methods
This study was a randomized controlled superiority trial in a university hospital and a private physical therapist clinic in Santa Catarina, Brazil. Eighty participants who were 18 to 75 years old and had chronic low back pain after spinal surgery received 4 to 12 treatment sessions of CFT or CORE-MT once per week for a maximum period of 12 weeks. Primary outcomes were pain intensity (numeric pain rating scale, scored from 0 to 10) and function (Patient-Specific Functional Scale, scored from 0 to 10) after intervention.

Results
We obtained primary outcome data for 75 participants (93.7%). CFT was more effective, with a large effect size, than CORE-MT in reducing pain intensity (mean difference [MD] = 2.42; 95% CI = 1.69–3.14; effect size [d] = 0.85) and improving function (MD = −2.47; 95% CI = −3.08 to −1.87; effect size = 0.95) after intervention (mean = 10.4 weeks [standard deviation = 2.17] after the beginning of treatment). The differences were maintained at 22 weeks for pain intensity (MD = 1.64; 95% CI = 0.98–2.3; effect size = 0.68) and function (MD = −2.01; 95% CI = −2.6 to −1.41; effect size = 0.81).

Conclusion
CFT was more effective than CORE-MT, with large effect sizes, and may be an option for patients with chronic low back pain after spinal surgery.

Impact
CFT reduces pain and improves function, with large effect sizes, compared with CORE-MT. The difference between CFT and CORE-MT was sustained at the midterm follow-up. Treatment with CFT may be an option for patients with chronic low back pain after spinal surgery.
Utility of Negative Pressure Wound Therapy: Raising the Bar in Chest Masculinization Surgery
Authors: Abu El Hawa Areeg A. , Dekker Paige K. , Mizher Rami , Orra Susan , Fan Kenneth L. , Del Corral Gabriel 
Published: August 2023

Background:
Prophylactic use of negative pressure wound therapy (NPWT) has been shown to decrease the incidence of postoperative complications. This study aimed to evaluate the utility of NPWT in chest masculinization with free nipple graft (FNG).

Methods:
All consecutive male patients undergoing chest masculinization with FNG by a single provider at a single center were reviewed. Postoperative treatment with either NPWT or standard wound care (SWC) defined this study’s cohorts. Patient characteristics and postoperative complications were compared between patients receiving NPWT versus SWC.

Results:
One hundred thirty-one patients with 262 closed breast incisions (NPWT=72, SWC=190) met inclusion criteria. Overall complications were higher in the SWC cohort (n=80/190, 42%) compared to the NPWT cohort (n = 13/72, 18%, p < 0.001). The NPWT group had significantly lower rates of partial nipple graft loss (9/72, 12.5% versus 47/190, 24.7%, p = 0.031), seroma formation (1/72, 1.4% versus 15/190, 7.9%, p = 0.037), and nipple hypopigmentation (6/72, 8.3% versus 36/190, 18.9%, p = 0.024) when compared to the SWC cohort. Time to drain removal was significantly faster in the NPWT group (NPWT 7 days versus SWC 9 days, p ≤ 0.001).

Conclusions:
Patients receiving NPWT over their closed incisions following chest masculinization with FNG were found to have significantly lower rates of partial nipple graft necrosis, seroma formation, and time to drain removal compared to those receiving SWC. Future prospective, randomized studies to further elucidate the role of NPWT in top surgery are warranted.
Immediate Skin Replacement Allows for Nipple-sparing, Direct-to-implant Reconstruction in Patients with Advanced Breast Cancers
Authors: Schwartz Jean-Claude D. , Binstock Michael 
Published: August 2023

Summary:
Mastectomy has evolved from approaches that involved extensive skin resection to nipple-sparing mastectomy (NSM). However, patients with advanced breast cancers who require extensive skin resection usually also have their nipple areola complexes (NACs) removed, even if they are distant from the cancer. Implant reconstruction in these patients is challenging as they require tissue expansion and, typically, radiotherapy with additional surgeries to complete their reconstruction. The aesthetic results of this approach are inferior to NSM and direct-to-implant reconstruction. In patients who require significant skin resection but whose NACs are free of tumor, we have found that immediate skin replacement using a muscle-sparing latissimus dorsi flap allows for NSM and direct-to-implant reconstruction, obviating the need for tissue expansion, delayed implant placement, and NAC reconstruction. Here, we report on 12 patients in whom this approach is utilized.
Prepectoral Conversion of Subpectoral Implants for Animation Deformity after Breast Reconstruction: Technique and Experience
Authors: Shikhman Alexander , Erz Logan , Brown Meghan , Wagner Douglas 
Published: August 2023

Background:
Implant-based breast reconstruction in postmastectomy patients is commonly performed in a submuscular plane. Following reconstruction, animation deformity can be a displeasing aesthetic result for patients. In addition, patients may experience more postoperative pain with a submuscular reconstruction. Prepectoral conversion of submuscular implant position is an option for addressing these concerns. We describe a detailed technique and review our results.

Methods:
A retrospective review was conducted of all prepectoral conversions performed by the senior author (DSW) from 2017 to 2019 after IRB approval. All patients presented with animation deformity and another symptom such as asymmetry, pain, and/or capsular contracture. Patients underwent prepectoral conversion with smooth silicone gel implants. Demographic data, outcomes, and patient satisfaction were reviewed.

Results:
Prepectoral conversion was performed in 33 consecutive patients (57 breasts) with animation deformity. Twelve patients had capsular contracture, seven complained of pain, and five had ruptured implants. Postoperative complications included three infections requiring implant removal in two breasts, one implant exposure and one hematoma requiring implant replacement, five seromas requiring aspiration, and one capsular contracture. Seven patients had contour abnormalities addressed with secondary autologous fat grafting. Ultimately, all patients had elimination of animation deformity and were satisfied with the results of the conversion.

Conclusions:
Unsatisfactory results of subpectoral implant reconstruction such as animation deformity and chronic pain have led the reconstructive surgeon to consider various techniques to address these issues. The conversion to a prepectoral plane will effectively eliminate animation deformity, resolve pain, and yield satisfactory results in these patients.
Plastic Surgery Diversity through the Decade: Where We Stand and How We Can Improve
Authors: Hernandez J. Andres , Kloer Carmen I. , Porras Fimbres Denisse , Phillips Brett T. , Cendales Linda C. 
Published: August 2023

Background:
Several studies over the past decade have investigated diversity within the field of plastic surgery, yet it remains unclear if an increase has resulted. This study sought to review the status of diversity within plastic surgery over the last decade and form strategies for residency programs to increase diversity recruitment.

Methods:
Data analysis of racial demographics from the Association of American Medical Colleges databases was completed for all medical students, integrated plastic surgery residency applicants, integrated plastic surgery residents, and academic faculty from 2010 to 2020. Proportional averages were analyzed comparing 5 year durations with heteroscedastic t-tests. Interviews were then conducted with medical school diversity and inclusion officers across the country and subsequent thematic analysis was completed. Finally, diversity recruitment recommendations were synthesized from interview data.

Results:
There was no significant change in demographics of integrated plastic surgery applicants between 2010–2014 and 2015–2020. The only significant finding among integrated plastic surgery residents yielded a reduction in the “Hispanic/ Latino” group (4% -3%, P = 0.01). Faculty data showed an increase in “Hispanic/ Latino” (4% -5%, P < 0.01) and “other” (4% -5%, P = 0.02) groups with a reduction in “White” faculty members (74% -70%, P < 0.01). Final recommendations for diversity recruitment were then formed from diversity and inclusion officer interviews.

Conclusions:
Continuous and sustainable work with respect to diversity and inclusion within plastic surgery has an opportunity for growth. Implementation of key recommendations by residency programs can change the face of our specialty going forward.
Cross-sectional Vascularization Pattern of the Adipofascial Anterolateral Thigh Flap for Application in Tissue-engineered Bone Grafts
Authors: Buergin Joel , Werth Lucas , Largo René , Scherberich Arnaud , Schaefer Dirk J. , Kaempfen Alexandre 
Published: August 2023

Background:
As part of the engineering of bone grafts, wrapping constructs in well-vascularized tissue, such as fascial flaps, improves bone formation. Our aim was to understand the cross-sectional vascularization pattern of human adipofascial flaps for this application.

Methods:
Seven adipofascial anterolateral thigh (ALT) flaps were harvested from five human cadaveric specimens. Axial vessel density was analyzed by immunohistochemistry and quantitative histology.

Results:
We found a high density of blood vessels directly superficial to and close to the fascia. A secondary plexus in between this first suprafascial plexus and the subdermal plexus was also identified. In all specimens, this second plexus showed less vascular density, and appeared to be at a constant level within the suprafascial fat throughout the flaps. The peak measurements for this secondary plexus varied between 1.2 and 2 mm above the deep fascia, depending on the donor’s body mass index.

Conclusions:
Quantitative immunohistochemistry is a reliable method to quantify and locate vessel density in an adipofascial flap. This is vital information before wrapping nonvascularized material into such a flap to estimate the inosculation potential of these vessels and likelihood of survival of the tissue. To profit from both suprafascial vascular plexuses, a correlation between subcutaneous tissue thickness and distance of the second plexus to the fascia should be further investigated. For the moment, we recommend maintaining at least 2–3 mm of subcutaneous fatty tissue on the fascia, to profit from both plexuses. Engineered constructs should be wrapped on the superficial medial side of the fascial flap to enhance vascularization.
The Scratch Collapse Test for Diagnosis and Treatment of Trigger Sites for Migraine Surgery
Authors: Chim Harvey 
Published: August 2023

Summary:
Diagnosis of trigger sites for migraine surgery relies on history to detect a constellation of symptoms and secondarily, nerve blocks, imaging studies, and Doppler probe examination. The scratch collapse test (SCT) has been described for localization of compressive neuropathies in the upper and lower extremities. In this study, we hypothesized that the SCT could also be used to diagnose trigger sites for surgical planning in migraine surgery. Eleven consecutive patients presenting for migraine surgery, and four patients presenting with recurrent headaches and secondary trigger sites after initial successful migraine surgery were examined with the SCT using a standard protocol to assess involvement of bilateral sites I, II, IV, V, and VI, with the carpal tunnel as a negative control. The SCT was positive bilaterally at sites I, II, IV, V, and VI for all patients presenting primarily for migraine surgery, regardless of trigger sites localized by history and other secondary modalities. The SCT, however, correlated with secondary trigger sites localized through history and examination for patients presenting with recurrent migraine headaches after previous primary surgery. The SCT is not reliable for localization of trigger sites in patients presenting primarily for migraine surgery. This likely relates to central sensitization of migraine headaches, leading to global cutaneous allodynia in the head and neck. In patients with recurrent migraine headaches, abrogation of central sensitization following the initial surgery allows diagnosis of secondary trigger sites through the SCT.