bluuebunny/crossref_metadata_2025 huggingface dataset:
CLRM-10 ENHANCED PATIENT CARE FOR BRAIN METASTASIS PATIENTS UTILIZING A DEDICATED METASTASIS TUMOR BOARD
Authors: Rogers Lisa , Robin Adam , Shah Mira , Siddiqui Salim , Snyder Jim , Walbert Tobias , Lee Ian , MIkkelsen Tom , Rock Jack , Scarpace Lisa
Published: August 2023

BACKGROUND

Patients with brain metastases are a heterogeneous population. In contrast to patients with primary brain tumors, these patients require individualized therapy based on the type and status of systemic cancer, number and volume of brain metastases, anticipated efficacy of therapy and survival. Therapeutic options for brain metastasis; surgical, radiation and precision medicine approaches have increased in recent years as has survival for a number of cancers, leading to more sophisticated care. To meet this challenge in January 2023 we organized a dedicated brain metastasis tumor board.

METHODS

We reviewed the number of total patients, and those newly-diagnosed, presented at the dedicated brain metastasis board in the first 10 weeks of 2023 as compared with the same time interval the prior year where similar cases were presented at a general brain tumor board. We also assessed change in practice pattern based on the dedicated metastasis tumor board.

RESULTS

89 patients were presented in the first 10 weeks of 2023, including 75 who were newly diagnosed. The total number and those newly diagnosed are 17% higher than the prior year. The dedicated brain metastasis board, staffed by experts in brain metastases, allowed for earlier identification of patients eligible for clinical trial and additionally our review of patients identified the need for standardizing advanced imaging techniques including high resolution, higher contrast-dose MRI scans for better assessment of brain metastases across our hospital sites.

CONCLUSION

We found that a dedicated brain metastasis board increased the number of patients presented for multidisciplinary review, including new patients, which served to better identify those eligible for clinical trial. It led to a consensus to incorporate advanced imaging techniques for assessing treatment response. The experience is superior to inclusion of these patients in a general brain tumor board.
LMAP-14 EFFECT OF TRANSLATIONAL VARIATION ON DOSE CHANGE ADOPTED FOR CONE-BEAM CT GUIDED FRAME BASED STEREOTACTIC RADIOSURGERY OF BRAIN TUMORS
Authors: Anbumani Silambarasan , Noid George , Puckett Lindsay , Straza Michael , Schultz Christopher , Bovi Joseph
Published: August 2023

INTRODUCTION

Gamma knife (GK) is a highly precise form of stereotactic radiosurgery (SRS) that delivers high doses of radiation to small, well-defined targets in a variety of tumor and vascular abnormalities. In some frame-based cases, a small translation can occur between the planning MRI and the cone-beam CT acquired at the time of treatment. Measuring the effect of patient translation on the dose distribution may be useful for informing clinical decisions. Materials/

METHODS

This retrospective study of 113 planning target volumes (PTV) from 33 patients investigates the effect of translational variation on dose metrics recalculated based on cone-beam CT guided for frame based GK radiosurgery. The approved dose adjustments after the original treatment plan in terms of change in mean dose and dose coverage were compared with corresponding translation variation and the volume of PTV. The magnitude of translational variation was compared with the change in dose distribution.

RESULTS

We observed about 53% of cases have at least 0.1 Gy to max 1.2 Gy change in mean dose approved for the translation variation of patients while about 20% of cases have dose coverage fraction change in the range of 2-10%. Furthermore, the change in mean dose and coverage fraction is not linear with the translation variation, but a significant number of dose changes is observed when the variation magnitude is >0.5 mm. PTV volume varied between 0.04 to 22 cm3 and the dose change has been most often adopted when the volume is <2.5 cm3 and the change increases for the decreasing PTV volume.

CONCLUSION

This work provides new insights identifying the suitable tolerance level for translational variations of patients and the resulting impact on the prescribed dose for frame-based SRS.
LMAP-21 PRELIMINARY CLINICAL DATA IN THE PHASE 1/2A DOSE ESCALATION TRIAL OF RHENIUM (186RE) OBISBEMEDA (186RNL) IN LEPTOMENINGEAL METASTASES (LM): THE RESPECT-LM TRIAL
Authors: Youssef Michael , Bao Ande , Phillips William , Hedrick Marc , Moore Melissa , LaFrance Norman , Patel Toral , Floyd John , Brenner Andrew , Michalek Joel
Published: August 2023

OBJECTIVES

Leptomeningeal metastases (LM) are an increasing complication of metastatic cancer with limited treatment options and poor survival. 186RNL is BMEDA-chelated 186Re encapsulated in nanoliposomes. 186Re’s ~2 mm beta emission path length provides direct delivery of radiation therapy while sparing surrounding healthy tissue. A Phase I dose escalation safety and efficacy study (ReSPECT-LM, NCT05034497) is current enrolling.

METHODS

ReSPECT-LM is a multi-center, sequential cohort, open-label, dose-escalation, Phase 1/2a clinical trial in adults evaluating the safety, tolerability, and activity of a single dose of 186RNL given via Ommaya reservoir. The primary objectives are maximum tolerated dose, safety, progression, and survival. Using a modified 3x3 Fibonacci design, increasing doses were administered in 5 mL followed by whole body planar and SPECT/CT imaging for dosimetry and distribution. CSF tumor cell count/mL using microfluidic chamber assay was assessed up to 56 days.

RESULTS

A total of 7 LM patients have been treated (3 male, 4 female) with metastatic oropharyngeal, breast, and lung cancer. One patient was treated twice (retreatment). 186RNL showed prompt, complete distribution throughout the CSF with durable retention in the subarachnoid space and leptomeninges. Absorbed doses ≥20 Gy to the ventricles and cranial subarachnoid spaces were measured. In patients positive for CSF tumor cells, a decrease in counts ranging from 50-92% was observed. Six patients remain alive, while 1 patient has died due to primary tumor progression. No patients had treatment related adverse events (AEs) greater than Grade 1, and the most common AE was headache.

CONCLUSION

Preliminary, interim results of this ongoing study showed that a single treatment with 186RNL delivered by an intraventricular catheter is well tolerated, without dose limiting toxicity and with decreased CSF tumor cell counts durable through at least 30 days. Enrollment and dose escalation is continuing, and repeated dosing will be further explored.
NEIM-01 IMMUNOSUPPRESSION IN THE GLIOMA MICROENVIRONMENT: USING PET IMAGING TO HIGHLIGHT THE PRESENCE OF TIGIT
Authors: Frederico Stephen , Vincze Sarah , Nisnboym Michal , Li Bo , Sneiderman Chaim , Server ReidAnn , Day Kathryn , LaToche Joseph , Nedrow Jessie , Edwards Wilson , Kohanbash Gary
Published: August 2023

Malignant gliomas are one of the drivers of brain tumor patient mortality as these tumors respond poorly to conventional therapies and are known to grow aggressively. Many clinical trials have evaluated the efficacy of novel immuno-therapeutics targeted to gliomas; however, these trials have largely been unsuccessful. It is believed that one of the primary reasons immunotherapies have been unsuccessful in gliomas is due to the highly immunosuppressive nature of the tumor microenvironment. T cell immunoreceptor with Ig and ITIM domain (TIGIT) is an IC receptor that is expressed on activated T cells, Natural Killer (NK) cells, and Regulatory T cells (Tregs). It has been well established that TIGIT has a primary role in down-regulating T cell and NK cell function and can serve as an inhibitor of anti-tumor immune responses. Our laboratory and others have shown that anti-TIGIT therapy may be promising for the treatment of adult gliomas via glioma patient transcriptomic data and preclinical models. In this study, our team created a radiolabeled tracer (referred to as 89Zr-DFO-TIGIT) that bound TIGIT antigen with moderate immunoreactivity (57.7% ± 3.5%). Binding affinity was determined by performing bead-based immunoreactivity assays. To create 89Zr-DFO-TIGIT, a TIGIT monoclonal antibody was conjugated to the metal chelator DFO and radiolabeled with 89Zr. Following tracer preparation, glioma-bearing mice (GL261 cell line) were injected with 89Zr-DFO-TIGIT allowing for the visualization of TIGIT in the tumor microenvironment. PET imaging analyses revealed tracer-to-tumor uptake that increased from day one to day eight while biodistribution studies confirmed that there were significantly higher amounts of 89Zr-DFO-TIGIT detected in the glioma-bearing mouse brain hemisphere compared to the non-tumor bearing hemisphere. We now intend to evaluate 89Zr-DFO-TIGIT in a glioma-bearing large animal model to determine if this method demonstrates similar efficacy in visualizing immunosuppression in the tumor microenvironment before proceeding to clinical studies.
SDPS-22 THE CLINICAL OUTCOMES OF ATYPICAL TERATOID/RHABDOID TUMOR FROM ONE SINGLE CLINICAL CENTER
Authors: Li Juan , Ai Ruyu , Lai Mingyao , Hu Qingjun , Cai Linbo
Published: August 2023

BACKGROUND

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive tumor that occurs most commonly in infants and young children. The prognosis for patients with AT/RT is generally poor, with a five-year survival rate of less than 30%.

METHODS

We retrospectively analyzed the clinical data of patients with AT/RT in the past 10 years at the Guangdong Sanjiu Brain Hospital

RESULTS

A total of 18 cases (male/female = 9:9; median age at diagnosis, 3.5 years (range 1-58 years old)) were diagnosed with AT/RT between 2017 and 2023. AT/RT had higher prevalence in children < 36 months (55.6%), and at infratentorial (66.7%). The median follow-up time was 15.5 months, with a range of 2-62 months. Survival analyses demonstrated that patients > 3 years of age (n = 9 (50%)) had median survival time 28months and patients ≤ 3 years of age (n = 9 (50%)) had median- survival time 15 months (p =0.034) The average survival time for disseminated tumor was 15 months, and for patients with localizedtumors was 44 months. (P=0.012)

CONCLUSION

Older age, localized tumor improves the survival of patients with AT/RT.
SDPS-23 CUMULATIVE TUMOR VOLUME THRESHOLD CORRELATES WITH NEUROCOGNITIVE IMPAIRMENT IN PATIENTS WITH NEWLY DIAGNOSED BRAIN METASTASES
Authors: Zhen Junjie , Cao Xiangyi , Wen Lei , Wang Hui , Lai Mingyao , Cai Linbo
Published: August 2023

OBJECTIVE

To explore the basic situation of cognitive function in patients with initial state of brain metastasis and the potential factors affecting cognitive function, so as to find the critical value of cumulative tumor volume leading to cognitive dysfunction.

METHODS

A total of 284 patients who were newly diagnosed with brain metastases and underwent cognitive testing before radiotherapy in Guangdong Sanjiu Brain Hospital from 2016 to 2022 were retrospectively analyzed. The basic demographic information of the patients, KPS at the time of initial diagnosis, the number of brain metastases, the cumulative tumor volume, and the cognitive function test data before treatment were organized.

RESULTS

The cognitive impairment occurred in 100/284 patients (the criteria for cognitive impairment is that at least two of the eight sub-tests are less than 1.5 standard deviation or at least one is less than 2 standard deviations). Multivariate analysis showed that the number of tumors was not a factor in cognitive dysfunction. Age, gender, KPS, educational level, and cumulative tumor volume were risk factors affecting cognitive function. The cumulative tumor volume cut-off value for MOCA, HVLT-R immediate memory, HVLT-R delayed memory, VFT, TMT-A, and TMT-B cognitive impairment were 13.608, 13.125, 11.070, 14.523, 11.070, and 11.113 cc, respectively, while cut-off value for SDMT and TOL were 5.435 and 4.528 cc, respectively.

CONCLUSIONS

Before treatment, cognitive impairment of brain metastases had no significant correlation with the number of metastases but had a significant correlation with the cumulative tumor volume. The cumulative tumor volume cut-off value involving overall cognitive dysfunction, memory dysfunction, speech dysfunction, and decreased thinking speed is between 11-14.5 cc, and the cumulative tumor volume critical threshold involving executive dysfunction and computational dysfunction is between 4.5-5.5 cc.
SPCR-06 FINANCIAL AID REQUESTS BY BRAIN TUMOR PATIENTS IN ONTARIO THROUGH GOFUNDM
Authors: Devaraja Kaviya , iyengar Yajur , Zhang Andy , Avery Jonathan , Climans Seth
Published: August 2023

OBJECTIVE/PURPOSE

Ontario brain tumor patients sometimes suffer the burden of responsibility to pay for treatments like oral chemotherapy. However, less is known about other direct and indirect financial costs due to their diagnosis. The purpose of this study was to analyze publicly-available data from GoFundMe, an online fundraising platform, to explore the financial needs of brain tumor patients.

METHOD

A qualitative descriptive design drawing on thematic analysis was used to analyze GoFundMe requests to support individuals diagnosed with brain cancer in Ontario between 2014 and 2021. A coding framework was created to determine emerging themes using qualitative data analysis software NVivo 10.

RESULTS

There were 195 fundraising requests. Requests described financial strain from the loss of income experienced by the patient and their caregivers to afford cancer treatments. Requests highlighted 1) an overall lack of awareness of how and where to access financial aid and affordable psychosocial support; 2) concerns over the long-term financial well-being of bereaving family members; 3) A call for more public awareness of the financial burden and emotional distress experienced by of those impacted by brain cancer.

CONCLUSIONS/CLINICAL IMPLICATIONS

These GoFundMe requests highlight a connection between financial burden and emotional distress and an overall lack of awareness of where/how to seek financial and emotional support. These results will serve as the foundation to advocate for and raise awareness of the financial assistance needed by brain tumor patients and their families.
SYST-22 INTEGRATING GENE DEPENDENCY INTO A PEDIATRIC-FOCUSED CANCER DATA PORTAL FOR TARGETED THERAPY AND BIOMARKER DISCOVERY
Authors: Sun Claire , Ajith Vikesh , Panday Monty , Firestein Ron
Published: August 2023

Pediatric solid cancers, particularly those affecting the central nervous system (CNS), are the leading cause of disease-related deaths in children. Despite significant efforts to sequence pediatric solid tumors, they exhibit a "quiescent genome" with a considerably lower mutational burden than adult cancers. This leads to fewer actionable drug targets and poor response to cancer immunotherapy agents, including checkpoint inhibitors. As a result, it is imperative to move beyond genetic alterations and adopt a combination of functional and integrative approaches to develop novel, targeted treatments that are specifically designed for pediatric cancers. Over the past five years, the Next-Gen Precision Medicine Program team has devoted its efforts to establishing the Childhood Cancer Model Atlas (CCMA) (Sun, Daniel et al. Cancer Cell 2023). The CCMA is the largest collection of high-risk pediatric solid tumor cell lines globally, presenting a tremendous opportunity to integrate molecular features with functional dependencies using state-of-the-art computational approaches. However, the analysis of -omics level data is often limited to laboratories with specialized bioinformatics capabilities. Therefore, the establishment of the CCMA data portal with user-friendly analytical and visualization capabilities is essential to accelerate data-driven discovery and translational research in pediatric cancer on a global scale. The data portal is designed to simplify reporting, automate manual processes, and enhance the quality, usability, and longevity of the CCMA dataset. Its highlighted features concentrate on customized analysis, informative results, and user-friendly data visualization. Furthermore, by connecting the established models and their original tumor with clinical and molecular endpoints, the data portal enables clinical integration within the Australian molecular tumor board framework. This analytical data portal will enable the generation of new research hypotheses, prioritizes therapeutic opportunities, and supports international collaborative efforts in pediatric cancer.
SYST-25 MICROGLIA-SECRETED LIPID SPECIES DRIVE GLIOMA INVASION
Authors: Pallares-Moratalla Carla , Guyot Mélanie , Weng Linqian , Planque Melanie , Fendt Sarah-Maria , Swinnen Johan , Lambrechts Diether , Bergers Gabriele
Published: August 2023

The capacity of gliomas, including GBMs, to invade and infiltrate normal brain tissues makes their complete surgical removal impossible. The most crucial survival predictor is still the extent of surgical resection, urging the need to identify treatments that block the invasive growth of glioma to improve surgical resection and overall survival. Using a combination of single-cell transcriptomics, lipidomics, and high-resolution spatial metabolomics in genetically engineered GBM mouse models, reminiscent of human disease, and validation in human GBM samples, we found that 1) tumor cells infiltrating the normal brain parenchyma associate with and activate specific pathways in microglial cells (MGs), the residential brain macrophages. In turn, MGs undergo metabolic rewiring and secrete lipid species that promote glioma invasion of the different GBM subtypes by activating distinct signaling cues. Thus, blocking the MG-tumor cell axis or metabolic MG rewiring targets several GBM types and, in combination with standard therapy, results in small circumscribed tumors that should be easier excised and lead to a substantial increase in progression-free survival in glioma patients.
Impact of E-liquid Packaging on Vaping Product Perceptions Among Youth in England, Canada, and the United States: A Randomized Online Experiment
Authors: Simonavičius Erikas , East Katherine , Taylor Eve , Nottage Matilda , Reid Jessica L , Arnott Deborah , Bunce Laura , McNeill Ann , Hammond David
Published: August 2023

Introduction

Vaping is not risk-free but can help those who smoke to reduce harm to health and stop smoking. However, packaging of vaping products, including e-liquids, appeals to youth and might facilitate vaping among nicotine-naïve people. Standardized packaging of vaping products could moderate the appeal of vaping among youth. This study assessed how youth interest in trying and perceived health harms of using e-liquids are associated with branded or standardized (white or olive) e-liquid packaging with different nicotine levels displayed.

Aims and Methods

A between-subject experiment with three packaging and two nicotine level conditions included youth (n = 13801) aged 16 to 19 from England, Canada, and the United States as a part of a cross-sectional online survey in August–September 2021. Participants’ interest in trying and perceived harm of e-liquids were analyzed using logistic and multinomial regressions adjusted for age, sex, race or ethnicity, country, vaping, and smoking status.

Results

Compared with branded e-liquid packs, more youth reported no interest in trying e-liquids in white (aOR = 1.48, 95% CI = 1.34 to 1.64) or olive (aOR = 1.62, 95% CI: 1.47 to 1.80) standardized packs. Compared with branded e-liquid packs, more youth inaccurately perceived e-liquids in white (aOR = 1.22, 95% CI: 1.11 to 1.34) or olive (aOR = 1.29, 95% CI: 1.18 to 1.41) standardized packs as equally or more harmful than smoking. E-liquid nicotine levels displayed on packs were not associated with youth interest in trying or harm perceptions of using e-liquids.

Conclusions

Among 16- to 19-year-old youth from England, Canada, and the United States, standardized packaging of e-liquids was associated with lower interest in trying and higher health risk perceptions.

Implications

Branded packaging of vaping products appeal to youth and might prompt nicotine use among those who had never smoked. This study suggests that restricting branding elements on e-liquid packaging is associated with youth's lower interest in trying e-liquids and higher misperceptions that vaping is equally or more harmful than smoking. Standardized packaging might reduce appeal of vaping among youth, but its potential to discourage vaping for harm reduction should also be considered.
Charitable donations to natural disasters: evidence from an online platform
Authors: Jayaraman Rajshri , Kaiser Michael , Teirlinck Marrit
Published: August 2023

We investigate the demand and supply of charitable donations to natural disasters on a large online platform. We document that the bulk of charitable donations goes to a tiny fraction of natural disasters, which tend to be severe disasters that receive media coverage. Charities do not fundraise for the remaining 96% of disasters, which account for 80% of casualties. Using an event study-type design to explore temporal patterns in charitable donations, we find that fundraising and giving for disaster relief occur in a timely fashion, but that both are effectively absent for disasters that occur within a 2-month window of large disasters which have attracted massive funding. We also find no evidence that donations to disasters crowd out those to other charitable causes.
Plastid Nucleoids: Insights into Their Shape and Dynamics
Authors: Nishimura Yoshiki
Published: August 2023

Chloroplasts/plastids are unique organelles found in plant cells and some algae and are responsible for performing essential functions such as photosynthesis. The plastid genome, consisting of circular and linear DNA molecules, is packaged and organized into specialized structures called nucleoids. The composition and dynamics of these nucleoids have been the subject of intense research, as they are critical for proper plastid functions and development. In this mini-review, recent advances in understanding the organization and regulation of plastid nucleoids are overviewed, with a focus on the various proteins and factors that regulate the shape and dynamics of nucleoids, including DNA-binding proteins and membrane anchorage proteins. The dynamic nature of nucleoid organization, which is influenced by a variety of developmental cues and the cell cycle, is also examined.
A brief review of contrastive learning applied to astrophysics
Authors: Huertas-Company Marc , Sarmiento Regina , Knapen Johan H
Published: August 2023

Reliable tools to extract patterns from high-dimensionality spaces are becoming more necessary as astronomical data sets increase both in volume and complexity. Contrastive Learning is a self-supervised machine learning algorithm that extracts informative measurements from multidimensional data sets, which has become increasingly popular in the computer vision and Machine Learning communities in recent years. To do so, it maximizes the agreement between the information extracted from augmented versions of the same input data, making the final representation invariant to the applied transformations. Contrastive Learning is particularly useful in astronomy for removing known instrumental effects and for performing supervised classifications and regressions with a limited amount of available labels, showing a promising avenue towards Foundation Models. This short review paper briefly summarizes the main concepts behind contrastive learning and reviews the first promising applications to astronomy. We include some practical recommendations on which applications are particularly attractive for contrastive learning.
Targeting B cells for treatment of systemic sclerosis
Authors: Terui Hitoshi , Segawa Yuichiro , Asano Yoshihide
Published: August 2023

Purpose of review

The pathogenesis of systemic sclerosis (SSc) has been linked to dysfunctional B cells as demonstrated in previous research. This review aims to show the evidence and ongoing clinical trials of B cell-targeted therapy and overview the various aspects of B cell involvement in SSc.

Recent findings

We provide an overview of the current understanding and therapeutic strategies targeting B cells in SSc patients. Several molecular targets of B cells have been identified for treating SSc, including CD20, CD19, B-cell activating factor (BAFF), and proteasome.

Many clinical trials have demonstrated that B cells play a critical role in the pathogenesis of SSc and may be a potential therapeutic target to improve disease symptoms. Although large-scale clinical studies are needed, various B cell-targeted therapies have the potential to address the unmet needs of SSc patients.
Comparison of clinical features and outcomes of proliferative, fibrotic, and mixed subtypes of IgG4-related disease: A retrospective cohort study
Authors: Peng Linyi , Zhang Xinlu , Zhou Jiaxin , Li Jieqiong , Liu Zheng , Lu Hui , Peng Yu , Fei Yunyun , Zhao Yan , Zeng Xiaofeng , Zhang Wen
Published: August 2023

Background:

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes.

Methods:

We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis.

Results:

We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils (P = 0.010), total IgE (P = 0.006), high-sensitivity C-reactive protein (P <0.001), erythrocyte sedimentation rate (P <0.001), complement C4 (P <0.001), IgG (P = 0.001), IgG1 (P <0.001), IgG4 (P <0.001), and IgA (P <0.001), at baseline were significantly different among three subtypes. Compared with proliferative and mixed subtypes, the fibrotic subtype showed the lowest rate of relapse (log-rank P = 0.014).

Conclusions:

Our study revealed the differences in demographic characteristics, clinical manifestations, organ involvement, laboratory tests, treatment agents, and outcomes across proliferative, fibrotic, and mixed subtypes in the retrospective cohort study. Given significant differences in relapse-free survival among the three subtypes, treatment regimens, and follow-up frequency should be considered separately according to different subtypes.
Free Flap Surgery Outcome Related to Antithrombotic Treatment Regime: An Analysis of 1000 Cases
Authors: Jakobsson Stina , Kamali Alexander , Edsander Nord Åsa , Sommar Pehr , Halle Martin
Published: August 2023

Background:

Autologous free tissue transfer is today an integral part of reconstructive plastic surgery, but still lacks generally accepted guidelines regarding antithrombotic agents. We hypothesized that the overuse of antithrombotic agents could be a risk factor for free flap complications and therefore studied a treatment protocol adjustment.

Methods:

Consecutive free flaps between 2005 and 2020 at a single center were analyzed for complications in relation to the use of pre- and intraoperative treatment with three different antithrombotic agents. The use of preoperative low molecular weight heparin (LMWH), intraoperative heparin, and dextran were analyzed in relation to outcome variables, thromboembolic events, or reexploration for hematoma.

Results:

Nine hundred thirty-one patients underwent 1000 microvascular free flaps for breast (n = 487), head and neck (n = 365), and extremity (n = 148) reconstruction. Within the first postoperative week, 44 cases had a thromboembolic event and 58 cases underwent hematoma-related reexploration. In the multivariate analysis, thromboembolic events were associated with extremity reconstruction (P = 0.02) and smoking (P = 0.02). Hematoma-related reexploration was more common with triple antithrombotic therapy compared with all other treatment regimes (P < 0.05). The number of antithrombotic agents used perioperatively was linearly decreased, from three to none, over the elapsed time period (P < 0.001).

Conclusions:

Hematoma was the most common reason for reexploration and was further associated with the use of multiple antithrombotic agents. Cessation of triple treatment was associated with less hematomas and further reduction of antithrombotic agents did not result in any increase of thromboembolic events. Evidence-based guidelines are warranted for antithrombotic regimes in standard free flap surgery.
Does Initial Cleft Lip Width Predict Final Aesthetic Outcome?
Authors: Yang Jenny F. , Smetona John , Lopez Joseph , Peck Connor , Pourtaheri Navid , Steinbacher Derek M.
Published: August 2023

Background:

A natural aesthetic appearance of the lip and a favorable scar are essential goals of cleft lip repair. Wider clefts intuitively pose a greater technical challenge; however, the relationship between initial width and aesthetic outcome remains controversial. The current study aimed to determine whether lip adhesion can help wider clefts achieve safe, consistent aesthetic outcomes.

Methods:

A retrospective cohort study was conducted on unilateral cleft lip patients who underwent lip repair within a 2-year period by the senior author. Subjects were divided into three groups based on cleft severity: (1) wide complete clefts that required lip adhesion before definitive repair, (2) narrower complete clefts that did not require lip adhesion, and (3) incomplete clefts. Aesthetic outcomes related to the vermillion and upper lip scar were rated by 48 blinded observers. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney tests. Nasal outcomes were not assessed.

Results:

Seventeen patients were included in the study: five in group 1, six in group 2, and six in group 3. Patients with the widest clefts did not have inferior results compared with the other groups. In fact, they had statistically significantly higher aesthetic scores in all scar-related outcomes compared with those in groups 2 and 3 (P < 0.0001).

Conclusions:

This study suggests that a wide cleft does not necessarily foreshadow a poor surgical outcome. In fact, wide clefts may have pleasing results, and the use of a staged lip adhesion approach can be useful for achieving the desired outcome in wider clefts.
Practical Review on Delayed Primary Closure: Basic Science and Clinical Applications
Authors: ElHawary Hassan , Covone Jason , Abdulkarim Shafic , Janis Jeffrey E.
Published: August 2023

Wound healing complications present a significant burden on both patients and health-care systems, and understanding wound healing principles is crucial across medical and surgical specialties to help mitigate such complications. One of these longstanding principles, specifically delayed primary closure (DPC), described as mechanically closing a wound after several days of secondary intention healing, lacks clear consensus on its definition, indications, and outcomes. This practical review examines wound healing fundamentals, focusing on DPC, its execution, indications, and comparative outcomes. A PubMed literature search was conducted to retrieve studies on DPC. Inclusion criteria included comparative studies assessing outcomes and complications between DPC and other closure techniques, as well as articles investigating DPC’s underlying physiology. Twenty-three comparative studies met inclusion criteria. DPC wounds have significantly higher partial pressure of oxygen, higher blood flow, and higher rates of collagen synthesis and remodeling activity, all of which help explain DPC wounds’ superior mechanical strength. DPC seems most beneficial in contaminated wounds, such as complicated appendectomies, postcardiac surgery wounds, and complicated abdominal wall reconstructions, where it has been associated with lower rates of surgical site infections. This practical review provides an evidence-based approach to DPC, its physiology, technique, and indications. Based on the existing literature, the authors recommend that DPC wounds should be dressed in saline/betadine soaks, changed and irrigated daily, with delayed closure lasting between 3 and 5 days or until the infection has resolved. The clearest indications for DPC are in the context of contaminated abdominal surgery and sternal wound dehiscence post cardiac surgery.
LANCL1, a cell surface protein, promotes liver tumor initiation through FAM49B-Rac1 axis to suppress oxidative stress
Authors: Huang Hongyang , Tsui Yu-Man , Ho Daniel Wai-Hung , Chung Clive Yik-Sham , Sze Karen Man-Fong , Lee Eva , Cheung Gary Cheuk-Hang , Zhang Vanilla Xin , Wang Xia , Lyu Xueying , Ng Irene Oi-Lin
Published: August 2023

Background and Aims:

HCC is an aggressive cancer with a poor clinical outcome. Understanding the mechanisms that drive tumor initiation is important for improving treatment strategy. This study aimed to identify functional cell membrane proteins that promote HCC tumor initiation.

Approach and Results:

Tailor-made siRNA library screening was performed for all membrane protein-encoding genes that are upregulated in human HCC (n = 134), with sphere formation as a surrogate readout for tumor initiation. Upon confirmation of membranous localization by immunofluorescence and tumor initiation ability by limiting dilution assay in vivo, LanC-like protein-1 (LANCL1) was selected for further characterization. LANCL1 suppressed intracellular reactive oxygen species (ROS) and promoted tumorigenicity both in vitro and in vivo. Mechanistically, with mass spectrometry, FAM49B was identified as a downstream binding partner of LANCL1. LANCL1 stabilized FAM49B by blocking the interaction of FAM49B with the specific E3 ubiquitin ligase TRIM21, thus protecting FAM49B from ubiquitin-proteasome degradation. The LANCL1-FAM49B axis suppressed the Rac1-NADPH oxidase-driven ROS production, but this suppression of ROS was independent of the glutathione transferase function of LANCL1. Clinically, HCCs with high co-expression of LANCL1 and FAM49B were associated with more advanced tumor stage, poorer overall survival, and disease-free survival. In addition, anti-LANCL1 antibodies targeting the extracellular N-terminal domain were able to suppress the self-renewal ability, as demonstrated by the sphere formation ability of HCC cells.

Conclusions:

Our data showed that LANCL1 is a cell surface protein and a key contributor to HCC initiation. Targeting the LANCL1-FAM49B-Rac1-NADPH oxidase-ROS signaling axis may be a promising therapeutic strategy for HCC.
Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma
Authors: Li Binghua , Li Yunzheng , Zhou Huajun , Xu Yanchao , Cao Yajuan , Cheng Chunxiao , Peng Jin , Li Huan , Zhang Laizhu , Su Ke , Xu Zhu , Hu Yue , Lu Jiaming , Lu Yijun , Qian Liyuan , Wang Ye , Zhang Yuchen , Liu Qi , Xie Yuanyuan , Guo Sheng , Mehal Wajahat Z. , Yu Decai
Published: August 2023

Background and Aims:

Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy.

Approach and Results:

We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies.

Conclusions:

We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making.
Comparisons of Clinical Competency and Job Responsibilities of Physical Therapists With and Without Postprofessional Training
Authors: Briggs Matthew S. , Gulla Nicholas , Howald Heidi , Weber Mark D. , Olson-Kellogg Becky J. , DeWitt John J. , Hensley Craig P. , Harrington Kendra L. , Kidder Melissa S. , Farrell Joseph P. , Tichenor Carol Jo
Published: August 2023

Introduction.

Understanding how educational pathways may influence clinical competence and work responsibilities is important in providing guidance to academic and clinic stakeholders and physical therapists (PTs) on PT career development. The purpose of this paper was to compare perceived clinical competency and job duties between PTs with formal mentored postprofessional clinical education with PTs without formal postprofessional clinical education.

Review of Literature.

The understanding of self-perceived clinical competence of PTs overall in the United States is limited, especially as related to the impact of postprofessional education. Furthermore, there is limited understanding of the career pathways and development of job duties of PTs in the United States.

Subjects.

Two thousand three hundred thirty-four PTs in the United States.

Methods.

An online survey was sent to licensed PTs. This survey included items measuring self-perceived clinical competency and questions related to weekly job responsibilities. Participants were categorized as residency trained, fellowship trained, or non–residency/fellowship trained. Frequency analyses and Kruskal–Wallis tests with pairwise post hoc tests were performed comparing the 3 groups.

Results.

Residency-trained (P < .007) and fellowship-trained (P < .001) groups demonstrated elements of higher self-perceived clinical competency compared with the non–residency-/fellowship-trained group. Both the residency- and fellowship-trained groups spent less time with patient care and more time with other responsibilities (e.g., teaching, mentoring, and research) (P < .02) during an average workweek. Fellowship-trained PTs (P < .001) spent more time with administrative duties compared with the non–residency-/fellowship-trained group.

Discussion and Conclusion.

Results from this paper demonstrate that residency- and fellowship-trained PTs have elements of higher self-perceived clinical competency and spend more of their job duties outside of direct patient care compared with PTs who were not residency or fellowship trained. These results may help guide PTs, academic institutions, and employers in planning and achieving specific career paths.
Knowledge and attitude of Lebanese women about cosmetics: a cross-sectional survey
Authors: Chahine Bahia , Hanna Venise , Ghandour Inasse , Haydar Sahar , Faddoul Lama
Published: August 2023

Background:

The Middle East and North Africa region, including Lebanon, is well known for its excessive cosmetics expenditure. While the use of beauty products is increasing, it is unclear if customers are aware of the products’ safety and proper use.

Objective:

To explore Lebanese women’s knowledge and attitudes toward cosmetics use.

Methods:

A cross-sectional study was conducted from January to May 2021 among a sample of adult Lebanese women. Data were collected using an electronic questionnaire divided into 3 sections (sociodemographic characteristics, cosmetics knowledge, and attitude) and shared via social media platforms. Knowledge and attitude scores were then calculated. Descriptive and regression analysis was performed using Statistical Package for the Social Sciences.Pvalue < .05 was considered statistically significant.

Results:

A total of 1,051 females completed the survey, and the age range of the majority 744 (70.8%) was between 18 and 20 years. The mean score of participants’ knowledge was 7.54 ± 2.7 (range 0–14) with 658 (62.6%) of the respondents being knowledgeable about cosmetics. The study sample exhibited an overall positive attitude toward cosmetics. A significant association was observed between the area of residency and monthly income of respondents and their knowledge toward cosmetic products (P< .001).

Limitations:

The self-administered questionnaire may have resulted in information bias and it targeted only those having internet access, and the age group 18 to 20 years was overrepresented.

Conclusion:

The study sample demonstrated a good level of knowledge as well as a positive attitude toward cosmetics. However, raising awareness on the acute and chronic side effects of cosmetics is warranted.
Prevalence of Anti-Saccharomyces Cerevisiae Antibodies (ASCA) in Patients With Irritable Bowel Syndrome (IBS). A Case-control Study
Authors: Thomas-Dupont Pablo , Izaguirre-Hernández Irma Yadira , Roesch-Dietlen Federico , Grube-Pagola Peter , Reyes-Huerta Job , Remes-Troche José María
Published: August 2023

Background:

Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction that affects patients’ quality. Recent research has shown variations in the mycobiome of individuals with IBS, particularly involving Saccharomyces cerevisiae, and its association with dysbiosis and visceral hypersensitivity. However, the role of Anti-Saccharomyces cerevisiae antibodies (ASCA) in IBS remains unclear, despite their significance as markers of disease severity in inflammatory bowel disease.

Objective:

This study aimed to investigate the role of ASCA in Mexican IBS patients compared with healthy controls (HCs) and determine whether these antibodies could help differentiate between IBS patients and healthy individuals.

Methods:

Serum samples from 400 IBS patients and 400 HC were analyzed. ASCA IgG levels were measured using enzyme-linked immunosorbent assay (ELISA). The IBS patients were further categorized into subtypes: constipation predominant (IBS-C), diarrhea predominant (IBS-D), and mixed (IBS-M).

Results:

Among the participants, 66 IBS patients (16.5%) and 63 HC (15.75%) tested positive for ASCA IgG. No significant difference was observed in ASCA IgG levels between the 2 groups (P value: 0.8451). The prevalence of ASCA IgG positivity was 14.5% in IBS-C, 17.8% in IBS-D, and 15.9% in IBS-M.

Conclusion:

Surprisingly, a high prevalence of ASCA IgG was found in the HC group in Mexico. Furthermore, there was no significant difference in ASCA IgG levels between IBS patients and controls. These findings suggest that ASCA is not useful as a discriminatory biomarker for distinguishing IBS patients from healthy individuals and cannot serve as a surrogate marker for visceral hypersensitivity.
Efficacy and Safety of Olanzapine for the Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Meena Jagdish Prasad , Gupta Aditya Kumar , Jat Kana Ram , Anandani Garima , Sasidharan Anju , Tanwar Pranay
Published: August 2023

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant.