bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B030: Induction chemotherapy plus concurrent chemoradiotherapy led to clinical complete response in locally advanced sinonasal rhabdosarcomas
Authors: Wu Qiuji , Li Shaojie , Wang Juan , Liu Jia , Zhong Yahua 
Published: September 2022

Abstract
Background: Sinonasal rhabdosarcoma is a rare but aggressive malignancy. In cases where locally advanced diseases involve critical structures such as the orbital and cranial cavities, surgery may not guarantee safety margin. Therefore, we evaluated the effect of induction chemotherapy plus concurrent chemoradiotherapy in locally advanced sinonasal rhabdosarcoma. Methods: During January 2013 to January 2019, 4 patients (2 males and 2 females, 22 to 33 years old) with locally advanced sinonasal rhabdosarcoma (3 alveolar and 1 poorly differentiated rhabdosarcoma) were treated with induction chemotherapy followed by concurrent radiochemotherapy. The patients were staged as cT4N0M0, cT4N0M0, cT4N1M0, and cT3N1M0 respectively. The patients were treated with induction chemotherapy composed of 2 to 4 cycles of EI regimen (epirubicin 60mg/m2, day 1-day 2; Ifosfamide 1.8g/m2, day 1-day 5; every 21 days) based on their tolerance. Thereafter, all patients received concurrent radiochemotherapy with 70Gy in 30 fractions given to the primary tumors and 63Gy in 30 fractions to the lymph nodes in N1 patients. Concurrent chemotherapy with cisplatin (100mg/m2, day 1 and day 22) was delivered during the course of radiotherapy. The follow-up time was 29, 28, 7 and 4 months, respectively. Results: Induction chemotherapy yielded partial response and concurrent radiochemotherapy led to clinical complete response. No sign of local recurrence was detected until the last follow-up. Only one patient had vertebral metastasis 6 months post-treatment in T10 and received vertebral irradiation. Others were free of distant metastasis. During the induction chemotherapy, all patients were presented with grade IV leucopenia, 3 of whom developed febrile neutropenia that required dose reduction in the consecutive chemotherapies. Concurrent radiochemotherapy was well tolerated, 3 patients developed grade II leucopenia and 1 grade IV leucopenia. All patients experienced grade II gastrointestinal side effects, dermatitis, and stomatitis. Conclusions: Induction chemotherapy plus concurrent chemoradiotherapy could lead to clinical complete response in locally advanced sinonasal rhabdosarcoma. Hematological toxicities were the most common toxicities and should be monitored and treated carefully. Longer follow-up and larger scale of study are needed to confirm these results.
Citation Format: Qiuji Wu, Shaojie Li, Juan Wang, Jia Liu, Yahua Zhong. Induction chemotherapy plus concurrent chemoradiotherapy led to clinical complete response in locally advanced sinonasal rhabdosarcomas [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B030.
Abstract IA010: Novel targeted therapy approaches in NF1-MPNST
Authors: Pratilas Christine A. 
Published: September 2022

Abstract
NF1 is an essential negative regulator of RAS activity and its function is lost in nearly 90% of malignant peripheral nerve sheath tumors (MPNST). Additional recurrent molecular changes include loss of function alterations in CDKN2A, TP53, EED and SUZ12, but molecular targeting of these genomic events represents a unique challenge. We previously reported that the efficacy of MEK inhibitor is limited by adaptive activation of receptor tyrosine kinases and the adaptor protein SHP2, and that combined inhibition of MEK and SHP2 is effective in MPNST. However, the clinical potential of combination MEK and SHP2 inhibitors may be limited by the overlapping toxicity induced by ERK pathway inhibition. Genetic depletion of PTPN11 has substantial growth inhibitory effects in preclinical models of MPNST, suggesting that SHP2 is an exciting new focus for targeted therapy development in NF1-MPSNT. Loss of CDKN2A, inactivation of RB1, and hyperactivation of cyclin dependent kinases (CDK) in MPNST also suggest that small-molecule CDK4/6 inhibitors (CDK4/6i) may offer a potential combination strategy. Our preclinical data suggest that this combination is active, well-tolerated, and has the potential for immediate advancement into clinical trials.
Citation Format: Christine A. Pratilas. Novel targeted therapy approaches in NF1-MPNST [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA010.
Abstract IA026: Epigenetic and genomic features define distinct cellular states with possible therapeutic relevance in osteosarcoma
Authors: Sweet-Cordero E. Alejandro 
Published: September 2022

Abstract
The Osteosarcoma (OS) genome is characterized by aneuploidy and dramatic structural rearrangements often leading to copy number gain and loss. Currently, all patients with osteoblastic OS at diagnosis are treated with the same highly toxic chemotherapy and no clinically relevant subtypes have been identified. While there is significant heterogeneity at the genome level between patients, less is known regarding epigenetic heterogeneity and how this may impact critical phenotypes such as therapy response and metastasis. To characterize the osteosarcoma epigenome, we integrated ATAC-seq and RNA-seq across a unique set of patient samples, PDXs and PDX-derived cell lines obtained across the disease continuum and including biopsies, resections, and metastasis. ATACseq analysis revealed the presence of two distinct epigenetic cell states (C1 and C2). Associating the differential genomic regions to likely regulated genes, the enriched pathways of Cluster 1 (C1) are related to mesenchymal cell proliferation, skeletal system morphogenesis, osteoblast differentiation, and Wnt signaling pathway. In contrast, Cluster 2 (C2) enriched pathways are related to cell motility and migration, extracellular matrix organization and regulation of protein serine/threonine kinase activity. Furthermore, accessible chromatin regions were enriched for a distinct set of transcription factor binding sites. We then assessed whether these epigenetic states were associated with response to targeted therapies. We identified unique vulnerability of C1 cell lines to AURK inhibitors whereas C2 cell lines had evidence for upregulation of MAPK and were vulnerable to treatment with trametinib. ATACseq analysis of PDX and a limited number of patient samples confirmed that these subtypes of OS also likely exist in patient tumors. In parallel to these studies, we have also carried out extensive additional analysis of vulnerability of OS cell ines to a wide range of targeted therapies. We find evidence for significant response to several inhibitors of the ATR-WEE1-CHK1 pathway nominating this as a potential novel vulnerability for OS. Therapeutic relevance of these findings is currently being explores in an orthotopic metastasis model of OS. Overall, our findings may define new subtypes of osteosarcoma with unique therapeutic vulnerabilities.
Citation Format: E. Alejandro Sweet-Cordero. Epigenetic and genomic features define distinct cellular states with possible therapeutic relevance in osteosarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA026.
Abstract PR008: The 3D epigenome of rhabdomyosarcoma
Authors: Gryder Berkley E. , Osman Issra , Durbin Adam , Qi Jun 
Published: September 2022

Abstract
Rhabdomyosarcoma (RMS) is driven by transcription factors that set up super-enhancers: large clusters of transcriptional machinery accumulated at oncogenes. Super-enhancers are also the key vulnerability of RMS, as we have revealed by CRISPR screening and chemical genomics. However, the identification of super-enhancers is inconsistent, because they are extracted from 1-dimensional ChIP-seq data, but are in fact 3D genomic objects (“super-clusters”) that form biomolecular condensates (phase-separated droplets). We have now applied new 3D genomics approaches to enable proper discovery of these epigenomic features, also yielding proper enhancer-gene connectivity maps. Furthermore, super-clusters are co-built by transcription factors recruiting p300 (acetylation writer) and BRD4 (acetylation reader). We have generated preliminary evidence that directly perturbing/degrading p300 and BRD4 are the most effective and selective means to shut down super-clusters at all oncogenes driving this childhood cancer. We applied Absolute Quantification of Architecture (AQuA) HiChIP, and were able to uncover the drug-induced 3D folding abnormalities that selectively halt RNA-Polymerase 2 at super-cluster driven oncogenes in this sarcoma.
Citation Format: Berkley E. Gryder, Issra Osman, Adam Durbin, Jun Qi. The 3D epigenome of rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr PR008.
Digital real-time microscopy of ex-vivo tissues: A novel strategy to control surgical accuracy
Authors: Sighinolfi Maria Chiara , Cimadamore Alessia , Cassani Alessandra , Assumma Simone , Sarchi Luca , Filippi Beatrice , Turri Filippo , Reggiani Bonetti Luca , Maiorana Antonino , Eissa Ahmed , Micali Salvatore , Montironi Rodolfo , Rocco Bernardo 
Published: September 2022

Introduction: Ex-vivo FCM is a novel digital optical technique that provides images of fresh tissues in a real-time fashion with magnification to subcellular details of a flattened unprocessed sample. Digital images are hematoxylin-eosin-like and can be shared and interpreted remotely. In urology, FCM has been successfully applied for prostate tissue interpretation, either during biopsy and radical prostatectomy. Possible applications of FCM may reflect those of frozen section analysis and can be extended to all fields in which the intra-operative microscopical control is advisable. Materials and methods: This is an investigative prospective case series that aims to explore FCM feasibility in novel surgical settings and provide a depiction of FCM digital images in those fields. The definite purpose is to check the accuracy of surgical specimen during the following interventions: (a) trans-urethral resection of bladder tumors, to confirm the presence of muscular layer; (b) biopsy of a retroperitoneal mass, to check for the location and quality of cores; (c) training in robotic radical prostatectomy, to control surgical margins after a nerve sparing performed by a trainee. To this aim, we collected FCM images during seven surgical procedures. FCM findings were compared to those from the final histopathological analysis and the agreement was assessed. Results: In all cases, FCM digital images were obtained in the OR. FCM was able to confirm the presence of muscular layer in TURB specimen, the presence of lymphomatous tissue, surgical margins at prostate specimen. FCM intra-operative interpretation was consistent with final histopathology in all cases. Conclusions: Ex vivo FCM may represent a novel approach to control the quality of specimens, likely to tailor surgical strategy in a real-time fashion. Moreover, digitalization represents a step toward the implementation of telepathology in clinical practice.
Three-Dimensional Quantification of Postoperative Facial Asymmetry in Patients With Unilateral Cleft lip and Palate Using Facial Symmetry Plane
Authors: Shiigi Ayano , Okawachi Takako , Kamiya Tohru , Hosoki Daisuke , Nomoto Namiko , Ratman Mohamad Farid , Amir Muhammad Subhan , Ishihata Kiyohide , Nakamura Norifumi 
Published: September 2022

Objective To quantitatively assess three-dimensional (3D) soft tissue facial asymmetry in patients with unilateral cleft lip and palate (UCLP) who have undergone primary lip repair. Design Clinical, retrospective, comparative, methodological study. Patients/Participants Twenty patients with UCLP were selected after a review of the records. Inclusion Criteria Complete UCLP; surgically treated without secondary repair. An age-matched and sex-matched Control group was employed. Main Outcome Measures A 3D facial symmetry plane (FSP) was obtained by superimposing the point clouds of the original 3D facial image excluding the surgical site and including lip and nose areas and those of a mirrored facial image using the iterative closest point (ICP) adjustment method. The discrepancies in the depth and angle of the normal vector of the facial surface of each point cloud between right and left sides (cleft and non-cleft sides in the UCLP group, respectively) based on FSP were calculated. Results Facial asymmetry in the UCLP group was significantly greater than in the Control group regarding both the discrepancies in the depth (1.34 ± 0.62, 0.73 ± 0.32 pixels, respectively) ( P = .0004) and surface angle (18.0 ± 5.88, 12.8 ± 4.0°, respectively) ( P = .0024). Biaxial assessment of the discrepancies in the depth and surface angle allowed us to visually extract UCLP patients with greater facial asymmetry. Conclusions Facial asymmetry analysis based on 3D FSP effectively facilitates the facial asymmetry quantification and soft tissue surgical outcome evaluation in patients with UCLP.
Determinants of Cervical Cancer Screening Service Utilization Among HIV-Positive Women Aged 25 Years and Above Attending Adult ART Clinics in Southern Tigray, Ethiopia
Authors: Gebrekirstos Lielt Gebreselassie , Gebremedhin Meron Hadis , Tafesse Tiwabwork Tekalign , Tura Tilahun Saol , Geleso Mulugeta Geremew , Wube Tsiyon Birhanu 
Published: September 2022

Background Cervical cancer and human immunodeficiency virus prevention are public health priorities in Ethiopia. Despite cervical cancer being preventable with the Human Papilloma Virus vaccine and cervical cancer screening, HIV-infected women still have a low rate of screening, and data are scarce in this country. Thus, this study aimed to assess the prevalence of cervical cancer screening service utilization and associated factors among HIV-positive women in Southern Tigray, Ethiopia, 2018. Methods A facility-based cross-sectional study was performed from March 1st to May 15th, 2018. We recruited 465 HIV-positive women using a systematic random sampling method. Data were collected using a pre-tested structured interviewer-administered questionnaire. Descriptive statistics, followed by multivariable logistic regression analysis were performed. Crude odds ratios, adjusted odds ratios, and 95% confidence intervals (CIs) were reported. Results In this study, only 8% of HIV-positive women were screened for cervical cancer. The most frequently cited barrier by participants to getting screened was feeling healthy 282 (65.9%). Multiparity {AOR = 4.12, 95% CI = (1.70, 9.95)}, provider recommendation to get screened {AOR = 3.20, 95%CI = (1.34, 7.65)}, having good knowledge {AOR = 4.33, 95%CI = (1.66-11.29)}, and high perceived susceptibility for cervical cancer {AOR = 3.10, 95% CI = (1.31-7.33)} were the factors significantly associated with cervical cancer screening service utilization. Conclusions The prevalence of cervical cancer screening service utilization was quite low. Provider’s recommendation to get screened, multiparity, knowledge, and perceived susceptibility were factors strongly associated with the service utilization. There is a need of routine counseling of health care providers for all HIV-positive women to get screened. Women’s lack of knowledge also needs to be addressed by informing every HIV-positive woman that they are more susceptible to cervical cancer, and that screening is critical to fighting against the disease.
Clinical outcomes at medium-term follow-up of COVID-19
Authors: Barbara Jessica-Marie , Gatt Jessica , Xuereb Rachel-Anne , Tabone Adami Nicholas , Darmanin Jessica , Erasmi Renee , G Xuereb Robert , Barbara Christopher , Stephen Fava , Jane Magri Caroline 
Published: September 2022

Background: The long coronavirus disease 2019 (COVID-19) syndrome is defined as persistent physical, cognitive and/or psychological symptoms that continue for more than 12 weeks following the acute illness. Methods: In all, 2,646 patients were randomly selected from all individuals who were diagnosed with COVID-19. They were interviewed so as to assess the persistence of symptoms and health-related quality of life. Blood investigations were also taken. Results: The median (interquartile range (IQR)) age was 44 (31–55) years and 48.6% were males. Five per cent had been hospitalised. Follow-up was for a median of 142 days (IQR: 128–161). Twenty-two per cent of the participants claimed that they were feeling worse than they felt before COVID-19. The most common symptoms were anosmia, ageusia, fatigue, shortness of breath, headaches and myalgia. The Short Form-36 questionnaire revealed that 16.4% felt that they were somewhat worse than in the previous year and that hospitalised patients fared worse in all domains except for role-emotional. New-onset diabetes was similar to the rate of undiagnosed diabetes in the background population. Hospitalised patients had significantly higher liver transaminases, fasting plasma glucose, glycated haemoglobin, uric acid, red cell distribution width, mean platelet volume, triglyceride levels and troponin levels but lower estimated glomerular filtration rate and high-density lipoprotein-cholesterol at follow-up. Discussion: A significant proportion of patients were symptomatic at a median follow-up of 142 days and felt worse than 1 year previously. Hospitalised patients had more biochemical and haematological abnormalities compared to non-hospitalised ones, suggesting ongoing inflammation in subjects who were more severely affected by the disease.
“Staying at Home”: A pivotal trial of telemedicine-based internal medicine hospitalization at a nursing home
Authors: Barkai G , Amir H , Dulberg O. , Itelman E , Gez G , Carmon T , Merhav L , Zigler S , Atamne A , Pinhasov O , Zimlichman E , Segal G 
Published: September 2022

Background In-hospital stay of acutely ill elderlies could be reduced by increasing the availability of community-based hospitalizations. The feasibility of remotely managing these patients by specialized internists, without leaving their nursing homes should be sought. In the current pivotal study, we aimed to evaluate the aforementioned model. Methods This was a prospective, open-label study at a tertiary medical center and a nursing home. The study aimed at comparing clinical outcomes of patients hospitalized in each location. Results Over a period of 5.5 months, we recruited 18 patients designated for hospitalization, meeting our inclusion criteria to either in-hospital stay or staying in their nursing home and treated by means of telemedicine from our tertiary medical center. The mean age was 85.3 years. Out of 114 hospitalization days, 44 days (48%) were at the nursing home. No significant difference was noted in terms of age, gender, and length of stay between the patients who were hospitalized in either location. In almost all cases, diagnosis changed during hospitalization. Three patients died during the study, all included in the in-hospital group. No safety breaching events happened in the nursing home-hospitalization group. Conclusions Remote, telemedicine-based hospitalization of nursing home-dwelling elderlies is safe and feasible, potentially reducing the length of in-hospital stay by almost 50%. Larger studies in this realm are warranted.
The association of Serratus Anterior Plane blocks with postoperative opioid use and analgesia following simple lumpectomy: a retrospective cohort analysis
Authors: Alexander Brenton , Mehdipour Soraya , Lee Seung Woo , Said Engy T. , Gabriel Rodney A. 
Published: September 2022

Abstract
Background
The potential benefit of regional interventions for simple lumpectomy breast cancer surgeries has not been well investigated. Understanding which patients to not offer a regional intervention to can be just as important as knowing which would benefit. It is unclear whether fascial plane blocks, such as serratus anterior plane (SAP) block, should be routinely performed for less extensive breast surgeries. Therefore, our goal in this retrospective cohort study was to evaluate the association of integrating SAP blocks into a standard perioperative multimodal analgesia plan in patients undergoing simple lumpectomies (without node biopsies) with perioperative opioid consumption. As secondary outcomes, we also analyzed postoperative pain scores and post-anesthesia care unit (PACU) length of stay.

Methods
This was a single institution retrospective cohort study (surgical site infiltration only versus SAP block cohorts) assessing the association of SAP blocks to our outcomes of interest. In the adjusted analysis, we created matched cohorts using 1:1 (surgical site infiltration only: SAP block) propensity-score matching using nearest neighbor-matching without replacement. To compare the primary and secondary outcomes in the matched cohorts, we used the Wilcoxon signed rank test. A P-value of < 0.05 was considered statistically significant.

Results
There were 419 patients included in the analysis, in which 116 (27.7%) received a SAP block preoperatively in addition to our standard perioperative analgesia plan. In an unadjusted analysis, no differences were seen in perioperative opioid consumption, PACU pain scores, and PACU length of stay. Among the matched cohorts, the median [quartile] perioperative opioid consumption in the surgical site infiltration only versus SAP block cohorts were 10 mg [10, 13.25 mg] and 10 mg [7, 15 mg], respectively (P = 0.16). No differences were seen in the other outcomes.

Conclusions
In this study, we evaluated the impact of SAP blocks on patients undergoing simple lumpectomies, which are relatively less involved breast surgeries. We concluded that routine use of preoperative regional anesthesia is not beneficial for these specific patients. Future studies should focus on identifying patients that would directly benefit from regional interventions.
Does altitude increase the risk of traumatic aortic injuries? A retrospective cohort study among six level I trauma centers in the United States
Authors: Jarvis Stephanie , Rudersdorf Patrick , Poling James , Hennig Andreas , Salottolo Kristin , Bouchard Travis , Tanner Allen , Erickson Wendy , Bhuller Sidra , Ouderkirk Logan , Simpson Jeffrey , Banton Kaysie , Kim Elizabeth , Bar-Or David 
Published: September 2022

Abstract
Background
Traumatic aortic injuries (TAIs) are rare but are associated with a high mortality. Prior studies have shown skiers and pilots, whose injuries occur at high altitudes, are at an increased risk for a TAI. The purpose of this study was to examine the effect of altitude on the incidence of TAIs across all causes of injury.

Methods
This retrospective cohort study at six Level I trauma centers (8/1/2016–1/1/2020) included adult blunt trauma patients with a chest or abdomen injury. High altitude injuries (> 5000 ft.) were compared to low altitude injuries (≤ 5000 ft.). The primary outcome was incidence of TAI.

Results
There were 8562 patients, 37% were at high altitude and 63% at low altitude. High altitude patients were older (p < 0.01), more often Caucasian (p < 0.01) and had a higher ISS (p < 0.01). There was a significantly greater incidence of TAI at high altitude than low altitude (1.5% vs. 1.1%, p = 0.01). The median altitude was significantly higher for patients with a TAI than for patients without a TAI (5100 ft. vs. 1400 ft., p = 0.01). After adjustment, high altitude patients had 2-fold [OR: 2.4 (1.6, 3.7)] greater odds of having a TAI than low altitude patients.

Conclusion
TAIs were more prevalent among high altitude injuries. Providers should be aware of the increased incidence of TAIs at high altitudes particularly when there is a delay in diagnosis and transfer to a trauma center with appropriate resources to manage these critical injuries. TAI screening at high altitude trauma centers may improve survival rates.