bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional assessment for 891 patients with common cancer in a cancer hospital of southwest China.
Authors: Yu Huiqing , Chen Mengting , Zhang Junhui
Published: June 2024

e23280

Background: Malnutrition is a problem affecting tumor patients greatly. To investigate the nutritional status of hospitalized patients with common malignant tumor in a cancer hospital of Southwest China. Methods: From April 2017 to May 2021, we enrolled 891 patients with cancer hospitalized for treatment in Chongqing university Cancer Hospital. These patients were diagnosed with one of the following 16 different types of malignant tumors: lung cancer, gastric cancer, liver cancer, colorectal cancer, breast cancer, esophageal cancer, cervical cancer, endometrial cancer, nasopharyngeal carcinoma, malignant lymphoma, leukemia, pancreatic cancer, ovarian cancer, prostate cancer, bladder cancer and brain tumor. Patient-generated subjective global assessment (PG-SGA), anthropometric measurements, and laboratory examination were used to evaluate the nutritional risk or nutritional status.Cancer pain status were assessed with the Numerical Rating Scale (NRS). We also investigated the nutritional therapy of these cancer patients. Results: According to the PG-SGA score, 48.7% (434/891) of the cancer patients were severe malnutrition (PG-SGA≥9), 31.2% (312/891) were moderate malnutrition (8≥PG-SGA≥4), 14.7% (131/891) were mild malnutrition (PG-SGA 2~3), and only 5.4% (48/891) patients were no malnutrition (PG-SGA 0~1) . The rate of malnutrition for gastrointestinal cancer patients is higher than Nongastrointestinal cancer patients (67.3% vs. 44.6%, χ2 = 31.48, P < 0.001). Multiple linear regression analysis, PG-SGA scores and body mass index (P < 0.001), serum total protein(P < 0.001), hemoglobin serum(P < 0.001), albumin (P < 0.001), prealbumin ( P< 0.001), calf circumference (left side, P = 0.001) were correlated. Age(≥65 years), albumin( < 40g/L), prealbumin ( < 150mg/L) and cancer pain (NRS≥4) are the risk factors of severe malnutrition. However, only 26.8% (200/746) of all the moderately and severely malnourished patients received nutritional therapy. Conclusions: 94.6% of the common malignant tumor patients enrolled in the present study were malnutrition. PG-SGA is an effective tool to assess malnutrition in cancer patients, it is recommended to conduct routine assessment of cancer patients at the beginning of admission. Nutritional therapy of malignant tumor patients with malnutrition is very low. Suggestions for patients with malignant tumor after admission nutritional risk screening, and comprehensive nutritional evaluation, including PG-SGA score, and to give the right nutritional therapy.
Real-world data of cancer-associated venous thromboembolism in a tertiary-care hospital in India.
Authors: Mahapatra Manoranjan , Upadhaya Prashun , Aggarwal Mukul , Dass Jasmita , PUSHPAM DEEPAM , Dhawan Rishi , Kumar Pradeep , Viswanathan Ganesh Kumar , Seth Tulika
Published: June 2024

e23298

Background: Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with various malignancies. Anticoagulation is crucial for preventing and treating thrombosis associated with cancer. However, its use faces challenges due to increased risks of bleeding, recurrent thrombosis and complexities in dosing, particularly in patients with concurrent comorbidities. Prophylactic anticoagulation is under-utilized and the cost of low- molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. Methods: It was an ambispective observational study. All the cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in north India between 2018 and 2023 were analysed. Patient demographics, disease-related and treatment-related parameters were collected and analysed. The study was approved by the Institute Ethics Committee. Results: A total of 1312 patients attended the thrombosis clinic during study period, of which 139 (10.59%) cases were Cancer-associated VTE. The median age was 48 years and 61.2% were female. Most of VTE (54.6%) occurred within 6 months of cancer diagnosis and only 7% occurred after 3 years. Gynaecological malignancies (25.18%) and adenocarcinomas (21.58%) were the most common site and histological type of cancer respectively. Common risk factors observed for VTE development were: active cancer (80.3%), active chemotherapy (36.7%), cancer surgery (15.1%). Lower limb thrombosis was the most commonly seen type (46%), while abdominal and pulmonary thrombosis were seen in 17% and 7.9% respectively. Out of total patients, 124 (89.2%) patients received anticoagulation. Low molecular weight heparin (LMWH) was used as an initial anticoagulation in majority (52.41%) and direct oral anticoagulant (DOACs) was used as long term anticoagulation in 54% of patients. In 26 patients, anticoagulation was interrupted, the major reasons being bleeding and thrombocytopenia. There was no significant difference in frequency of bleeding with use of different anticoagulants (P = 0.48). Conclusions: Most cases of cancer associated VTE occur shortly after cancer diagnosis. Prophylactic anticoagulation is still underutilized in our patients with cancer. Early suspicion and prompt treatment can improve quality of life in such patients.
Real-world outcomes and molecular correlates of incorporating immunotherapy (IO) and bevacizumab (Bev) in treating patients with peritoneal mesothelioma (PeM): A comparative analysis with pleural mesothelioma (PM).
Authors: Huey Ryan W. , Gandhi Nishant , Helmink Beth A. , Overman Michael J. , Malpica Anais , Estrella Jeannelyn , Taggart Melissa , Allam Joelle , Scally Christopher , Mansfield Paul F. , Matamoros Aurelio , Elliott Andrew , VanderWalde Ari , Ma Patrick C. , Halmos Balazs , Liu Stephen V , Fournier Keith F. , Raghav Kanwal Pratap Singh
Published: June 2024

e23300

Background: Nivolumab/Ipilimumab (IO) and Bev/Chemo are now considered standards of care for patients (pts) with advanced PM, based on randomized (CheckMate743 and MAPS) trials. By extrapolation, they are also endorsed by guidelines and used clinically in pts with PeM. Due to lack of any prospective data, we evaluated real-world effectiveness of these agents in PeM (vs PM) and investigated molecular correlates underlying their therapeutic impact. Methods: The study cohort was composed of mesothelioma pts (N = 723) who underwent DNA (592-gene panel or whole exome)/RNA (whole transcriptome) [PeM (221/224) and PM (493/499)] sequencing at Caris Life Sciences (Phoenix, AZ). Treatment and real-world survival (OS) were obtained from insurance claims and calculated from time of tissue collection to last contact. Hazard ratio (HR) was calculated using Cox proportional hazards model. Tumor microenvironment (TME) estimates were calculated from bulk RNA sequencing using QuanTIseq method. Significance was determined using Chi-square, Mann Whitney U and log-rank tests and corrected for multiple comparisons (q-value < 0.05) when applicable. Results: PeM (vs PM) had a higher proportion of females (46% vs 29%) and younger age (62 vs 73 years; both p < 0.001). 20% and 22% of PeM were treated with IO or Bev/Chemo, with similar utilization rates in PM of 22% and 24%, respectively. OS estimates and comparisons are shown in Table. Prevalence of mutations in key mesothelioma associated genes ( BAP1, NF2, TP53 and SETD2) was not significantly different between PeM and PM. NF2 (10.1 vs 51.3 m for wild type; p < 0.001) and TP53 (10.4 vs 46.6 m for wild type; p < 0.006) mutations were associated with worse OS in PeM but not in PM. Prevalence of high tumor mutation burden (≥10 mut/Mb: 1.0% vs 3.4%; q = 0.37) and PD-L1+ (18.7% vs 28.8%; q = 0.07) tumors was slightly lower in PeM than PM. Macrophage fractions, M2 were higher (1.5-fold) and M1 were lower (0.8-fold) in PeM (both q < 0.05) compared to PM. Conclusions: In this large real-world analysis, use of IO appears to be associated with improved outcomes in PeM, despite a potentially immunosuppressive TME. Notably, addition of Bev did not appear to improve outcomes in PeM, in contrast to PM. These results highlight variances in clinical utility/value of these therapies. Molecular mechanisms underlying these outcome differences warrant further investigation. [Table: see text]
Trastuzumab biosimilars interchangeability: Preliminary real-world data in neoadjuvant breast cancer setting.
Authors: Nunes Joao Soares , Prestes Ana Paula , Carneiro Marcela Bechara , Marra Ana Claudia Machado , Marquezini Isabela Rovel
Published: June 2024

e23305

Background: Interchangeability (IC) among biosimilar compounds is still an issue not completely addressed, due to concerns on adverse events, immunogenicity, and efficacy. Many regulatory agencies around the world have adopted IC aside of appropriate clinical trials evaluation. Brazil’s Public Health System (SUS) has centrally provided trastuzumab (T) for breast cancer (BC) and firstly adopted biosimilars in 2020, after their regulatory approval 2 years before. After T biossimilar adoption there was an improvement of access for its all clinical indications, however different compounds had been offered to patients (pts) along their treatment. The aim of this study is evaluating the impact of these exchanges of types of T on patient-based registry. Methods: We reviewed all pharma and clinical data between 2020 and 2022 from all pts, stage III, Her2-Positive, who received neoadjuvant treatment based on chemotherapy plus trastuzumab in a Comprehensive Cancer Center in Southern Brazil. The main objective is measuring the rates of changes among T biosimilar compounds, and its impact in pathological response (pCR), toxicity and treatment-failure rates. Chi-square, Fisher’s Exact, t-test, or Mann-Whitney testing, as appropriate, was used to compare events between groups. Results: Along the studied period, SUS had offered 3 T biosimilars: ABP 980 (Amgen), CT-P6 (Celltrion), SB3 (Samsung), plus reference trastuzumab (Roche). The standard regimen was ACq21 4cycles followed by Taxane (Docetaxel q21 or weekly Paclitaxel) plus T 4cycles. 146 pts were eligible to analysis. 83 pts received only one type of T compound (non-interchangeability group – NICG), 63 pts received at least 2 different T compounds along the treatment (Interchangeability Group – ICG). Both groups were comparable in terms of clinical features (age, ER/PR status, menopausal status, PS, tumor size, and staging of axillary lymph nodes). Rate of IC along the time was 11%, 53% and 33% in 2020, 2021 and 2022, respectively. pCR was 32,5% in NICG versus 33,3% in ICG (p:NS). In total, 3pts had their treatments interrupted due to toxicity (1pt cardiac, 2pts hematologic). Conclusions: Although IC among biosimilars compound had been globally accepted, it was not clinically fully tested. Brazilian Ministry of Health, as the only provider, has a policy based on lowest cost for trastuzumab compound, causing constant changes along pts treatments. Furthermore, it is expected that Brazil has the potential to evaluate the IC in thousands of pts prospectively next years. Hereby, we could demonstrate preliminary based on retrospective data that exchange among different biosimilar compounds did not interfere significantly on pCR, nor raised any new safety or clinical concerns.
Nationwide real-world usage of blood-based (liquid) biomarker testing in Japan.
Authors: Yatabe Yasushi , Ennishi Daisuke , Kotera Yuko , Watanabe Ryosuke
Published: June 2024

e23311

Background: Despite the advances in precision oncology with biomarker testing including CGP (comprehensive genomic profiling), not all patients are able to benefit from tissue-guided treatment decisions, underscoring a significant demand for advancements in liquid-based biomarker testing for such patients. However, the treatment landscape based on the application and integration of liquid biopsy in clinical practice has yet to be fully characterized in Japan. Methods: Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter in Japan, was established by the Ministry of Health, Labour and Welfare (MHLW) with the start of cancer genome medicine since June 2019. The database collects the clinical and genomic data from 68,242 patients who underwent CGP by the end of 2023. This study included all patient records who underwent liquid CGP testing using FoundationOne Liquid test from the C-CAT database up to June 2023. Results: We analyzed data from 7,461 records, where the patients had an average age of 65.1 (±12.0) years; 58.8% were male. A majority (51.3%) exhibited an ECOG performance status of 0, and 66.5% reported a family history of carcinoma. Predominant cancer types included pancreatic (1,825; 24.5%), prostate (1,182; 15.8%) and biliary tract cancers (838; 11.2%). Following review by an MTB (molecular tumor board), new treatments were initiated in 5.8% (434) of cases, with targeted therapy (181; 41.7%) and chemotherapy (174; 40.9%) being the primary interventions. Separately, 9 (2.1%) of new treatments post-MTB occurred as part of clinical trials. Median (IQR) durations from specimen collection to MTB, MTB to treatment initiation, and specimen collection to post-MTB treatment were 28 (24-34), 35 (13-64), and 63 (42-94) days, respectively. The largest proportion of biomarker testing occurred after the start of second line of therapy (1,720; 23.1%) Pancreatic and biliary tract cancer patients tend to have biomarker testing at the earlier line, whereas prostate and ovarian cancer patients tend to have at the later line. Conclusions: Although the positioning of liquid CGP testing may differ among cancer types, it is important for patients to select appropriate tissue- and liquid-based biomarker testing at the right timing. Understanding this descriptive landscape of biomarker tests utilized in real-world settings will aid decision-making for addressing unmet needs (e.g., low accessibility to treatment) in cancer genome medicine and its positioning in improving the standard of cancer care.
Incidence and outcomes of atrial fibrillation in different cancer subtypes: A propensity-matched analysis of Nationwide Readmissions Database.
Authors: Farooq Faryal , Kumar Manoj , Sultan Muhammad , Afzal Muhammad Sohaib , Nasir Bilal , Byreddi Laxman Yashwant , Devarkonda Vishal , Atluri Sundeep , Ali Shafaqat
Published: June 2024

e23324

Background: Significant concern exists over the cardiotoxic effects of chemo & radiation therapy used in the management of cancer patients. With different cancers requiring different chemo-radiotherapy regimens, cardiotoxicity risk is quite variable. We aim to evaluate the rates of atrial fibrillation (AF) in various cancers. Methods: The national readmission database (2016-2020) was queried to identify all-cause admissions for patients with active malignancy of any origin. The study population was divided into six subgroups based on the type of cancer (colorectal, renal, lung, breast, prostate, and hematological). Multivariate regression analysis was utilized for adjusted odds of mortality. A propensity score matching (PSM) model matched malignancy of interest with other malignancies to obtain incidence rates. Results: Among 10.6 million all-cause cancer-related hospitalizations, about 1.5 million (14%) developed atrial fibrillation (AF). On propensity-matched cohorts, AF had its highest incidence in hospitalizations associated with hematological malignancies (17%), followed by prostate (16.5%), lung (15.9%), renal (12.5%), colorectal (11.5%) & breast (10.5%) malignancies [p < 0.05]. Moreover, cancer hospitalizations complicated by AF were associated with higher mortality. AF was associated with the highest odds of mortality in breast cancer (aOR:1.60), followed by colorectal (aOR:1.59), hematological (aOR:1.55), prostrate (aOR:1.52), renal (aOR:1.51) & lung (aOR:1.51) malignancies [p < 0.001]. The rates of 30-day AF-related readmission were highest in hematological malignancies (21%), followed by lung (18.8%), colorectal (17.1%), breast (16.1%), prostate (15.7%) & renal (12.5%) malignancies [p < 0.05]. Conclusions: The rate of AF in nationwide hospitalizations among cancer patients was ~ 14%. AF was found to have the highest incidence & readmission in hematological malignancies, while AF-related mortality was highest among breast cancer.
Bony reconstruction after internal hemipelvectomy: A retrospective analysis of 44 patients undergoing femoro-pelvic pseudoarthrosis.
Authors: Mishra Biplab , Shah Mandip C. , Anchan Chetan
Published: June 2024

e23509

Background: After acetabular resection for sarcomas, achieving a bony femoro-pelvic fusion is very difficult, and prosthetic reconstructions have very high complication rates. We reconstructed the defects with a simple polypropylene mesh between the femoral head and the remaining part of the pelvis thereby aiming at a pseudo-arthrosis and analyzed its functional outcome. Methods: Between 2013 and 2022, 44 patients having bone tumors of the pelvis underwent acetabular resections and femoro-pelvic pseudoarthrosis. Commonest Histology was chondrosarcoma (23). According to Enneking’s classification, type II (3), type I+II (9) , type II+III (24), type I+II+IV (5), and type I+II+III (3) resections were carried out. A 30 x 30 cm polypropylene mesh was tied to the remains of the capsule around the head and was then turned on itself to make a strong braided rope-like structure. It was passed through the remaining ilium/ ischium/ sacrum and was tied to itself in proper rotation with heavy ethibond suture. In 4 cases, a proximal femur megaprosthesis and in 2, a nail cement spacer was implanted in femur to reduce shortening. Functional limb results were reported according to MSTS functional scores. Results: 37/44 patients attained independent ambulation. The mean time to full weight bearing was 4.7 months (3-9 months). There were 6 flap necrosis, 3 infections, 1 nerve injury, and 1 vascular injury. Local recurrence occurred in 6 (13%) and Systemic metastasis developed in 20 patients (47% of malignant tumors). At an average follow-up of 56 months ( 24 – 127 months), 26 are alive without any signs of disease. The average MSTS score was 22 (range 13–27). The best MSTS scores were with type II or II+III IH where ilium was left to support the femur while the worst was with type I+II+III resection patients. Patients with higher BMI have poorer functional outcomes with meshplasty. Conclusions: Mesh-pseudoarthrosis is a very simple reconstruction option that has an excellent functional outcome. It reduces surgical time and eliminates uncertainties about fusion/joint replacement. This should be strongly recommended as a method of reconstruction for patients undergoing acetabular resections.
Characterizing TP53 mutations in bone and soft tissue sarcoma.
Authors: Babatunde Olayode , Notti Ryan Quin , Tap William D.
Published: June 2024

e23521

Background: Tumor protein P53 (TP53) is the most frequently mutated gene in cancer and most mutations inactivate wild type TP53 activity through heterogenous mechanisms. Whether different variants of mutant TP53 have different biologic potencies or clinical outcomes remain unclear. This ongoing study aims to characterize the spectrum of TP53 mutations in patients with bone and soft tissue sarcoma. Methods: We retrospectively identified and analyzed patients with bone and soft tissue sarcoma who underwent MSK-IMPACT (Memorial Sloan Kettering Cancer Center - Integrated Mutation Profiling of Actionable Cancer Targets) next-generation sequencing panel and had at least one mutation in the TP53 gene at Memorial Sloan Kettering Cancer Center. Mutations in the TP53 gene were categorized into the following sub-types: fusion, missense, splice site, or protein-truncating. Hotspots were defined as variants with frequency of 10 or greater. We queried the missense variants for the 800 most frequent variants recorded in the International Agency for Research on Cancer R20 (IARC), which were structurally characterized based on their impact on TP53 protein and rescue potencies with arsenic trioxide (ATO) in vitro (Song et al. Sci Transl Med. 2023). Results: We identified a total of 1257 patients with bone and soft tissue sarcoma who had at least one mutation in TP53. 92.5% of patients had only 1 mutation in TP53. In total, 1363 mutations were detected with 541 variants identified across all sarcoma subtypes. Most TP53 mutations were identified in soft tissue leiomyosarcoma (18.05%), uterine leiomyosarcoma (12.84%), sarcoma not otherwise specified (15.62%), undifferentiated pleomorphic sarcoma (12.11%), and osteosarcoma (7.78%). Of the 541 variants identified, the most frequent alterations were intragenic fusion (6.23%), R175H missense (2.93%), R248Q missense (2.27%), R273H missense (2.13%), and R213* protein-truncating (2.05%) mutations. Of the 800 most frequent missense variants in IARC R20 database, 233 missense variants were detected representing 52% of all mutations detected. Structural or likely structural mutations represented most of the identified missense mutations (77.46%). These mutations were clustered in the following hotspots: R175H, Y220C, R282W, H179Y, and C135Y. DNA-contact mutations were clustered in the following hotspots: R248Q, R273H, R273C, and R248W. Conclusions: This analysis highlights the heterogenous landscape of TP53 mutations in bone and soft tissue sarcomas. Structural variants are prevalent in sarcoma and occur at hotspots that may represent novel drug targets in the future.
Differences in baseline ctDNA value between Hispanic and non-Hispanic White patients with soft tissue sarcoma (STS): A single-center retrospective analysis.
Authors: Ikram Waleed , Zamora DIana , Braat Jonathan , Dinh Han , Azevedo Chelsea , Patel Shyamal , Wiseman Jason T. , Gonzalez Velez Miguel
Published: June 2024

e23533

Background: Circulating tumor DNA (ctDNA) has shown promise as a biomarker for cancer detection and tracking in multiple malignancies like melanoma, colon and lung. Due to the heterogeneity of sarcoma, there has been limited research on ctDNA as a tool for measuring minimal residual disease (MRD). Differences in baseline in ctDNA for STS in racial minorities have been poorly studied. To identify potential racial differences in the efficacy of this tool, this study compares the quantitative values of baseline ctDNA between non-Hispanic white (NHW) and Hispanic (H) patients with soft tissue sarcoma (STS). Methods: The medical records of 33 STS patients who had ctDNA analysis from Natera™ were examined retrospectively at Dignity Health Cancer Institute.There were 19 H patients and 14 NHW patients in the group. All Black (B), Asian (A), and Other (O) racial groups were excluded due to lower numbers. GraphPad Prism software was used to examine the baseline ctDNA levels. Using continuous measures for statistical analysis, we conducted descriptive statistics and determined the mean, standard deviation, and median ctDNA levels for each group. The ctDNA levels were compared between groups using a two-tailed t-test with a significance level of p < 0.05. Results: The average ctDNA levels were 416.675 (standard deviation = 1349.394) in NHW and 300.305 (standard deviation = 1000.543) in H. The median levels were 0 for both groups. The statistical analysis showed that there was no significant differences in the baseline ctDNA levels between the two groups (p = 0.73). Furthermore, the gender distribution among NHW and Hs in the cohort was comparable, with a p-value of 1.00. Conclusions: This study establishes that there is no substantial differences in baseline levels of ctDNA between H and NHW patients with STS. These findings indicate that ctDNA levels in these populations can be equally utilized for diagnostic and monitoring reasons in clinical settings. Nevertheless, to gain a comprehensive understanding of the racial disparities in ctDNA utility and its implications in customized treatment for STS, it is necessary to conduct more extensive research with larger sample sizes and incorporate additional variables.
Peak study: A phase 3, randomized, open-label multi-center clinical study of bezuclastinib (CGT9486) and sunitinib combination versus sunitinib in patients with gastrointestinal stromal tumors (GIST).
Authors: Tap William D. , Somaiah Neeta , Kang Yoon-Koo , Abdul Razak Albiruni Ryan , Garrido Marcelo , Desar Ingrid M.E. , Italiano Antoine , Reichardt Peter , Wilky Breelyn A. , Heinrich Michael C. , Druta Mihaela , Singh Arun S. , Attia Steven , Bauer Sebastian , Serrano Cesar , Moynihan Kevin , Lawrence Julia , Wagner Andrew J. , Trent Jonathan C.
Published: June 2024

TPS11588

Background: Imatinib is the worldwide standard for first-line therapy of advanced KIT-mutant GIST. However, secondary resistance mutations in the KIT ATP-binding domain (exons 13, 14), activation loop (exons 17, 18), or both develop and result in loss of imatinib-sensitivity. Bezuclastinib has a highly selective inhibition profile, leading to minimal off-target toxicities and allowing for combination with sunitinib. While no single tyrosine kinase inhibitor (TKI) inhibits all KIT mutations, the combination of bezuclastinib + sunitinib targets commonly occurring primary (exons 9, 11) and secondary (exons 13, 14, 17, and 18) KIT mutations and may provide more durable responses. The early signs of clinical activity, tolerability, and safety observed with the combination thus far in Peak Part 1 (Somaiah et al. [presentation] CTOS 2023. Paper 62) are consistent with the completed Phase 1/2 study (PLX121-01). Methods: Peak (NCT05208047) is a global, randomized, open-label, multi-part Phase 3 study evaluating the efficacy and safety of bezuclastinib + sunitinib versus sunitinib as second-line treatment in adult pts who were intolerant to imatinib or whose tumors had imatinib-resistance. Current Peak study sites are located in North America (3 countries), South America (3 countries), Europe (12 countries), and Asia-Pacific (4 countries). The lead-in portion to test a new formulation of bezuclastinib, (Part 1) completed enrollment in April 2023. Based upon PK and safety, a dose of bezuclastinib 600 mg QD + sunitinib 37.5 mg QD was determined for Part 2 of the Peak study. Part 2 will enroll ~388 pts to be randomized (1:1) to bezuclastinib 600 mg QD + sunitinib 37.5 mg QD or sunitinib 37.5 mg QD alone. Key inclusion: >1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1, Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ function, and prior imatinib therapy (no other prior therapy). Key exclusion: known PDGFR mutations or succinate dehydrogenase deficiency, clinically significant cardiac disease, and use of strong CYP3A4 inhibitors or inducers. The primary endpoint is progression-free survival (PFS) confirmed by blinded independent central review per mRECIST v1.1. Additional efficacy (including overall survival and objective response rate) and safety endpoints will be evaluated and circulating tumor DNA (ctDNA) will be collected and assessed. Clinical trial information: NCT05208047 .
Expanding the Reach of Personalized Medicine in Cancer Care: Current Progress and Future Directions of JCO Precision Oncology
Authors: Shi Yushu , Iorgulescu J. Bryan , Valladao Stephanie , Atibalentja Danielle F.
Published: May 2024

ASCO Editorial Fellows share insights into publication trends and future directions for JCO Precision Oncology.
Awake Combined Spinal Caudal Anesthesia for Longer-Duration Urologic Surgery in Infants: A Case Series
Authors: Bean Christopher D. , Low Sarah A. , Novak Alexis B. , Chen Andrew L. , Elder Jack S. , Liu Chang A.
Published: June 2024

Awake combined spinal caudal anesthesia has been used as an anesthetic technique for longer-duration infraumbilical surgeries in infants. Literature on the safety and feasibility of this technique is limited. We share our experience with 27 infants undergoing longer-duration urologic surgery using awake combined spinal and caudal anesthesia without the use of systemic sedatives or inhalational agents. We describe our technique, safety considerations, and details surrounding the optimal timing of caudal catheter activation for prolongation of surgical anesthesia.
Unreported Source of Interference with the Bispectral Index During Liposuction: A Case Report
Authors: Katerenchuk Vasyl , Calçada Alexandre , Batista Ana Correia , Cordeiro Lisbete
Published: June 2024

Incorrect bispectral index (BIS) values have been reported due to interference with this monitoring system. We report a case of a 46-year-old woman who underwent liposuction and breast lipofilling, where we observed a misinterpretation by the BIS algorithm that has not yet been reported. Concurrently with abdominal and thigh liposuction, an increase in the BIS value was observed. The importance of examining electroencephalogram (EEG) and density spectral array (DSA) readings during liposuction procedures is highlighted in this case report, extending our observations beyond just the numerical BIS value, which is not always reliable.
Trigger Warning
Authors: Herzig Rebecca M.
Published: May 2024

Trigger warnings, statements alerting readers, listeners, or viewers to the presence of content that might revive distressing memories, have become a flash point in recent discussions about the US academy. Providing a genealogy of the concept and practice in US colleges and universities, this article situates the trigger warning's growing cultural prominence within twined changes in computer-mediated communication and legal understandings of embodied consent. Seen against this backdrop of racialized, gendered struggles over the meanings of free, voluntary action, the trigger warning debate helps illuminate how the normative regimes of the contemporary university reflect the long afterlife of US racial slavery.
Integrated analysis of -omic landscapes in breast cancer subtypes
Authors: Davitavyan Suren , Martirosyan Gevorg , Mkrtchyan Gohar , Chavushyan Andranik , Melkonyan Ani , Ghazaryan Hovsep , Binder Hans , Arakelyan Arsen
Published: June 2024

The subtypes of breast cancer exhibit diverse histology, molecular features, therapeutic response, aggressiveness, and patient outcomes. Multi-omics high-throughput technologies, which are widely used in cancer research, generated waste amounts of multimodal omic datasets calling for new approaches of integrated analyses to uncover patterns of transcriptomic, genomic, and epigenetic changes in breast cancer subtypes and connect them to disease clinical characteristics. Here, we applied multi-layer self-organizing map (ml-SOM) algorithms to PAM50-classified TCGA breast cancer samples to disentangle the diversity of the effects of gene expression, methylation, copy number, and somatic single nucleotide variation in the disease subtypes. Furthermore, we studied the association of perturbed gene modules with survival, prognosis, and other clinical characteristics. Our findings highlight the power of multi-omic analyses to offer a better understanding of the molecular diversity of breast cancer subtypes compared to single-omic analyses. Moreover, they highlight the complex subtype-characteristic associations between gene expression and epigenetic/genomic factors and their implications for survival and clinical outcomes.
Periodontitis and arrhythmias: an emerging paradigm in cardiovascular medicine
Authors: Said Aimen , Valecha Jayesh , Aggarwal Kanishk , Garg Shreya , Kanwar Rhea , Anamika FNU , Kanagala Sai Gautham , Kejriwal Swati , Jain Rohit
Published: June 2024

Periodontitis, a chronic inflammatory condition affecting the periodontal tissues and underlying bone, is now acknowledged as more than just a localized oral disease. With a global prevalence ranging from 20% to 50%, the implications of periodontitis extend beyond oral health, presenting significant concerns for public health. Research has demonstrated a strong association between periodontitis and cardiovascular disease, with shared risk factors encompassing age, smoking, socioeconomic status, and metabolic syndrome. Understanding the intricate relationship between periodontal disease and cardiovascular diseases, especially the development of arrhythmias like atrial fibrillation, is crucial. A comprehensive literature search using PubMed was conducted, employing keywords such as periodontitis, cardiovascular disease, cardiac arrhythmia, atrial fibrillation, and related terms. No exclusion criteria were used. This article reviews the current literature on the association between periodontitis and cardiovascular diseases, including atrial fibrillation. Atrial fibrillation, the most common cardiac arrhythmia, is influenced by various risk factors including alcohol consumption, advanced age, underlying heart and lung diseases, with poor oral hygiene emerging as a notable contributing factor. The direct invasion of endothelial cells by periodontal pathogens, the indirect pathway where periodontal disease triggers a systemic inflammatory response, and a shared genetic basis are three theories that explain this link. Patients with periodontal disease face an elevated risk of major cardiovascular events, especially arrhythmias, and recognizing this association is essential for healthcare practitioners to provide comprehensive care to patients with cardiac conditions.
Banana crop by-products in the Canary Islands in a biorefinery’s context
Authors: Díaz Sara , Ortega Zaida
Published: June 2024

The waste from banana food production and their use within a circular economy framework are briefly analyzed within this review. Firstly, general information on the economic value of the crop, and its relevance in the economic development of the Canary Islands are presented. Secondly, an analysis on the types of by-products that are generated in banana cultivation, both in the plantation itself (pseudostem, leaves, and flower), and in the sorting and packaging facilities (rachis and discarded bananas) is shown. The authors conclude that banana plantation residues could be recovered by applying the biorefinery concept, in line with the European guidelines on efficient use of resources.
Statistical Killing vector fields on the Hopf hypersurfaces in the complex space forms
Authors: Abedi Esmaiel , Moghanian Nasibeh , Ilmakchi Mohamad , Mosadegh Kordmahaleh Najma
Published: June 2024

Statistical Killing vector field is introduced and Hopf hypersurfaces of complex space forms with the condition of being structural statistical Killing vector field are studied. It is shown that these hypersurfaces have at most three distinct constant principal curvatures.
Condition of Renal Excretory Function in Patients with Chronic Liver Diseases
Authors: Kvasnytska O. , Gozhenko A. , Zukow W.
Published: May 2024

This study examined 37 patients with hepatitis and cirrhosis of the liver and 30 healthy individuals, assessing liver function indicators and renal function under conditions of daily diuresis and after a load of drinking water and a 0.5% sodium chloride solution, at 0.5% of body weight.
The study showed that hepatitis and cirrhosis of the liver lead to signs of hepatorenal syndrome development, particularly in patients with cirrhosis, primarily manifested by a reduction in glomerular filtration rate (GFR). The extent of reduction correlated with the severity of liver damage. Simultaneously, it was independent of blood pressure, plasma protein, and renal sodium exchange mechanisms. The primary dysfunction in hepatorenal syndrome was determined to be a reduction in GFR, evidenced by the rise in creatinine concentration, although urea increased only in cirrhosis, requiring further explanation.
The results showed that liver diseases, especially cirrhosis, can lead to kidney problems, mainly by reducing the kidney's ability to filter blood, which was shown by higher creatinine levels in the blood.
Justicia ambiental en estricto sentido
Authors: Mesa Cuadros Gregorio
Published: May 2024

Usualmente la justicia ambiental ha sido conceptualizada de manera sectorial y parcial. En este escrito, pretendemos hacerlo en estricto sentido, es decir, precisar que cobra múltiples formas con respecto a daños en la naturaleza y en la cultura (tanto a los ecosistemas como a las culturas). Una primera acepción de la justicia ambiental tiene que ver con el reconocimiento de la existencia de injusticias ambientales asociadas al uso inadecuado de la naturaleza que genera conflictos y daños ambientales, lo que afecta los derechos de terceros, al apropiarse injustificadamente de lo que es de otros, trayendo como consecuencia una distribución asimétrica e injusta de costos y beneficios ambientales. Este trabajo consta de dos partes. La primera precisa algunos momentos de la historia de la conflictividad ambiental y la segunda desarrolla los contenidos básicos de la justicia ambiental, y procura resolver las injusticias ambientales generadas por esos conflictos.
Solving the Minimum Sum Coloring Problem: Alternative Models, Exact Solvers, and Metaheuristics
Authors: Du Yu , Glover Fred , Kochenberger Gary , Hennig Rick , Wang Haibo , Hulandageri Amit
Published: May 2024

The minimum sum coloring problem (MSCP), a well-known NP-hard (nondeterministic polynomial time) problem with important practical applications, has been the subject of several papers in recent years. Because of the computational challenge posed by these problems, most solution methods employed are metaheuristics designed to find high-quality solutions with no guarantee of optimality. Exact methods (like Gurobi) and metaheuristic solvers have greatly improved in recent years, enabling high-quality and often optimal solutions to be found to a growing set of MSCPs. Alternative model forms can have a significant impact on the success of exact and heuristic methods in such settings, often providing enhanced performance compared with traditional model forms. In this paper, we introduce several alternative models for MSCP, including the quadratic unconstrained binary problem plus (QUBO-Plus) model for solving problems with constraints that are not folded into the objective function of the basic quadratic unconstrained binary problem (QUBO) model. We provide a computational study using a standard set of test problems from the literature that compares the general purpose exact solver from Gurobi with the leading QUBO metaheuristic solver NGQ and a special solver called Q-Card that belongs to the QUBO-Plus class. Our results highlight the effectiveness of the QUBO and QUBO-Plus models when solved with these metaheuristic solvers on this test bed, showing that the QUBO-Plus solver Q-Card provides the best performance for finding high-quality solutions to these important problems.

History: Accepted by Pascal Van Hentenryck, Area Editor for Computational Modeling: Methods & Analysis.

Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0334 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0334 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .
Call to put schools at the heart of mental health and wellbeing plan
Authors: Hayes Derren
Published: June 2024

Report by think-tank says next government should expand the reach and remit of mental health support teams so they provide advice and guidance to all pupils to prevent emerging problems from escalating
A Study on the Relationship Between Sayeok-tang and Systemic Inflammatory Response Syndrome
Authors: Lee Ju-Hyun , Lee Sang-Bae , Jo Eun-Heui , Park Min-Cheol
Published: June 2024

Objectives: This research is designed to analyze the relationship between Sayeok-tang(四逆湯) and systemic inflammatory response syndrome in literature.Methods: The main treatment symptoms of Sayeok-tang(四逆湯) presented in Sanghanron(傷寒論) and Geumgweyoryak (金匱要略), and the symptoms of Ju-hwang(走黃) and Nae-ham(內陷), which is a sepsis and systemic inflammatory response syndrome in Korean medicine were analyzed. The symptoms of systemic inflammatory response syndrome presented in the related researches including diagnosis criteria and international guideline presented at the consensus conference hosted by the American College of Chest Physicians and The Society of Critical Care Medicine were also compared and analyzed.Results: The main treatment symptoms of Sayeok-tang(四逆湯) and symptoms of systemic inflammatory response were very similar, and were almost identical to the symptoms of Nae-ham (內陷, especially Gun-ham (乾陷) and Heo-ham(虛陷)), which are the Korean medicine descriptions of sepsis and systemic inflammatory response syndrome.Conclusions: Based on the research results, Sayeok-tang(四逆湯) can be used as a treatment of systemic inflammatory response syndrome.
A comparative study on enhanced anti-inflammatory activity of Cannabis root extract prepared by combined processing process
Authors: Yu Ga-Ram , Jin Hye-Lin , Kim Da-Hoon , Noah Jay Kyun , Kim Hyuck , Lim Dong-Woo
Published: June 2024

Objectives: Cannabis root is a medicinal plant that has been used in traditional medicine around the world. However, in previous studies using simple extracts, the biological activity was not relatively prominent compared to other herbal medicines. The aim of the present study is to confirm the enhancement of anti-inflammatory activity and bioactive compound of Cannabis root extract prepared by combined processing process.Methods: A series of processes including repeated steam and dry, fermentation, hydrothermal extraction and ethanol extraction was applied to Cannabis root. The antioxidant content of cannabis root extracts obtained through a combined processing process was investigated by analyzing the total phenolic, tannin, and flavonoid contents. Anti-inflammatory effects were tested in LPS-treated RAW264.7 cells. The anti-inflammatory mechanism was examined by western blot. Finally, the component profile of Cannabis root extract was analyzed using High Performance Liquid Chromatography (HPLC) and Thin layer chromatography (TLC).Results: The cannabis root extract prepared by complex processing process had higher antioxidant and anti-inflammatory effects than simple extract. Total phenolic and tannin contents were significantly increased, and DPPH free radical inhibition activity was strengthened by combined processing process. Increased NO production and iNOS expression in LPS-treated RAW264.7 cells were decreased in a concentration-dependent manner upon extract treatment by complex processing process. Additionally, the Stigmasterol content of Cannabis root extract was increased through a complex processing process.Conclusions: Further research is needed on the mechanisms and substances that exhibit the anti-inflammatory effects of Cannabis roots extract prepared by complex processing process.
Prediction of Treatment Mechanisms of Scutellariae Radix on Viral Pneumonia Through Network Pharmacology: Focus on Hypoxic State Regulation Through HIF-1α and HSP90
Authors: Shon Jee-won , Han Do Kyung , Kim Youn Sook , An Won Gun
Published: June 2024

Objectives: In this study, we used network-based systems pharmacology analysis and molecular docking methods to predict the therapeutic mechanism of Scutellariae Radix on viral pneumonia.Methods: We screened active components of Scutellariae Radix and its’ genes by TCMSP. Also, we extracted viral pneumonia related target genes through Gene Cards, CTD and DisGeNet. To construct Protein-protein Interaction, STRING database was used. For functional enrichment, using SRplot platform, genes were classified by 3 categories: cellular component (CC), molecular function (MF) and biological process (BP). Molecular docking was conducted by AutoDockTools (version 4.2.6).Results: 32 Network-based systematic pharmacology analysis identified 37 target genes associated with baicalein. Based on the network and gene ontology analysis of the active ingredient's target genes and disease target genes, we identified nine core genes (AKT1, BAX, BCL2, CASP3, HIF1A, PTGS2, RELA, TP53, VEGFA) and HSP90 as involved. Notably, HIF1A showed the highest relevance, overlapping with two or more utilized programs. Hypoxia-inducible factor 1-alpha (HIF-1α) has been implicated in the expression of inflammatory cytokines, the induction of hypoxia, and the triggering of cytokine storms. Baicalein, a major component of SR, binds to both HIF-1 α and HSP90, suggesting that it may be a possible targeted treatment for viral pneumonia.Conclusions: Baicalein may bind to HIF-1α to control inflammation caused by viral infectious diseases and may also regulate hypoxic conditions to prevent impairment of lung function caused by an overactive immune system. These findings suggest further research into the molecular mechanisms involved in hypoxia and provide a scientific basis for improving the treatment of viral infectious diseases.
Development of a Standardized Clinical Pathway in Korean Patients with Gastric Cancer Clinical Application Observational Study
Authors: Lee Keon-Jun , Kim Dong Hyeon , Kim Jong-Hee , Joo Han-Eum , Cho Young-Min , Cho Jung-Hyo , Park Ji-Hye , Park So-Jung
Published: June 2024

Objectives: The objective of this study was to explore the integration of Traditional Korean Medicine (TKM) into existing clinical pathways for the treatment of gastric cancer. focusing on enhancing treatment outcomes and improving patient quality of life.Methods: Employing a prospective observational design, the study targeted adults aged 20-75 diagnosed with gastric cancer. It assessed the TKM pathway's impact on quality of life, tumor markers, complete blood count test values, and patient satisfaction, and monitored adverse reactions to evaluate effectiveness and safety.Results: The study demonstrated improved quality of life(QOL), as indicated by increased Karnofsky Performance Scale(KPS) scores Mean Difference(MD)=20.37, and better quality of life (MD=19.79) assessments. Blood test results showed notable enhancements in immune function markers such as Neutrophil (MD=-7.34%) and Lymphocyte (6.80%), and Erythrocyte Sedimentation Rate (ESR)(MD=-11.05mm/hr). Both patient and medical staff satisfaction (MD=0.33) improved, although changes in tumor markers were not statistically significant.Conclusions: The integration of TKM into the treatment of gastric cancer can significantly improve patient quality of life and satisfaction. To further substantiate these results, developing and implementing more critical pathways across varied clinical settings, along with larger-scaled studies, are essential.
Survey of Korean Medicine Doctors Applying to Participate in the School Doctor Program of Korean Medicine
Authors: Park Jeong-Su , Lee Seung Hwan , Shin Seon Mi
Published: June 2024

Objectives: This study aimed to identify the current status, satisfaction, obstacles, and improvement points of the School Doctor Program of Korean Medicine, while providing supporting data for its enhancement.Methods: A self-reporting online survey was conducted among doctors of the Seoul Korean Medicine Association who applied to participate in the 2023 School Doctor Program of Korean Medicine. The questionnaire assessed various aspects including program status, satisfaction, evaluation, advantages, obstacles, promotion plans for the 2023 program, and intention to participate in the 2024 program. The survey was conducted from March 5th to 12th, 2024.Results: A total of 60 doctors participated in the survey, with 57 respondents included in the analysis. Among them, 45 Korean medical doctors had actively engaged in the school doctor program. Main reasons for non-participation included lack of request from assigned schools or scheduling conflicts between the desired program time and the conditions of Korean medicine doctors. Participants who conducted the program reported its effectiveness in fostering positive perceptions of Korean medicine. Despite obstacles, the majority expressed willingness to participate in the 2024 program. To promote the program, there is a need for a structured system to facilitate school cooperation and promote the School Doctor Program of Korean Medicine.Conclusions: Promoting the School Doctor Program of Korean Medicine requires collaboration from schools, provision of standardized manuals and programs, and support from the Korean Medicine Association. Strengthening systems for school cooperation and program promotion is essential for its advancement.